<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03808610</url>
  </required_header>
  <id_info>
    <org_study_id>2016-0629</org_study_id>
    <secondary_id>NCI-2018-03360</secondary_id>
    <secondary_id>2016-0629</secondary_id>
    <nct_id>NCT03808610</nct_id>
  </id_info>
  <brief_title>Low-Intensity Chemotherapy and Venetoclax in Treating Patients With Relapsed or Refractory B- or T-Cell Acute Lymphoblastic Leukemia</brief_title>
  <official_title>Phase I/II Study of the Combination of Low-Intensity Chemotherapy and Venetoclax (ABT-199) in Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>M.D. Anderson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>M.D. Anderson Cancer Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase I/II trial studies the side effects and best dose of venetoclax and how well it&#xD;
      works in combination with low-intensity chemotherapy in patients with B- or T-cell acute&#xD;
      lymphoblastic leukemia that has not responded to treatment or that has come back. Venetoclax&#xD;
      may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.&#xD;
      Drugs used in chemotherapy, including vincristine, cyclophosphamide, dexamethasone,&#xD;
      rituximab, methotrexate, and cytarabine, work in different ways to stop the growth of tumor&#xD;
      cells, either by killing the cells, by stopping them from dividing, or by stopping them from&#xD;
      spreading. Giving venetoclax with low-intensity chemotherapy may work better in treating&#xD;
      patient with B- or T-cell acute lymphoblastic leukemia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. Determine the maximum tolerated dose (MTD) and dose-limited toxicities (DLTs) of&#xD;
      venetoclax in combination with low-intensity chemotherapy in patients with&#xD;
      relapsed/refractory acute lymphoblastic leukemia (ALL) (Phase I).&#xD;
&#xD;
      II. Evaluate the overall response rate (complete response [CR] + CR with inadequate count&#xD;
      recovery [CRi]) of the regimen after 2 cycles. (Phase II)&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. Evaluate other clinical efficacy endpoints (minimal residual disease [MRD] negativity,&#xD;
      duration of response [DOR], event-free survival [EFS] and overall survival [OS]).&#xD;
&#xD;
      II. Determine the safety of the combination regimen.&#xD;
&#xD;
      EXPLORATORY OBJECTIVES:&#xD;
&#xD;
      I. To correlate apoptotic protein expression and Bcl-2 dependency on response and resistance&#xD;
      to the combination regimen.&#xD;
&#xD;
      OUTLINE: This is a phase I, dose-escalation study of venetoclax, followed by a phase II&#xD;
      study.&#xD;
&#xD;
      CHEMOTHERAPY AND VENETOCLAX:&#xD;
&#xD;
      CYCLE 1: Patients receive venetoclax orally (PO) once daily (QD) on days 1-21, vincristine&#xD;
      intravenously (IV) over 15 minutes on days 7 and 17, cyclophosphamide IV twice daily (BID)&#xD;
      over 3 hours on days 7-9, and dexamethasone IV over 30 minutes or PO QD on days 7-10 and&#xD;
      17-20. Patients may also receive rituximab IV over 4-6 hours on days 7 and 17 per physician&#xD;
      discretion.&#xD;
&#xD;
      CYCLES 2, 4, 6, and 8: Patients receive venetoclax PO QD on days 1-21, methotrexate IV over&#xD;
      24 hours on day 1, and cytarabine IV BID over 3 hours on days 2 and 3. Patients may also&#xD;
      receive rituximab IV over 4-6 hours on days 1 and 8 per physician discretion.&#xD;
&#xD;
      CYCLES 3, 5, and 7: Patients receive venetoclax PO QD on days 1-21, cyclophosphamide IV BID&#xD;
      over 3 hours on days 1-3, vincristine IV over 15 minutes on days 1 and 11, and dexamethasone&#xD;
      IV over 30 minutes or PO QD on days 1-4 and 11-14. Patients may also receive rituximab IV&#xD;
      over 4-6 hours on days 1 and 11 per physician discretion.&#xD;
&#xD;
      T-CELL ALL: After the first 4 cycles, patients receive nelarabine IV over 2 hours on days 1-5&#xD;
      and pegaspargase IV over 2 hours on day 5. Cycles repeat every 28 days for 2 cycles (after&#xD;
      cycle 4 and 5) in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      MAINTENANCE THERAPY: Patients may receive prednisone PO QD on days 1-5, vincristine IV over&#xD;
      15 minutes on day 1, and venetoclax, PO QD on days 1-21. Cycles repeat every 28 days for 2&#xD;
      years in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      T-CELL ALL (MAINTENANCE THERAPY): After the first 5 cycles of maintenance therapy, patients&#xD;
      who received nelarabine and pegaspargase will receive nelarabine IV QD over 2 hours on days&#xD;
      1-5 and pegaspargase IV over 2 hours on day 5 during maintenance cycles 6 and 7 instead of&#xD;
      prednisone, vincristine, and venetoclax.&#xD;
&#xD;
      After completion of study treatment, patients are followed up for 30 days and then every 3&#xD;
      months thereafter.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 3, 2019</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum tolerated dose (MTD) (Phase I)</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>The MTD is the highest dose level in which &lt; 2 patients of 6 develop first cycle dose-limiting toxicity (DLT).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>DLT (Phase I)</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>A non-hematologic DLT is defined as a clinically significant (as assessed by treating physician) grade 3 or 4 adverse event or abnormal laboratory value (according to Common Terminology Criteria for Adverse Events [CTCAE] criteria). Toxicity type, severity and attribution will be summarized for each patient using frequency tables.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall response rate (Phase II)</measure>
