<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/NCT01664910</url>
  </required_header>
  <id_info>
    <org_study_id>2012-0265</org_study_id>
    <secondary_id>NCI-2012-02072</secondary_id>
    <secondary_id>2012-0265</secondary_id>
    <nct_id>NCT01664910</nct_id>
  </id_info>
  <brief_title>CMC-544 and Allogeneic Transplantation for CD22 Positive-Lymphoid Malignancies</brief_title>
  <official_title>Anti-CD22 Immunoconjugate Inotuzumab Ozogamicin (CMC-544) Added to Fludarabine, Bendamustine and Rituximab and Allogeneic Transplantation for CD22 Positive-Lymphoid Malignancies</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 the best dose of inotuzumab ozogamicin&#xD;
      when given together with fludarabine phosphate, bendamustine hydrochloride, and rituximab&#xD;
      before donor stem cell transplant in treating patients with lymphoid malignancies. Giving&#xD;
      chemotherapy drugs, such as fludarabine phosphate and bendamustine hydrochloride, before a&#xD;
      donor peripheral blood stem cell transplant helps stop the growth of cancer cells or abnormal&#xD;
      cell and helps stop the patient's immune system from rejecting the donor's stem cells.&#xD;
      Immunotherapy with monoclonal antibodies, such as inotuzumab ozogamicin and rituximab, may&#xD;
      help the body's immune system attack the cancer, and may interfere with the ability of tumor&#xD;
      cells to grow and spread. When the healthy stem cells from a donor are infused into the&#xD;
      patient they may help the patient's bone marrow make stem cells, red blood cells, white blood&#xD;
      cells, and platelets. Sometimes the transplanted cell from a donor can make an immune system&#xD;
      response against the body's normal cells. Giving fludarabine phosphate and bendamustine&#xD;
      hydrochloride before the transplant together with anti-thymocyte globulin and tacrolimus may&#xD;
      stop this from happening.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To characterize the safety of anti-cluster of differentiation (CD) 22 immunoconjugate&#xD;
      inotuzumab ozogamicin (CMC-544), when administered in conjunction with fludarabine&#xD;
      (fludarabine phosphate), bendamustine (bendamustine hydrochloride), and rituximab as&#xD;
      non-myeloablative preparative regimen for allogeneic stem cell transplantation for&#xD;
      CD22-positive lymphoid malignancies.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To estimate tumor response. II. To determine overall and event-free survival rates by&#xD;
      histology subtype.&#xD;
&#xD;
      OUTLINE: This is a dose-escalation study of inotuzumab ozogamicin.&#xD;
&#xD;
      Patients receive inotuzumab ozogamicin intravenously (IV) over 1 hour on day -13, and&#xD;
      fludarabine phosphate IV over 1 hour and bendamustine hydrochloride IV over 30 minutes to 1&#xD;
      hour on days -5 to -3. Patients with CD20-positive disease also receive rituximab IV over 4-6&#xD;
      hours on days -6, 1, and 8 and patients with matched unrelated donors (MUD) receive&#xD;
      anti-thymocyte globulin IV over 3-4 hours on days -2 to -1. All patients also receive&#xD;
      tacrolimus IV over 24 hours continuously or orally (PO) daily beginning on days -2 to 180&#xD;
      followed by taper in the absence of graft-versus-host disease (GVHD) and methotrexate IV over&#xD;
      30 minutes on days 1, 3, and 6 (1, 3, 6, and 11 in patients with MUD). Patients undergo&#xD;
      allogeneic bone marrow (BM) or peripheral blood stem cell (PBSC) transplant on day 0.&#xD;
&#xD;
      After completion of study treatment, patients are followed up periodically.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 29, 2012</start_date>
  <completion_date type="Actual">June 28, 2023</completion_date>
  <primary_completion_date type="Actual">June 28, 2023</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <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) of inotuzumab ozogamicin</measure>
    <time_frame>Up to 30 days</time_frame>
    <description>Defined as the highest dose for which the probability of toxicity is closest to 30%.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of dose-limiting toxicity</measure>
    <time_frame>Up to 30 days</time_frame>
    <description>Defined as grade III or IV renal, hepatic, intestinal, neurologic, pulmonary or cardiac adverse events, as well as graft failure or death at any time.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective overall response (complete remission and partial remission)</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Estimated with a 95% confidence interval in the dose that is declared the MTD. Logistic regression will be used to assess the association between response and disease and clinical characteristics of interest.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Kaplan-Meier survival curves will be used to estimate OS. Cox proportional hazards regression methodology will be used to assess the association between disease and clinical characteristics and the survival outcomes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Recurrence-free survival</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Kaplan-Meier survival curves will be used to estimate recurrence-free survival. Cox proportional hazards regression methodology will be used to assess the association between disease and clinical characteristics and the survival outcomes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative incidence of acute and chronic graft versus host disease (GVHD)</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>The method of Gooley et al will be used to estimate the cumulative incidence of acute and chronic GVHD.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">27</enrollment>
