<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/NCT01701986</url>
  </required_header>
  <id_info>
    <org_study_id>2012-0506</org_study_id>
    <secondary_id>NCI-2012-02055</secondary_id>
    <secondary_id>2012-0506</secondary_id>
    <secondary_id>P30CA016672</secondary_id>
    <nct_id>NCT01701986</nct_id>
  </id_info>
  <brief_title>Gemcitabine Hydrochloride, Clofarabine, and Busulfan Before Donor Stem Cell Transplant in Treating Patients With Refractory B-Cell or T-Cell Non-Hodgkin Lymphoma or Hodgkin Lymphoma</brief_title>
  <official_title>Gemcitabine/Clofarabine/Busulfan and Allogeneic Transplantation for Aggressive Lymphomas</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 gemcitabine hydrochloride,&#xD;
      clofarabine, and busulfan before donor stem cell transplant and to see how well it works in&#xD;
      treating patients with B-cell or T-cell non-Hodgkin lymphoma or Hodgkin lymphoma that does&#xD;
      not respond to treatment. Giving chemotherapy before a donor bone marrow or peripheral blood&#xD;
      stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's&#xD;
      immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor&#xD;
      are infused into the patient they may help the patient's bone marrow make stem cells, red&#xD;
      blood cells, white blood cells, and platelets.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To define the maximum tolerated dose (MTD) of infusional gemcitabine (gemcitabine&#xD;
      hydrochloride) combined with fixed doses of clofarabine and busulfan in patients with&#xD;
      lymphoma receiving an allogeneic stem-cell transplant (alloSCT).&#xD;
&#xD;
      II. To estimate the day +100 success rate, defined as percentage of patients who are alive,&#xD;
      engrafted and without grade 3-4 graft-versus (vs.)-host-disease (GVHD).&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To estimate the day +100 success rate (defined as percentage of patients who are alive,&#xD;
      engrafted and without grade 3-4 graft-vs.-host-disease [GVHD]).&#xD;
&#xD;
      II. To estimate the rate of event-free (EFS). III. To estimate the rate of overall survival&#xD;
      (OS). IV. To estimate the response rate (RR) (defined as # of responses / # of patients with&#xD;
      measurable tumors).&#xD;
&#xD;
      V. To estimate the complete response (CR) rate (defined as # of complete responses / # of&#xD;
      patients with measurable tumors).&#xD;
&#xD;
      VI. To estimate the incidence of grade 2-4 and grade 3-4 acute GVHD. VII. To estimate the&#xD;
      incidence of limited and extensive chronic GVHD.&#xD;
&#xD;
      OUTLINE: This is a phase I, dose-escalation study of gemcitabine hydrochloride followed by a&#xD;
      phase II study.&#xD;
&#xD;
      PREPARATIVE REGIMEN: Patients receive gemcitabine hydrochloride intravenously (IV) over&#xD;
      40-180 minutes on days -6 and -4, clofarabine IV over 1 hour on days -6 to -3, and busulfan&#xD;
      IV over 3 hours on days -6 to -3. Patients with matched unrelated donors also receive&#xD;
      antithymocyte globulin IV on days -3 to -1 and patients with cluster of differentiation&#xD;
      (CD)20-positive disease also receive rituximab IV on days -14, -7, 1, and 8.&#xD;
&#xD;
      TRANSPLANT: Patients undergo allogeneic bone marrow (BMT) or peripheral blood stem cell&#xD;
      transplant (PBSCT) on day 0.&#xD;
&#xD;
      GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously over 24 hours or orally (PO).&#xD;
      Beginning on day 0, patients receive mycophenolate mofetil IV over 2 hours or PO thrice daily&#xD;
      (TID).&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 3, 6, and 12 months, and&#xD;
      then every 6 months for 4 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">October 25, 2012</start_date>
  <completion_date type="Anticipated">May 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">May 31, 2024</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>Optimal dose of gemcitabine hydrochloride determined by dose limiting toxicity (Phase I)</measure>
    <time_frame>Within 30 days of transplant</time_frame>
    <description>Defined as grade 3-4 mucositis lasting for more than 3 days at peak severity or grade 3-4 skin toxicity lasting for more than 3 days at peak severity. The Bayesian Time to Event Continual Reassessment Method will be applied to determine the optimal gemcitabine dose in phase I.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Success rate (Phase II)</measure>
    <time_frame>Up to 100 days post-transplant</time_frame>
    <description>Defined as percentage of patients who are alive, engrafted and without grade 3-4 graft versus host disease (GVHD).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Rate of event-free survival (Phase II)</measure>
    <time_frame>Up to 5 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Overall survival (Phase II)</measure>
    <time_frame>Up to 5 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Response rate (Phase II)</measure>