    <time_frame>Up to 56 days (2 courses)</time_frame>
    <description>Will be defined as the percentage of patients achieving a complete response (CR) or CR with inadequate count recovery (CRi). Will estimate the overall response (OR) for the combination treatment, along with the 95% credible interval.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimal residual disease (MRD) negativity</measure>
    <time_frame>Up to 4 years</time_frame>
    <description>Will be summarized using descriptive statistics such as mean, standard deviation, median and range.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DOR)</measure>
    <time_frame>Up to 4 years</time_frame>
    <description>Will be summarized using descriptive statistics such as mean, standard deviation, median and range. The association between response and patient's clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test, as appropriate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Event-free survival (EFS)</measure>
    <time_frame>From the first day of treatment until any failure (resistant disease, relapse, or death), assessed up to 4 years</time_frame>
    <description>The association between response and patient's clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test, as appropriate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>From the first day of treatment to time of death from any cause, assessed up to 4 years</time_frame>
    <description>The association between response and patient's clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test, as appropriate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events</measure>
    <time_frame>Up to 4 years</time_frame>
    <description>Will be summarized using descriptive statistics such as mean, standard deviation, median and range.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Apoptotic protein expression and Bcl-2 dependency</measure>
    <time_frame>Up to 4 years</time_frame>
    <description>Apoptotic protein expression and Bcl-2 dependency will be correlated on response and resistance to the combination regimen.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Recurrent B Acute Lymphoblastic Leukemia</condition>
  <condition>Recurrent T Acute Lymphoblastic Leukemia</condition>
  <condition>Refractory B Acute Lymphoblastic Leukemia</condition>
  <condition>Refractory T Acute Lymphoblastic Leukemia</condition>
  <arm_group>
    <arm_group_label>Experimental (venetoclax, vincristine, cyclophosphamide)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>See Detailed Description.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Experimental (venetoclax, vincristine, cyclophosphamide)</arm_group_label>
    <other_name>(-)-Cyclophosphamide</other_name>
    <other_name>2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate</other_name>
    <other_name>Carloxan</other_name>
    <other_name>Ciclofosfamida</other_name>
    <other_name>Ciclofosfamide</other_name>
    <other_name>Cicloxal</other_name>
    <other_name>Clafen</other_name>
    <other_name>Claphene</other_name>
    <other_name>CP monohydrate</other_name>
    <other_name>CTX</other_name>
    <other_name>CYCLO-cell</other_name>
    <other_name>Cycloblastin</other_name>
    <other_name>Cycloblastine</other_name>
    <other_name>Cyclophospham</other_name>
    <other_name>Cyclophosphamid monohydrate</other_name>
    <other_name>Cyclophosphamidum</other_name>
    <other_name>Cyclophosphan</other_name>
    <other_name>Cyclophosphane</other_name>
    <other_name>Cyclophosphanum</other_name>
    <other_name>Cyclostin</other_name>
    <other_name>Cyclostine</other_name>
    <other_name>Cytophosphan</other_name>
    <other_name>Cytophosphane</other_name>
    <other_name>Cytoxan</other_name>
    <other_name>Fosfaseron</other_name>
    <other_name>Genoxal</other_name>
    <other_name>Genuxal</other_name>
    <other_name>Ledoxina</other_name>
    <other_name>Mitoxan</other_name>
    <other_name>Neosar</other_name>
    <other_name>Revimmune</other_name>
    <other_name>Syklofosfamid</other_name>
    <other_name>WR- 138719</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cytarabine</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Experimental (venetoclax, vincristine, cyclophosphamide)</arm_group_label>
    <other_name>.beta.-Cytosine arabinoside</other_name>
    <other_name>1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone</other_name>
    <other_name>1-.beta.-D-Arabinofuranosylcytosine</other_name>
    <other_name>1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone</other_name>
    <other_name>1-Beta-D-arabinofuranosylcytosine</other_name>
    <other_name>1.beta.-D-Arabinofuranosylcytosine</other_name>
    <other_name>2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-</other_name>
    <other_name>2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-</other_name>
    <other_name>Alexan</other_name>
    <other_name>Ara-C</other_name>
    <other_name>ARA-cell</other_name>
    <other_name>Arabine</other_name>
    <other_name>Arabinofuranosylcytosine</other_name>
    <other_name>Arabinosylcytosine</other_name>
    <other_name>Aracytidine</other_name>
    <other_name>Aracytin</other_name>
    <other_name>Aracytine</other_name>
    <other_name>Beta-cytosine Arabinoside</other_name>
    <other_name>CHX-3311</other_name>
    <other_name>Cytarabinum</other_name>
    <other_name>Cytarbel</other_name>
    <other_name>Cytosar</other_name>