  <condition>Hematopoietic and Lymphoid Cell Neoplasm</condition>
  <arm_group>
    <arm_group_label>Treatment (transplant)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive inotuzumab ozogamicin IV over 1 hour on day -13, and fludarabine phosphate IV over 1 hour and bendamustine hydrochloride IV over 30 minutes to 1 hour on days -5 to -3. Patients with CD20-positive disease also receive rituximab IV over 4-6 hours on days -6, 1, and 8 and patients with MUD receive anti-thymocyte globulin IV over 3-4 hours on days -2 to -1. All patients also receive tacrolimus IV over 24 hours continuously or PO daily beginning on days -2 to 180 followed by taper in the absence of GVHD and methotrexate IV over 30 minutes on days 1, 3, and 6 (1, 3, 6, and 11 in patients with MUD). Patients undergo allogeneic BM or PBSC transplant on day 0.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Allogeneic Bone Marrow Transplantation</intervention_name>
    <description>Undergo allogeneic BM transplant</description>
    <arm_group_label>Treatment (transplant)</arm_group_label>
    <other_name>Allo BMT</other_name>
    <other_name>Allogeneic BMT</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Allogeneic Hematopoietic Stem Cell Transplantation</intervention_name>
    <description>Undergo allogeneic PBSC or BM transplant</description>
    <arm_group_label>Treatment (transplant)</arm_group_label>
    <other_name>Allogeneic Hematopoietic Cell Transplantation</other_name>
    <other_name>Allogeneic Stem Cell Transplantation</other_name>
    <other_name>HSC</other_name>
    <other_name>HSCT</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Anti-Thymocyte Globulin</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (transplant)</arm_group_label>
    <other_name>Antithymocyte Globulin</other_name>
    <other_name>Antithymocyte Serum</other_name>
    <other_name>ATG</other_name>
    <other_name>ATGAM</other_name>
    <other_name>ATS</other_name>
    <other_name>Thymoglobulin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bendamustine Hydrochloride</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (transplant)</arm_group_label>
    <other_name>Bendamustin Hydrochloride</other_name>
    <other_name>Cytostasan Hydrochloride</other_name>
    <other_name>Levact</other_name>
    <other_name>Ribomustin</other_name>
    <other_name>SyB L-0501</other_name>
    <other_name>Treanda</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fludarabine Phosphate</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (transplant)</arm_group_label>
    <other_name>2-F-ara-AMP</other_name>
    <other_name>9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-</other_name>
    <other_name>Beneflur</other_name>
    <other_name>Fludara</other_name>
    <other_name>SH T 586</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Inotuzumab Ozogamicin</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (transplant)</arm_group_label>
    <other_name>Besponsa</other_name>
    <other_name>CMC-544</other_name>
    <other_name>Way 207294</other_name>
    <other_name>WAY-207294</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methotrexate</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (transplant)</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>Procedure</intervention_type>
    <intervention_name>Peripheral Blood Stem Cell Transplantation</intervention_name>
    <description>Undergo allogeneic PBSC transplant</description>
    <arm_group_label>Treatment (transplant)</arm_group_label>
    <other_name>PBPC transplantation</other_name>
    <other_name>PBSCT</other_name>
    <other_name>Peripheral Blood Progenitor Cell Transplantation</other_name>
    <other_name>Peripheral Stem Cell Support</other_name>
    <other_name>Peripheral Stem Cell Transplant</other_name>
    <other_name>Peripheral Stem Cell Transplantation</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Rituximab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (transplant)</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>RTXM83</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tacrolimus</intervention_name>
    <description>Given IV or PO</description>
    <arm_group_label>Treatment (transplant)</arm_group_label>
    <other_name>FK 506</other_name>
    <other_name>Fujimycin</other_name>
    <other_name>Hecoria</other_name>
    <other_name>Prograf</other_name>
    <other_name>Protopic</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with B-cell hematological malignancies who are eligible for allogeneic&#xD;
             transplantation&#xD;
&#xD;
          -  Patients must have a fully-matched sibling donor or a matched unrelated donor&#xD;