    <time_frame>Up to 5 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Complete response rate (Phase II)</measure>
    <time_frame>Up to 5 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of grade 2-4 and grade 3-4 acute GVHD (Phase II)</measure>
    <time_frame>Up to 5 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of limited and extensive chronic GVHD (Phase II)</measure>
    <time_frame>Up to 5 years</time_frame>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Hematopoietic Cell Transplantation Recipient</condition>
  <condition>Refractory B-Cell Non-Hodgkin Lymphoma</condition>
  <condition>Refractory Hodgkin Lymphoma</condition>
  <condition>Refractory T-Cell Non-Hodgkin Lymphoma</condition>
  <arm_group>
    <arm_group_label>Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>PREPARATIVE REGIMEN: Patients receive gemcitabine hydrochloride IV over 40-180 minutes on days -6 and -4, clofarabine IV over 1 hour on days -6 to -3, and busulfan IV over 3 hours on days -6 to -3. Patients with matched unrelated donors also receive antithymocyte globulin IV on days -3 to -1 and patients with CD20-positive disease also receive rituximab IV on days -14, -7, 1, and 8.&#xD;
TRANSPLANT: Patients undergo allogeneic BMT or PBSCT on day 0.&#xD;
GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously over 24 hours or PO beginning on day -2 for up to 6 months and mycophenolate mofetil IV over 2 hours or PO TID beginning day 0.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Allogeneic Bone Marrow Transplantation</intervention_name>
    <description>Undergo allogeneic BMT</description>
    <arm_group_label>Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)</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 BMT or PBSCT</description>
    <arm_group_label>Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)</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 (gemcitabine, clofarabine, busulfan, BMT or PBSCT)</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>Busulfan</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)</arm_group_label>
    <other_name>1, 4-Bis[methanesulfonoxy]butane</other_name>
    <other_name>BUS</other_name>
    <other_name>Bussulfam</other_name>
    <other_name>Busulfanum</other_name>
    <other_name>Busulfex</other_name>
    <other_name>Busulphan</other_name>
    <other_name>CB 2041</other_name>
    <other_name>CB-2041</other_name>
    <other_name>Glyzophrol</other_name>
    <other_name>GT 41</other_name>
    <other_name>GT-41</other_name>
    <other_name>Joacamine</other_name>
    <other_name>Methanesulfonic Acid Tetramethylene Ester</other_name>
    <other_name>Methanesulfonic acid, tetramethylene ester</other_name>
    <other_name>Mielucin</other_name>
    <other_name>Misulban</other_name>
    <other_name>Misulfan</other_name>
    <other_name>Mitosan</other_name>
    <other_name>Myeleukon</other_name>
    <other_name>Myeloleukon</other_name>
    <other_name>Myelosan</other_name>
    <other_name>Mylecytan</other_name>
    <other_name>Myleran</other_name>
    <other_name>Sulfabutin</other_name>
    <other_name>Tetramethylene Bis(methanesulfonate)</other_name>
    <other_name>Tetramethylene bis[methanesulfonate]</other_name>
    <other_name>WR-19508</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Clofarabine</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)</arm_group_label>
    <other_name>Clofarex</other_name>
    <other_name>Clolar</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gemcitabine Hydrochloride</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)</arm_group_label>
    <other_name>dFdCyd</other_name>
    <other_name>Difluorodeoxycytidine Hydrochloride</other_name>
    <other_name>Gemzar</other_name>
    <other_name>LY-188011</other_name>
    <other_name>LY188011</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mycophenolate Mofetil</intervention_name>
    <description>Given IV then PO</description>
    <arm_group_label>Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)</arm_group_label>
    <other_name>Cellcept</other_name>
    <other_name>MMF</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Peripheral Blood Stem Cell Transplantation</intervention_name>
    <description>Undergo allogeneic PBSCT</description>
    <arm_group_label>Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)</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>Other</intervention_type>
    <intervention_name>Pharmacological Study</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Rituximab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)</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 then PO</description>
    <arm_group_label>Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)</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 refractory B-cell or T-cell non-Hodgkin's lymphoma or Hodgkin's lymphoma&#xD;
             who are eligible for allogeneic transplantation&#xD;