    <other_name>Cytosine Arabinoside</other_name>
    <other_name>Cytosine-.beta.-arabinoside</other_name>
    <other_name>Cytosine-beta-arabinoside</other_name>
    <other_name>Erpalfa</other_name>
    <other_name>Starasid</other_name>
    <other_name>Tarabine PFS</other_name>
    <other_name>U 19920</other_name>
    <other_name>U-19920</other_name>
    <other_name>Udicil</other_name>
    <other_name>WR-28453</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <description>Given IV or PO</description>
    <arm_group_label>Experimental (venetoclax, vincristine, cyclophosphamide)</arm_group_label>
    <other_name>Aacidexam</other_name>
    <other_name>Adexone</other_name>
    <other_name>Aknichthol Dexa</other_name>
    <other_name>Alba-Dex</other_name>
    <other_name>Alin</other_name>
    <other_name>Alin Depot</other_name>
    <other_name>Alin Oftalmico</other_name>
    <other_name>Amplidermis</other_name>
    <other_name>Anemul mono</other_name>
    <other_name>Auricularum</other_name>
    <other_name>Auxiloson</other_name>
    <other_name>Baycadron</other_name>
    <other_name>Baycuten</other_name>
    <other_name>Baycuten N</other_name>
    <other_name>Cortidexason</other_name>
    <other_name>Cortisumman</other_name>
    <other_name>Decacort</other_name>
    <other_name>Decadrol</other_name>
    <other_name>Decadron</other_name>
    <other_name>Decadron DP</other_name>
    <other_name>Decalix</other_name>
    <other_name>Decameth</other_name>
    <other_name>Decasone R.p.</other_name>
    <other_name>Dectancyl</other_name>
    <other_name>Dekacort</other_name>
    <other_name>Deltafluorene</other_name>
    <other_name>Deronil</other_name>
    <other_name>Desamethasone</other_name>
    <other_name>Desameton</other_name>
    <other_name>Dexa-Mamallet</other_name>
    <other_name>Dexa-Rhinosan</other_name>
    <other_name>Dexa-Scheroson</other_name>
    <other_name>Dexa-sine</other_name>
    <other_name>Dexacortal</other_name>
    <other_name>Dexacortin</other_name>
    <other_name>Dexafarma</other_name>
    <other_name>Dexafluorene</other_name>
    <other_name>Dexalocal</other_name>
    <other_name>Dexamecortin</other_name>
    <other_name>Dexameth</other_name>
    <other_name>Dexamethasone Intensol</other_name>
    <other_name>Dexamethasonum</other_name>
    <other_name>Dexamonozon</other_name>
    <other_name>Dexapos</other_name>
    <other_name>Dexinoral</other_name>
    <other_name>Dexone</other_name>
    <other_name>Dinormon</other_name>
    <other_name>Fluorodelta</other_name>
    <other_name>Fortecortin</other_name>
    <other_name>Gammacorten</other_name>
    <other_name>Hexadecadrol</other_name>
    <other_name>Hexadrol</other_name>
    <other_name>Lokalison-F</other_name>
    <other_name>Loverine</other_name>
    <other_name>Methylfluorprednisolone</other_name>
    <other_name>Millicorten</other_name>
    <other_name>Mymethasone</other_name>
    <other_name>Orgadrone</other_name>
    <other_name>Spersadex</other_name>
    <other_name>TaperDex</other_name>
    <other_name>Visumetazone</other_name>
    <other_name>ZoDex</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methotrexate</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Experimental (venetoclax, vincristine, cyclophosphamide)</arm_group_label>
    <other_name>Abitrexate</other_name>
    <other_name>Alpha-Methopterin</other_name>
    <other_name>Amethopterin</other_name>
    <other_name>Brimexate</other_name>
    <other_name>CL 14377</other_name>
    <other_name>CL-14377</other_name>
    <other_name>Emtexate</other_name>
    <other_name>Emthexat</other_name>
    <other_name>Emthexate</other_name>
    <other_name>Farmitrexat</other_name>
    <other_name>Fauldexato</other_name>
    <other_name>Folex</other_name>
    <other_name>Folex PFS</other_name>
    <other_name>Lantarel</other_name>
    <other_name>Ledertrexate</other_name>
    <other_name>Lumexon</other_name>
    <other_name>Maxtrex</other_name>
    <other_name>Medsatrexate</other_name>
    <other_name>Metex</other_name>
    <other_name>Methoblastin</other_name>
    <other_name>Methotrexate LPF</other_name>
    <other_name>Methotrexate Methylaminopterin</other_name>
    <other_name>Methotrexatum</other_name>
    <other_name>Metotrexato</other_name>
    <other_name>Metrotex</other_name>
    <other_name>Mexate</other_name>
    <other_name>Mexate-AQ</other_name>
    <other_name>MTX</other_name>
    <other_name>Novatrex</other_name>
    <other_name>Rheumatrex</other_name>
    <other_name>Texate</other_name>
    <other_name>Tremetex</other_name>
    <other_name>Trexeron</other_name>
    <other_name>Trixilem</other_name>
    <other_name>WR-19039</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nelarabine</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Experimental (venetoclax, vincristine, cyclophosphamide)</arm_group_label>
    <other_name>2-Amino-6-methoxypurine arabinoside</other_name>
    <other_name>506U78</other_name>
    <other_name>Arranon</other_name>
    <other_name>Compound 506U78</other_name>
    <other_name>GW506U78</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pegaspargase</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Experimental (venetoclax, vincristine, cyclophosphamide)</arm_group_label>
    <other_name>L-Asparaginase with Polyethylene Glycol</other_name>
    <other_name>Oncaspar</other_name>
    <other_name>Oncaspar-IV</other_name>
    <other_name>PEG-Asparaginase</other_name>
    <other_name>PEG-L-Asparaginase</other_name>
    <other_name>PEG-L-Asparaginase (Enzon - Kyowa Hakko)</other_name>
    <other_name>PEGLA</other_name>