             identified&#xD;
&#xD;
          -  Performance score of at least 80% by Karnofsky or 0 to 2 Eastern Cooperative Oncology&#xD;
             Group (ECOG)&#xD;
&#xD;
          -  Left ventricular ejection fraction (EF) &gt;= 45% with no uncontrolled arrhythmias or&#xD;
             symptomatic heart disease&#xD;
&#xD;
          -  Forced expiratory volume in one second (FEV1) &gt;= 50%&#xD;
&#xD;
          -  Forced vital capacity (FVC) &gt;= 50%&#xD;
&#xD;
          -  Corrected diffusion capacity of the lung for carbon monoxide (DLCO) &gt;= 50%&#xD;
&#xD;
          -  Serum creatinine &lt; 1.6 mg/dL&#xD;
&#xD;
          -  Serum bilirubin &lt; 2 mg/dL upper limit of normal (unless due to Gilbert's disease;&#xD;
             patient with this disease should have a right upper quadrant ultrasound evaluation&#xD;
             before treatment)&#xD;
&#xD;
          -  Serum glutamate pyruvate transaminase (SGPT) &lt; 2 x upper limit of normal&#xD;
&#xD;
          -  Men and women of reproductive potential must agree to follow accepted birth control&#xD;
             methods (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with&#xD;
             spermicide, condom with spermicide, or abstinence) for the duration of the study&#xD;
&#xD;
          -  Negative beta human chorionic gonadotropin (HCG) test in a woman with child bearing&#xD;
             potential (defined as not post-menopausal for 12 months or no previous surgical&#xD;
             sterilization) or currently breast-feeding; pregnancy testing is not required for&#xD;
             post-menopausal or surgically sterilized women&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient with active central nervous system (CNS) involvement&#xD;
&#xD;
          -  Known infection with human immunodeficiency virus (HIV), human T-cell lymphotropic&#xD;
             virus (HTLV)-I, hepatitis B, or hepatitis C&#xD;
&#xD;
          -  Patients with other malignancies diagnosed within 2 years prior to study registration;&#xD;
             skin squamous or basal cell carcinoma are exceptions&#xD;
&#xD;
          -  Active bacterial, viral or fungal infections&#xD;
&#xD;
          -  History of stroke within 6 months&#xD;
&#xD;
          -  History of biliary colic attack&#xD;
&#xD;
          -  A prior autologous transplant within 3 months of study entry or allogeneic stem cell&#xD;
             transplant&#xD;
&#xD;
          -  Serious medical or psychiatric illness likely to interfere with participation in this&#xD;
             clinical study&#xD;
&#xD;
          -  Patient has received other investigational drugs within 3 weeks before study&#xD;
             registration&#xD;
&#xD;
          -  Serious nonmalignant disease which, in the opinion of the investigator would&#xD;
             compromise protocol objectives&#xD;
&#xD;
          -  Prior exposure to CMC-544 within past 6 months&#xD;
&#xD;
          -  Established refractoriness to CMC-544&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Issa Khouri</last_name>
    <role>Principal Investigator</role>
    <affiliation>M.D. Anderson Cancer Center</affiliation>
  </overall_official>
  <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>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mdanderson.org</url>
    <description>University of Texas MD Anderson Cancer Center Website</description>
  </link>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>August 10, 2012</study_first_submitted>
  <study_first_submitted_qc>August 10, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 14, 2012</study_first_posted>
  <last_update_submitted>July 20, 2023</last_update_submitted>
  <last_update_submitted_qc>July 20, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 21, 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>Hematologic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rituximab</mesh_term>
    <mesh_term>Antineoplastic Agents, Immunological</mesh_term>
    <mesh_term>Inotuzumab Ozogamicin</mesh_term>
    <mesh_term>Methotrexate</mesh_term>
    <mesh_term>Fludarabine</mesh_term>
    <mesh_term>Fludarabine phosphate</mesh_term>
    <mesh_term>Bendamustine Hydrochloride</mesh_term>
    <mesh_term>Antibodies</mesh_term>
    <mesh_term>Immunoglobulins</mesh_term>
    <mesh_term>Antibodies, Monoclonal</mesh_term>
    <mesh_term>Tacrolimus</mesh_term>
    <mesh_term>Thymoglobulin</mesh_term>
    <mesh_term>Antilymphocyte Serum</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/NCT01664910
org study id: 2012-0265
secondary id: NCI-2012-02072
secondary id: 2012-0265
nct id: NCT01664910
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 the best dose of inotuzumab ozogamicin
      when given together with fludarabine phosphate, bendamustine hydrochloride, and rituximab
      before donor stem cell transplant in treating patients with lymphoid malignancies. Giving
      chemotherapy drugs, such as fludarabine phosphate and bendamustine hydrochloride, before a
      donor peripheral blood stem cell transplant helps stop the growth of cancer cells or abnormal
      cell and helps stop the patient's immune system from rejecting the donor's stem cells.