&#xD;
          -  An 8/8 human leukocyte antigen (HLA) matched (high resolution typing at A, B, C, DRB1)&#xD;
             sibling or unrelated donor&#xD;
&#xD;
          -  Left ventricular ejection fraction (EF) &gt;= 45%&#xD;
&#xD;
          -  Forced expiratory volume in one second (FEV1) &gt;= 50%&#xD;
&#xD;
          -  Forced vital capacity (FVC) &gt;= 50%&#xD;
&#xD;
          -  Diffusing capacity of the lung for carbon monoxide (DLCO) &gt;= 50%&#xD;
&#xD;
          -  Estimated serum creatinine clearance &gt;= 50 ml/min (using the Cockcroft-Gault formula)&#xD;
&#xD;
          -  Serum creatinine =&lt; 1.6 mg/dL&#xD;
&#xD;
          -  Serum bilirubin =&lt; 2 x upper limit of normal&#xD;
&#xD;
          -  Serum glutamate pyruvate transaminase (SGPT) =&lt; 2 x upper limit of normal&#xD;
&#xD;
          -  Voluntary signed Institutional Review Board (IRB)-approved informed consent before&#xD;
             performance of any study-related procedure not part of normal medical care, with the&#xD;
             understanding that consent may be withdrawn by the subject at any time without&#xD;
             prejudice to future medical care&#xD;
&#xD;
          -  Men and women of reproductive potential must agree to follow accepted birth control&#xD;
             methods for the duration of the study; female subject is either post-menopausal or&#xD;
             surgically sterilized or willing to use an acceptable method of birth control (i.e., a&#xD;
             hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with&#xD;
             spermicide, or abstinence) for the duration of the study; male subject agrees to use&#xD;
             an acceptable method for contraception for the duration of the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient with active central nervous system (CNS) disease&#xD;
&#xD;
          -  Pregnancy (positive beta human chorionic gonadotropin [HCG] test in a woman with child&#xD;
             bearing 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;
          -  Active hepatitis B, either active carrier (hepatitis B virus surface antigen [HBsAg]&#xD;
             +) or viremic (hepatitis B virus [HBV] deoxyribonucleic acid [DNA] &gt;= 10,000&#xD;
             copies/mL, or &gt;= 2,000 IU/mL)&#xD;
&#xD;
          -  Evidence of either cirrhosis or stage 3-4 liver fibrosis in patients with chronic&#xD;
             hepatitis C or positive hepatitis C serology&#xD;
&#xD;
          -  Human immunodeficiency virus (HIV) infection&#xD;
&#xD;
          -  Active uncontrolled bacterial, viral or fungal infections&#xD;
&#xD;
          -  Exposure to other investigational drugs within 2 weeks before enrollment&#xD;
&#xD;
          -  Grade &gt;= 3 non-hematologic toxicity from previous therapy that has not resolved to =&lt;&#xD;
             grade 1&#xD;
&#xD;
          -  Radiation therapy to head and neck (excluding eyes), and internal organs of chest,&#xD;
             abdomen or pelvis in the month prior to enrollment&#xD;
&#xD;
          -  Prior whole brain irradiation&#xD;
&#xD;
          -  Prior autologous stem-cell transplant (SCT) in the prior 3 months&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yago L Nieto, MD,PHD</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>August 2023</verification_date>
  <study_first_submitted>October 3, 2012</study_first_submitted>
  <study_first_submitted_qc>October 4, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 5, 2012</study_first_posted>
  <last_update_submitted>August 9, 2023</last_update_submitted>
  <last_update_submitted_qc>August 9, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 14, 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>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, Non-Hodgkin</mesh_term>
    <mesh_term>Hodgkin Disease</mesh_term>
    <mesh_term>Lymphoma, B-Cell</mesh_term>
    <mesh_term>Lymphoma, T-Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mycophenolic Acid</mesh_term>
    <mesh_term>Rituximab</mesh_term>
    <mesh_term>Antineoplastic Agents, Immunological</mesh_term>
    <mesh_term>Gemcitabine</mesh_term>
    <mesh_term>Busulfan</mesh_term>
    <mesh_term>Clofarabine</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/NCT01701986
org study id: 2012-0506
secondary id: NCI-2012-02055
secondary id: 2012-0506
secondary id: P30CA016672
nct id: NCT01701986
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 gemcitabine hydrochloride,
      clofarabine, and busulfan before donor stem cell transplant and to see how well it works in
      treating patients with B-cell or T-cell non-Hodgkin lymphoma or Hodgkin lymphoma that does
      not respond to treatment. Giving chemotherapy before a donor bone marrow or peripheral blood
      stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's
      immune system from rejecting the donor's stem cells. 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.
PRIMARY OBJECTIVES:

      I. To define the maximum tolerated dose (MTD) of infusional gemcitabine (gemcitabine
      hydrochloride) combined with fixed doses of clofarabine and busulfan in patients with
      lymphoma receiving an allogeneic stem-cell transplant (alloSCT).

      II. To estimate the day +100 success rate, defined as percentage of patients who are alive,
      engrafted and without grade 3-4 graft-versus (vs.)-host-disease (GVHD).

      SECONDARY OBJECTIVES:

      I. To estimate the day +100 success rate (defined as percentage of patients who are alive,
      engrafted and without grade 3-4 graft-vs.-host-disease [GVHD]).

      II. To estimate the rate of event-free (EFS). III. To estimate the rate of overall survival
      (OS). IV. To estimate the response rate (RR) (defined as # of responses / # of patients with
      measurable tumors).

      V. To estimate the complete response (CR) rate (defined as # of complete responses / # of
      patients with measurable tumors).

      VI. To estimate the incidence of grade 2-4 and grade 3-4 acute GVHD. VII. To estimate the
      incidence of limited and extensive chronic GVHD.

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

      PREPARATIVE REGIMEN: Patients receive gemcitabine hydrochloride intravenously (IV) over
      40-180 minutes on days -6 and -4, clofarabine IV over 1 hour on days -6 to -3, and busulfan
      IV over 3 hours on days -6 to -3. Patients with matched unrelated donors also receive
      antithymocyte globulin IV on days -3 to -1 and patients with cluster of differentiation
      (CD)20-positive disease also receive rituximab IV on days -14, -7, 1, and 8.

      TRANSPLANT: Patients undergo allogeneic bone marrow (BMT) or peripheral blood stem cell
      transplant (PBSCT) on day 0.

      GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously over 24 hours or orally (PO).
      Beginning on day 0, patients receive mycophenolate mofetil IV over 2 hours or PO thrice daily
      (TID).