    <other_name>Polyethylene Glycol L-Asparaginase</other_name>
    <other_name>Polyethylene Glycol-L-Asparaginase</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prednisone</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Experimental (venetoclax, vincristine, cyclophosphamide)</arm_group_label>
    <other_name>.delta.1-Cortisone</other_name>
    <other_name>1, 2-Dehydrocortisone</other_name>
    <other_name>Adasone</other_name>
    <other_name>Cortancyl</other_name>
    <other_name>Dacortin</other_name>
    <other_name>DeCortin</other_name>
    <other_name>Decortisyl</other_name>
    <other_name>Decorton</other_name>
    <other_name>Delta 1-Cortisone</other_name>
    <other_name>Delta-Dome</other_name>
    <other_name>Deltacortene</other_name>
    <other_name>Deltacortisone</other_name>
    <other_name>Deltadehydrocortisone</other_name>
    <other_name>Deltasone</other_name>
    <other_name>Deltison</other_name>
    <other_name>Deltra</other_name>
    <other_name>Econosone</other_name>
    <other_name>Lisacort</other_name>
    <other_name>Meprosona-F</other_name>
    <other_name>Metacortandracin</other_name>
    <other_name>Meticorten</other_name>
    <other_name>Ofisolona</other_name>
    <other_name>Orasone</other_name>
    <other_name>Panafcort</other_name>
    <other_name>Panasol-S</other_name>
    <other_name>Paracort</other_name>
    <other_name>Perrigo Prednisone</other_name>
    <other_name>PRED</other_name>
    <other_name>Predicor</other_name>
    <other_name>Predicorten</other_name>
    <other_name>Prednicen-M</other_name>
    <other_name>Prednicort</other_name>
    <other_name>Prednidib</other_name>
    <other_name>Prednilonga</other_name>
    <other_name>Predniment</other_name>
    <other_name>Prednisone Intensol</other_name>
    <other_name>Prednisonum</other_name>
    <other_name>Prednitone</other_name>
    <other_name>Promifen</other_name>
    <other_name>Rayos</other_name>
    <other_name>Servisone</other_name>
    <other_name>SK-Prednisone</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Rituximab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Experimental (venetoclax, vincristine, cyclophosphamide)</arm_group_label>
    <other_name>ABP 798</other_name>
    <other_name>BI 695500</other_name>
    <other_name>C2B8 Monoclonal Antibody</other_name>
    <other_name>Chimeric Anti-CD20 Antibody</other_name>
    <other_name>CT-P10</other_name>
    <other_name>IDEC-102</other_name>
    <other_name>IDEC-C2B8</other_name>
    <other_name>IDEC-C2B8 Monoclonal Antibody</other_name>
    <other_name>MabThera</other_name>
    <other_name>Monoclonal Antibody IDEC-C2B8</other_name>
    <other_name>PF-05280586</other_name>
    <other_name>Rituxan</other_name>
    <other_name>Rituximab Biosimilar ABP 798</other_name>
    <other_name>Rituximab Biosimilar BI 695500</other_name>
    <other_name>Rituximab Biosimilar CT-P10</other_name>
    <other_name>Rituximab Biosimilar GB241</other_name>
    <other_name>Rituximab Biosimilar IBI301</other_name>
    <other_name>Rituximab Biosimilar PF-05280586</other_name>
    <other_name>Rituximab Biosimilar RTXM83</other_name>
    <other_name>Rituximab Biosimilar SAIT101</other_name>
    <other_name>rituximab biosimilar TQB2303</other_name>
    <other_name>rituximab-abbs</other_name>
    <other_name>RTXM83</other_name>
    <other_name>Truxima</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Venetoclax</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Experimental (venetoclax, vincristine, cyclophosphamide)</arm_group_label>
    <other_name>ABT-0199</other_name>
    <other_name>ABT-199</other_name>
    <other_name>ABT199</other_name>
    <other_name>GDC-0199</other_name>
    <other_name>RG7601</other_name>
    <other_name>Venclexta</other_name>
    <other_name>Venclyxto</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vincristine</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Experimental (venetoclax, vincristine, cyclophosphamide)</arm_group_label>
    <other_name>LEUROCRISTINE</other_name>
    <other_name>VCR</other_name>
    <other_name>Vincrystine</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with relapsed/refractory B- or T-cell ALL&#xD;
&#xD;
          -  Performance status =&lt; 3 (Eastern Cooperative Oncology Group [ECOG] Scale)&#xD;
&#xD;
          -  Total serum bilirubin =&lt; 2 x upper limit of normal (ULN), unless due to Gilbert's&#xD;
             syndrome, in which case patients are eligible as long as direct bilirubin =&lt; 2 x ULN&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) =&lt; 3 x ULN, unless due to disease involvement of the&#xD;
             liver or hemolysis, in which case an ALT =&lt; 10 x ULN is acceptable&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) =&lt; 3 x ULN, unless due to disease involvement of the&#xD;
             liver or hemolysis, in which case an AST =&lt; 10 x ULN is acceptable&#xD;
&#xD;
          -  Creatinine clearance &gt;= 30 mL/min&#xD;
&#xD;
          -  For females of childbearing potential, a negative pregnancy test must be documented&#xD;
             within 1 week of starting treatment&#xD;
&#xD;
          -  Female and male patients who are fertile must agree to use an effective form of&#xD;
             contraception (birth control methods while on study, such as birth control pills or&#xD;
             injections, intrauterine devices [IUDs]), or double-barrier methods (for example, a&#xD;
             condom in combination with spermicide) with their sexual partners for 4 months after&#xD;