      Immunotherapy with monoclonal antibodies, such as inotuzumab ozogamicin and rituximab, may
      help the body's immune system attack the cancer, and may interfere with the ability of tumor
      cells to grow and spread. When the healthy stem cells from a donor are infused into the
      patient they may help the patient's bone marrow make stem cells, red blood cells, white blood
      cells, and platelets. Sometimes the transplanted cell from a donor can make an immune system
      response against the body's normal cells. Giving fludarabine phosphate and bendamustine
      hydrochloride before the transplant together with anti-thymocyte globulin and tacrolimus may
      stop this from happening.
PRIMARY OBJECTIVES:

      I. To characterize the safety of anti-cluster of differentiation (CD) 22 immunoconjugate
      inotuzumab ozogamicin (CMC-544), when administered in conjunction with fludarabine
      (fludarabine phosphate), bendamustine (bendamustine hydrochloride), and rituximab as
      non-myeloablative preparative regimen for allogeneic stem cell transplantation for
      CD22-positive lymphoid malignancies.

      SECONDARY OBJECTIVES:

      I. To estimate tumor response. II. To determine overall and event-free survival rates by
      histology subtype.

      OUTLINE: This is a dose-escalation study of inotuzumab ozogamicin.

      Patients receive inotuzumab ozogamicin intravenously (IV) over 1 hour on day -13, and
      fludarabine phosphate IV over 1 hour and bendamustine hydrochloride IV over 30 minutes to 1
      hour on days -5 to -3. Patients with CD20-positive disease also receive rituximab IV over 4-6
      hours on days -6, 1, and 8 and patients with matched unrelated donors (MUD) receive
      anti-thymocyte globulin IV over 3-4 hours on days -2 to -1. All patients also receive
      tacrolimus IV over 24 hours continuously or orally (PO) daily beginning on days -2 to 180
      followed by taper in the absence of graft-versus-host disease (GVHD) and methotrexate IV over
      30 minutes on days 1, 3, and 6 (1, 3, 6, and 11 in patients with MUD). Patients undergo
      allogeneic bone marrow (BM) or peripheral blood stem cell (PBSC) transplant on day 0.

      After completion of study treatment, patients are followed up periodically.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum-tolerated dose (MTD) of inotuzumab ozogamicin
time frame: Up to 30 days
description: Defined as the highest dose for which the probability of toxicity is closest to 30%.
measure: Incidence of dose-limiting toxicity
time frame: Up to 30 days
description: Defined as grade III or IV renal, hepatic, intestinal, neurologic, pulmonary or cardiac adverse events, as well as graft failure or death at any time.
measure: Objective overall response (complete remission and partial remission)
time frame: Up to 3 years
description: Estimated with a 95% confidence interval in the dose that is declared the MTD. Logistic regression will be used to assess the association between response and disease and clinical characteristics of interest.
measure: Overall survival (OS)
time frame: Up to 3 years
description: Kaplan-Meier survival curves will be used to estimate OS. Cox proportional hazards regression methodology will be used to assess the association between disease and clinical characteristics and the survival outcomes.
measure: Recurrence-free survival
time frame: Up to 3 years
description: Kaplan-Meier survival curves will be used to estimate recurrence-free survival. Cox proportional hazards regression methodology will be used to assess the association between disease and clinical characteristics and the survival outcomes.