      After completion of study treatment, patients are followed up at 3, 6, and 12 months, and
      then every 6 months for 4 years.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Optimal dose of gemcitabine hydrochloride determined by dose limiting toxicity (Phase I)
time frame: Within 30 days of transplant
description: Defined as grade 3-4 mucositis lasting for more than 3 days at peak severity or grade 3-4 skin toxicity lasting for more than 3 days at peak severity. The Bayesian Time to Event Continual Reassessment Method will be applied to determine the optimal gemcitabine dose in phase I.
measure: Success rate (Phase II)
time frame: Up to 100 days post-transplant
description: Defined as percentage of patients who are alive, engrafted and without grade 3-4 graft versus host disease (GVHD).
measure: Rate of event-free survival (Phase II)
time frame: Up to 5 years
measure: Overall survival (Phase II)
time frame: Up to 5 years
measure: Response rate (Phase II)
time frame: Up to 5 years
measure: Complete response rate (Phase II)
time frame: Up to 5 years
measure: Incidence of grade 2-4 and grade 3-4 acute GVHD (Phase II)
time frame: Up to 5 years
measure: Incidence of limited and extensive chronic GVHD (Phase II)
time frame: Up to 5 years
arm group label: Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)
arm group type: Experimental
description: PREPARATIVE REGIMEN: Patients receive gemcitabine hydrochloride IV over 40-180 minutes on days -6 and -4, clofarabine IV over 1 hour on days -6 to -3, and busulfan IV over 3 hours on days -6 to -3. Patients with matched unrelated donors also receive antithymocyte globulin IV on days -3 to -1 and patients with CD20-positive disease also receive rituximab IV on days -14, -7, 1, and 8.
TRANSPLANT: Patients undergo allogeneic BMT or PBSCT on day 0.
GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously over 24 hours or PO beginning on day -2 for up to 6 months and mycophenolate mofetil IV over 2 hours or PO TID beginning day 0.
intervention type: Procedure
intervention name: Allogeneic Bone Marrow Transplantation
description: Undergo allogeneic BMT
arm group label: Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)
other name: Allo BMT
other name: Allogeneic BMT
intervention type: Procedure
intervention name: Allogeneic Hematopoietic Stem Cell Transplantation
description: Undergo allogeneic BMT or PBSCT
arm group label: Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)
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 (gemcitabine, clofarabine, busulfan, BMT or PBSCT)
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: Busulfan
description: Given IV
arm group label: Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)
other name: 1, 4-Bis[methanesulfonoxy]butane
other name: BUS
other name: Bussulfam
other name: Busulfanum
other name: Busulfex
other name: Busulphan
other name: CB 2041
other name: CB-2041
other name: Glyzophrol
other name: GT 41
other name: GT-41
other name: Joacamine
other name: Methanesulfonic Acid Tetramethylene Ester
other name: Methanesulfonic acid, tetramethylene ester
other name: Mielucin
other name: Misulban
other name: Misulfan
other name: Mitosan
other name: Myeleukon
other name: Myeloleukon
other name: Myelosan
other name: Mylecytan
other name: Myleran
other name: Sulfabutin
other name: Tetramethylene Bis(methanesulfonate)
other name: Tetramethylene bis[methanesulfonate]
other name: WR-19508
intervention type: Drug
intervention name: Clofarabine
description: Given IV
arm group label: Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)
other name: Clofarex
other name: Clolar
intervention type: Drug
intervention name: Gemcitabine Hydrochloride
description: Given IV
arm group label: Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)
other name: dFdCyd
other name: Difluorodeoxycytidine Hydrochloride
other name: Gemzar
other name: LY-188011
other name: LY188011
intervention type: Drug
intervention name: Mycophenolate Mofetil
description: Given IV then PO
arm group label: Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)
other name: Cellcept
other name: MMF
intervention type: Procedure
intervention name: Peripheral Blood Stem Cell Transplantation
description: Undergo allogeneic PBSCT
arm group label: Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)
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: Other
intervention name: Pharmacological Study
description: Correlative studies
arm group label: Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)
intervention type: Biological
intervention name: Rituximab
description: Given IV
arm group label: Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)
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 then PO
arm group label: Treatment (gemcitabine, clofarabine, busulfan, BMT or PBSCT)
other name: FK 506
other name: Fujimycin
other name: Hecoria
other name: Prograf
other name: Protopic
criteria: 
gender: All
minimum age: 12 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Yago L Nieto, MD,PHD
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: Lymphoma
mesh term: Lymphoma, Non-Hodgkin
mesh term: Hodgkin Disease
mesh term: Lymphoma, B-Cell
mesh term: Lymphoma, T-Cell
mesh term: Mycophenolic Acid
mesh term: Rituximab
mesh term: Antineoplastic Agents, Immunological
mesh term: Gemcitabine
mesh term: Busulfan
mesh term: Clofarabine
mesh term: Antibodies
mesh term: Immunoglobulins
mesh term: Antibodies, Monoclonal
mesh term: Tacrolimus
mesh term: Thymoglobulin
mesh term: Antilymphocyte Serum