             the end of treatment&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with Philadelphia chromosome-positive ALL or Burkitt leukemia&#xD;
&#xD;
          -  Active serious infection not controlled by oral or intravenous antibiotics&#xD;
&#xD;
          -  Active secondary malignancy other than skin cancer (e.g., basal cell carcinoma or&#xD;
             squamous cell carcinoma) that in the investigator's opinion will shorten survival to&#xD;
             less than 1 year&#xD;
&#xD;
          -  Known hepatitis B or C infection, or known seropositivity for human immunodeficiency&#xD;
             virus (HIV)&#xD;
&#xD;
          -  Active grade III-V cardiac failure as defined by the New York Heart Association&#xD;
             Criteria&#xD;
&#xD;
          -  Patients with a cardiac ejection fraction (as measured by either multigated&#xD;
             acquisition [MUGA] or echocardiogram) &lt; 40%&#xD;
&#xD;
          -  Received moderate or strong CYP3A inhibitors or strong CYP3A inducers within 7 days of&#xD;
             starting venetoclax&#xD;
&#xD;
          -  Consumed grapefruit, grapefruit products, Seville oranges, or star fruit within 3 days&#xD;
             prior to starting venetoclax&#xD;
&#xD;
          -  Prior history of treatment with venetoclax&#xD;
&#xD;
          -  Treatment with any investigational antileukemic agents or chemotherapy agents in the&#xD;
             last 7 days before study entry, unless full recovery from side effects has occurred or&#xD;
             patient has rapidly progressive disease judged to be life-threatening by the&#xD;
             investigator. Exception: Treatment with hydroxyurea and/or dexamethasone are allowed&#xD;
             prior to study treatment, without window of exclusion&#xD;
&#xD;
          -  Pregnant and lactating women will not be eligible; women of childbearing potential&#xD;
             should have a negative pregnancy test prior to entering on the study and be willing to&#xD;
             practice methods of contraception. Women do not have childbearing potential if they&#xD;
             have had a hysterectomy or are postmenopausal without menses for 12 months. In&#xD;
             addition, men enrolled on this study should understand the risks to any sexual partner&#xD;
             of childbearing potential and should practice an effective method of birth control&#xD;
&#xD;
          -  History of significant bleeding disorder unrelated to cancer, including: diagnosed&#xD;
             congenital bleeding disorders (e.g., von Willebrand's disease); diagnosed acquired&#xD;
             bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Elias Jabbour</last_name>
    <role>Principal Investigator</role>
    <affiliation>M.D. Anderson Cancer Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Elias Jabbour</last_name>
    <phone>713-792-4764</phone>
    <email>ejabbour@mdanderson.org</email>
  </overall_contact>
  <location>
    <facility>
      <name>M D Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Elias Jabbour</last_name>
      <phone>713-792-4764</phone>
    </contact>
    <investigator>
      <last_name>Elias Jabbour</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mdanderson.org</url>
    <description>MD Anderson Cancer Center</description>
  </link>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>January 16, 2019</study_first_submitted>
  <study_first_submitted_qc>January 16, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 17, 2019</study_first_posted>
  <last_update_submitted>June 12, 2023</last_update_submitted>
  <last_update_submitted_qc>June 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 15, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
    <mesh_term>Leukemia, Lymphoid</mesh_term>
    <mesh_term>Precursor T-Cell Lymphoblastic Leukemia-Lymphoma</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cytarabine</mesh_term>
    <mesh_term>6-methoxypurine arabinoside</mesh_term>
    <mesh_term>Dexamethasone</mesh_term>
    <mesh_term>Dexamethasone acetate</mesh_term>
    <mesh_term>Prednisone</mesh_term>
    <mesh_term>Cortisone</mesh_term>
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Rituximab</mesh_term>
    <mesh_term>Methotrexate</mesh_term>
    <mesh_term>Vincristine</mesh_term>
    <mesh_term>Venetoclax</mesh_term>
    <mesh_term>Asparaginase</mesh_term>
    <mesh_term>Pegaspargase</mesh_term>
    <mesh_term>Antineoplastic Agents, Immunological</mesh_term>
    <mesh_term>Antibodies</mesh_term>
    <mesh_term>Immunoglobulins</mesh_term>
    <mesh_term>Antibodies, Monoclonal</mesh_term>
    <mesh_term>BB 1101</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03808610
org study id: 2016-0629
secondary id: NCI-2018-03360
secondary id: 2016-0629
nct id: NCT03808610
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This phase I/II trial studies the side effects and best dose of venetoclax and how well it
      works in combination with low-intensity chemotherapy in patients with B- or T-cell acute
      lymphoblastic leukemia that has not responded to treatment or that has come back. Venetoclax
      may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
      Drugs used in chemotherapy, including vincristine, cyclophosphamide, dexamethasone,
      rituximab, methotrexate, and cytarabine, work in different ways to stop the growth of tumor
      cells, either by killing the cells, by stopping them from dividing, or by stopping them from
      spreading. Giving venetoclax with low-intensity chemotherapy may work better in treating
      patient with B- or T-cell acute lymphoblastic leukemia.
PRIMARY OBJECTIVES:

      I. Determine the maximum tolerated dose (MTD) and dose-limited toxicities (DLTs) of
      venetoclax in combination with low-intensity chemotherapy in patients with
      relapsed/refractory acute lymphoblastic leukemia (ALL) (Phase I).

      II. Evaluate the overall response rate (complete response [CR] + CR with inadequate count
      recovery [CRi]) of the regimen after 2 cycles. (Phase II)

      SECONDARY OBJECTIVES:

      I. Evaluate other clinical efficacy endpoints (minimal residual disease [MRD] negativity,
      duration of response [DOR], event-free survival [EFS] and overall survival [OS]).

      II. Determine the safety of the combination regimen.

      EXPLORATORY OBJECTIVES:

      I. To correlate apoptotic protein expression and Bcl-2 dependency on response and resistance
      to the combination regimen.

      OUTLINE: This is a phase I, dose-escalation study of venetoclax, followed by a phase II
      study.

      CHEMOTHERAPY AND VENETOCLAX:

      CYCLE 1: Patients receive venetoclax orally (PO) once daily (QD) on days 1-21, vincristine
      intravenously (IV) over 15 minutes on days 7 and 17, cyclophosphamide IV twice daily (BID)
      over 3 hours on days 7-9, and dexamethasone IV over 30 minutes or PO QD on days 7-10 and
      17-20. Patients may also receive rituximab IV over 4-6 hours on days 7 and 17 per physician
      discretion.

      CYCLES 2, 4, 6, and 8: Patients receive venetoclax PO QD on days 1-21, methotrexate IV over
      24 hours on day 1, and cytarabine IV BID over 3 hours on days 2 and 3. Patients may also
      receive rituximab IV over 4-6 hours on days 1 and 8 per physician discretion.

      CYCLES 3, 5, and 7: Patients receive venetoclax PO QD on days 1-21, cyclophosphamide IV BID
      over 3 hours on days 1-3, vincristine IV over 15 minutes on days 1 and 11, and dexamethasone
      IV over 30 minutes or PO QD on days 1-4 and 11-14. Patients may also receive rituximab IV
      over 4-6 hours on days 1 and 11 per physician discretion.

      T-CELL ALL: After the first 4 cycles, patients receive nelarabine IV over 2 hours on days 1-5
      and pegaspargase IV over 2 hours on day 5. Cycles repeat every 28 days for 2 cycles (after
      cycle 4 and 5) in the absence of disease progression or unacceptable toxicity.

      MAINTENANCE THERAPY: Patients may receive prednisone PO QD on days 1-5, vincristine IV over
      15 minutes on day 1, and venetoclax, PO QD on days 1-21. Cycles repeat every 28 days for 2
      years in the absence of disease progression or unacceptable toxicity.

      T-CELL ALL (MAINTENANCE THERAPY): After the first 5 cycles of maintenance therapy, patients
      who received nelarabine and pegaspargase will receive nelarabine IV QD over 2 hours on days
      1-5 and pegaspargase IV over 2 hours on day 5 during maintenance cycles 6 and 7 instead of
      prednisone, vincristine, and venetoclax.