measure: Cumulative incidence of acute and chronic graft versus host disease (GVHD)
time frame: Up to 3 years
description: The method of Gooley et al will be used to estimate the cumulative incidence of acute and chronic GVHD.
arm group label: Treatment (transplant)
arm group type: Experimental
description: Patients receive inotuzumab ozogamicin IV over 1 hour on day -13, and fludarabine phosphate IV over 1 hour and bendamustine hydrochloride IV over 30 minutes to 1 hour on days -5 to -3. Patients with CD20-positive disease also receive rituximab IV over 4-6 hours on days -6, 1, and 8 and patients with MUD receive anti-thymocyte globulin IV over 3-4 hours on days -2 to -1. All patients also receive tacrolimus IV over 24 hours continuously or PO daily beginning on days -2 to 180 followed by taper in the absence of GVHD and methotrexate IV over 30 minutes on days 1, 3, and 6 (1, 3, 6, and 11 in patients with MUD). Patients undergo allogeneic BM or PBSC transplant on day 0.
intervention type: Procedure
intervention name: Allogeneic Bone Marrow Transplantation
description: Undergo allogeneic BM transplant
arm group label: Treatment (transplant)
other name: Allo BMT
other name: Allogeneic BMT
intervention type: Procedure
intervention name: Allogeneic Hematopoietic Stem Cell Transplantation
description: Undergo allogeneic PBSC or BM transplant
arm group label: Treatment (transplant)
other name: Allogeneic Hematopoietic Cell Transplantation
other name: Allogeneic Stem Cell Transplantation
other name: HSC
other name: HSCT
intervention type: Biological
intervention name: Anti-Thymocyte Globulin
description: Given IV
arm group label: Treatment (transplant)
other name: Antithymocyte Globulin
other name: Antithymocyte Serum
other name: ATG
other name: ATGAM
other name: ATS
other name: Thymoglobulin
intervention type: Drug
intervention name: Bendamustine Hydrochloride
description: Given IV
arm group label: Treatment (transplant)
other name: Bendamustin Hydrochloride
other name: Cytostasan Hydrochloride
other name: Levact
other name: Ribomustin
other name: SyB L-0501
other name: Treanda
intervention type: Drug
intervention name: Fludarabine Phosphate
description: Given IV
arm group label: Treatment (transplant)
other name: 2-F-ara-AMP
other name: 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
other name: Beneflur
other name: Fludara
other name: SH T 586
intervention type: Biological
intervention name: Inotuzumab Ozogamicin
description: Given IV
arm group label: Treatment (transplant)
other name: Besponsa
other name: CMC-544
other name: Way 207294
other name: WAY-207294
intervention type: Drug
intervention name: Methotrexate
description: Given IV
arm group label: Treatment (transplant)
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: Procedure
intervention name: Peripheral Blood Stem Cell Transplantation
description: Undergo allogeneic PBSC transplant
arm group label: Treatment (transplant)
other name: PBPC transplantation
other name: PBSCT
other name: Peripheral Blood Progenitor Cell Transplantation
other name: Peripheral Stem Cell Support
other name: Peripheral Stem Cell Transplant
other name: Peripheral Stem Cell Transplantation
intervention type: Biological
intervention name: Rituximab
description: Given IV
arm group label: Treatment (transplant)
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: RTXM83
intervention type: Drug
intervention name: Tacrolimus
description: Given IV or PO
arm group label: Treatment (transplant)
other name: FK 506
other name: Fujimycin
other name: Hecoria
other name: Prograf
other name: Protopic
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Issa Khouri
role: Principal Investigator
affiliation: M.D. Anderson Cancer Center
facility: 
country: United States
url: http://www.mdanderson.org
description: University of Texas MD Anderson Cancer Center Website
responsible party type: Sponsor
mesh term: Hematologic Neoplasms
mesh term: Rituximab
mesh term: Antineoplastic Agents, Immunological
mesh term: Inotuzumab Ozogamicin
mesh term: Methotrexate
mesh term: Fludarabine
mesh term: Fludarabine phosphate
mesh term: Bendamustine Hydrochloride
mesh term: Antibodies
mesh term: Immunoglobulins
mesh term: Antibodies, Monoclonal
mesh term: Tacrolimus
mesh term: Thymoglobulin
mesh term: Antilymphocyte Serum