      After completion of study treatment, patients are followed up for 30 days and then every 3
      months thereafter.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum tolerated dose (MTD) (Phase I)
time frame: Up to 28 days
description: The MTD is the highest dose level in which < 2 patients of 6 develop first cycle dose-limiting toxicity (DLT).
measure: DLT (Phase I)
time frame: Up to 28 days
description: A non-hematologic DLT is defined as a clinically significant (as assessed by treating physician) grade 3 or 4 adverse event or abnormal laboratory value (according to Common Terminology Criteria for Adverse Events [CTCAE] criteria). Toxicity type, severity and attribution will be summarized for each patient using frequency tables.
measure: Overall response rate (Phase II)
time frame: Up to 56 days (2 courses)
description: Will be defined as the percentage of patients achieving a complete response (CR) or CR with inadequate count recovery (CRi). Will estimate the overall response (OR) for the combination treatment, along with the 95% credible interval.
measure: Minimal residual disease (MRD) negativity
time frame: Up to 4 years
description: Will be summarized using descriptive statistics such as mean, standard deviation, median and range.
measure: Duration of response (DOR)
time frame: Up to 4 years
description: Will be summarized using descriptive statistics such as mean, standard deviation, median and range. The association between response and patient's clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test, as appropriate.
measure: Event-free survival (EFS)
time frame: From the first day of treatment until any failure (resistant disease, relapse, or death), assessed up to 4 years
description: The association between response and patient's clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test, as appropriate.
measure: Overall survival (OS)
time frame: From the first day of treatment to time of death from any cause, assessed up to 4 years
description: The association between response and patient's clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test, as appropriate.
measure: Incidence of adverse events
time frame: Up to 4 years
description: Will be summarized using descriptive statistics such as mean, standard deviation, median and range.
measure: Apoptotic protein expression and Bcl-2 dependency
time frame: Up to 4 years
description: Apoptotic protein expression and Bcl-2 dependency will be correlated on response and resistance to the combination regimen.
arm group label: Experimental (venetoclax, vincristine, cyclophosphamide)
arm group type: Experimental
description: See Detailed Description.
intervention type: Drug
intervention name: Cyclophosphamide
description: Given IV
arm group label: Experimental (venetoclax, vincristine, cyclophosphamide)
other name: (-)-Cyclophosphamide
other name: 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
other name: Carloxan
other name: Ciclofosfamida
other name: Ciclofosfamide
other name: Cicloxal
other name: Clafen
other name: Claphene
other name: CP monohydrate
other name: CTX
other name: CYCLO-cell
other name: Cycloblastin
other name: Cycloblastine
other name: Cyclophospham
other name: Cyclophosphamid monohydrate
other name: Cyclophosphamidum
other name: Cyclophosphan
other name: Cyclophosphane
other name: Cyclophosphanum
other name: Cyclostin
other name: Cyclostine
other name: Cytophosphan
other name: Cytophosphane
other name: Cytoxan
other name: Fosfaseron
other name: Genoxal
other name: Genuxal
other name: Ledoxina
other name: Mitoxan
other name: Neosar
other name: Revimmune
other name: Syklofosfamid
other name: WR- 138719
intervention type: Drug
intervention name: Cytarabine
description: Given IV
arm group label: Experimental (venetoclax, vincristine, cyclophosphamide)
other name: .beta.-Cytosine arabinoside
other name: 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone
other name: 1-.beta.-D-Arabinofuranosylcytosine
other name: 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone
other name: 1-Beta-D-arabinofuranosylcytosine
other name: 1.beta.-D-Arabinofuranosylcytosine
other name: 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-
other name: 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-
other name: Alexan
other name: Ara-C
other name: ARA-cell
other name: Arabine
other name: Arabinofuranosylcytosine
other name: Arabinosylcytosine
other name: Aracytidine
other name: Aracytin
other name: Aracytine
other name: Beta-cytosine Arabinoside
other name: CHX-3311
other name: Cytarabinum
other name: Cytarbel
other name: Cytosar
other name: Cytosine Arabinoside
other name: Cytosine-.beta.-arabinoside
other name: Cytosine-beta-arabinoside
other name: Erpalfa
other name: Starasid
other name: Tarabine PFS
other name: U 19920
other name: U-19920
other name: Udicil
other name: WR-28453
intervention type: Drug
intervention name: Dexamethasone
description: Given IV or PO
arm group label: Experimental (venetoclax, vincristine, cyclophosphamide)
other name: Aacidexam
other name: Adexone
other name: Aknichthol Dexa
other name: Alba-Dex
other name: Alin
other name: Alin Depot
other name: Alin Oftalmico
other name: Amplidermis
other name: Anemul mono
other name: Auricularum
other name: Auxiloson
other name: Baycadron
other name: Baycuten
other name: Baycuten N
other name: Cortidexason
other name: Cortisumman
other name: Decacort
other name: Decadrol
other name: Decadron
other name: Decadron DP
other name: Decalix
other name: Decameth
other name: Decasone R.p.
other name: Dectancyl
other name: Dekacort
other name: Deltafluorene
other name: Deronil
other name: Desamethasone
other name: Desameton
other name: Dexa-Mamallet
other name: Dexa-Rhinosan
other name: Dexa-Scheroson
other name: Dexa-sine
other name: Dexacortal
other name: Dexacortin
other name: Dexafarma
other name: Dexafluorene
other name: Dexalocal
other name: Dexamecortin
other name: Dexameth
other name: Dexamethasone Intensol
other name: Dexamethasonum
other name: Dexamonozon
other name: Dexapos
other name: Dexinoral
other name: Dexone
other name: Dinormon
other name: Fluorodelta
other name: Fortecortin
other name: Gammacorten
other name: Hexadecadrol
other name: Hexadrol
other name: Lokalison-F
other name: Loverine
other name: Methylfluorprednisolone
other name: Millicorten
other name: Mymethasone
other name: Orgadrone
other name: Spersadex
other name: TaperDex
other name: Visumetazone
other name: ZoDex
intervention type: Drug
intervention name: Methotrexate
description: Given IV
arm group label: Experimental (venetoclax, vincristine, cyclophosphamide)
other name: Abitrexate
other name: Alpha-Methopterin
other name: Amethopterin
other name: Brimexate
other name: CL 14377
other name: CL-14377
other name: Emtexate
other name: Emthexat
other name: Emthexate
other name: Farmitrexat
other name: Fauldexato
other name: Folex
other name: Folex PFS
other name: Lantarel
other name: Ledertrexate
other name: Lumexon
other name: Maxtrex
other name: Medsatrexate
other name: Metex
other name: Methoblastin
other name: Methotrexate LPF
other name: Methotrexate Methylaminopterin
other name: Methotrexatum
other name: Metotrexato
other name: Metrotex
other name: Mexate
other name: Mexate-AQ
other name: MTX
other name: Novatrex
other name: Rheumatrex
other name: Texate
other name: Tremetex
other name: Trexeron
other name: Trixilem
other name: WR-19039
intervention type: Drug
intervention name: Nelarabine
description: Given IV
arm group label: Experimental (venetoclax, vincristine, cyclophosphamide)
other name: 2-Amino-6-methoxypurine arabinoside
other name: 506U78
other name: Arranon
other name: Compound 506U78
other name: GW506U78
intervention type: Drug
intervention name: Pegaspargase
description: Given IV
arm group label: Experimental (venetoclax, vincristine, cyclophosphamide)
other name: L-Asparaginase with Polyethylene Glycol
other name: Oncaspar
other name: Oncaspar-IV
other name: PEG-Asparaginase
other name: PEG-L-Asparaginase
other name: PEG-L-Asparaginase (Enzon - Kyowa Hakko)
other name: PEGLA
other name: Polyethylene Glycol L-Asparaginase
other name: Polyethylene Glycol-L-Asparaginase
intervention type: Drug
intervention name: Prednisone
description: Given PO
arm group label: Experimental (venetoclax, vincristine, cyclophosphamide)
other name: .delta.1-Cortisone
other name: 1, 2-Dehydrocortisone
other name: Adasone
other name: Cortancyl
other name: Dacortin
other name: DeCortin
other name: Decortisyl
other name: Decorton
other name: Delta 1-Cortisone
other name: Delta-Dome
other name: Deltacortene
other name: Deltacortisone
other name: Deltadehydrocortisone
other name: Deltasone
other name: Deltison
other name: Deltra
other name: Econosone
other name: Lisacort
other name: Meprosona-F
other name: Metacortandracin
other name: Meticorten
other name: Ofisolona
other name: Orasone
other name: Panafcort
other name: Panasol-S
other name: Paracort
other name: Perrigo Prednisone
other name: PRED
other name: Predicor
other name: Predicorten
other name: Prednicen-M
other name: Prednicort
other name: Prednidib
other name: Prednilonga
other name: Predniment
other name: Prednisone Intensol
other name: Prednisonum
other name: Prednitone
other name: Promifen
other name: Rayos
other name: Servisone
other name: SK-Prednisone
intervention type: Biological
intervention name: Rituximab
description: Given IV
arm group label: Experimental (venetoclax, vincristine, cyclophosphamide)
other name: ABP 798
other name: BI 695500
other name: C2B8 Monoclonal Antibody
other name: Chimeric Anti-CD20 Antibody
other name: CT-P10
other name: IDEC-102
other name: IDEC-C2B8
other name: IDEC-C2B8 Monoclonal Antibody
other name: MabThera
other name: Monoclonal Antibody IDEC-C2B8
other name: PF-05280586
other name: Rituxan
other name: Rituximab Biosimilar ABP 798
other name: Rituximab Biosimilar BI 695500
other name: Rituximab Biosimilar CT-P10
other name: Rituximab Biosimilar GB241
other name: Rituximab Biosimilar IBI301
other name: Rituximab Biosimilar PF-05280586
other name: Rituximab Biosimilar RTXM83
other name: Rituximab Biosimilar SAIT101
other name: rituximab biosimilar TQB2303
other name: rituximab-abbs
other name: RTXM83
other name: Truxima
intervention type: Drug
intervention name: Venetoclax
description: Given PO
arm group label: Experimental (venetoclax, vincristine, cyclophosphamide)
other name: ABT-0199
other name: ABT-199
other name: ABT199
other name: GDC-0199
other name: RG7601
other name: Venclexta
other name: Venclyxto
intervention type: Drug
intervention name: Vincristine
description: Given IV
arm group label: Experimental (venetoclax, vincristine, cyclophosphamide)
other name: LEUROCRISTINE
other name: VCR
other name: Vincrystine
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Elias Jabbour
role: Principal Investigator
affiliation: M.D. Anderson Cancer Center
last name: Elias Jabbour
phone: 713-792-4764
email: ejabbour@mdanderson.org
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
url: http://www.mdanderson.org
description: MD Anderson Cancer Center
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Precursor Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Leukemia, Lymphoid
mesh term: Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
mesh term: Recurrence
mesh term: Cytarabine
mesh term: 6-methoxypurine arabinoside
mesh term: Dexamethasone
mesh term: Dexamethasone acetate
mesh term: Prednisone
mesh term: Cortisone
mesh term: Cyclophosphamide
mesh term: Rituximab
mesh term: Methotrexate
mesh term: Vincristine
mesh term: Venetoclax
mesh term: Asparaginase
mesh term: Pegaspargase
mesh term: Antineoplastic Agents, Immunological
mesh term: Antibodies
mesh term: Immunoglobulins
mesh term: Antibodies, Monoclonal
mesh term: BB 1101