<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/NCT02250937</url>
  </required_header>
  <id_info>
    <org_study_id>2014-0431</org_study_id>
    <secondary_id>NCI-2014-02324</secondary_id>
    <secondary_id>2014-0431</secondary_id>
    <nct_id>NCT02250937</nct_id>
  </id_info>
  <brief_title>Venetoclax and Sequential Busulfan, Cladribine, and Fludarabine Phosphate Before Donor Stem Cell Transplant in Treating Patients With Acute Myelogenous Leukemia or Myelodysplastic Syndrome</brief_title>
  <official_title>Allogeneic Transplantation Using Venetoclax, Timed Sequential Busulfan,Cladribine, and Fludarabine Conditioning in Patients With AML and MDS</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>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This randomized phase II trial studies how well venetoclax and sequential busulfan,&#xD;
      cladribine, and fludarabine phosphate before donor stem cell transplant work in treating&#xD;
      patients with acute myelogenous leukemia or myelodysplastic syndrome. Giving chemotherapy&#xD;
      before a donor peripheral blood stem cell transplant helps kill cancer cells in the body and&#xD;
      helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to&#xD;
      grow. When the healthy stem cells from a donor are infused into a patient, they may help the&#xD;
      patient's bone marrow make more healthy cells and platelets and may help destroy any&#xD;
      remaining cancer cells.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      I. To compare progression free survival of two schedules of venetoclax, timed sequential&#xD;
      busulfan, cladribine and fludarabine conditioning regimen in patients with acute myelogenous&#xD;
      leukemia (AML) and myelodysplastic syndrome (MDS).&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. Compare overall survival between the two schedules. II. Compare non relapse mortality&#xD;
      between the two schedules. III. Compare neutrophil and platelet engraftment between the two&#xD;
      schedules. IV. Compare acute and chronic graft-versus-host disease (GVHD) between the two&#xD;
      schedules.&#xD;
&#xD;
      V. Compare cumulative incidence of relapse between the two schedules. VI. Compare grade&#xD;
      III/IV toxicity between the two schedules.&#xD;
&#xD;
      TERTIARY OBJECTIVES:&#xD;
&#xD;
      I. To study chemotherapy resistance. II. To study deoxyribonucleic acid (DNA) damage. III. To&#xD;
      study immune recovery and cytokines (both in plasma and cells). IV. To study BCL-2 family&#xD;
      expression, stem cell surface markers and intracellular signaling markers in AML cells at the&#xD;
      time of relapse.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      PREPARATIVE REGIMEN: Patients are randomized to 1 of 2 treatment arms.&#xD;
&#xD;
      ARM I: Patients receive venetoclax orally (PO) once daily (QD) on days -22 to -3 and busulfan&#xD;
      intravenously (IV) over 3 hours on days -13 and -12. Patients then receive fludarabine&#xD;
      phosphate IV over 1 hour, cladribine IV over 2 hours, and busulfan IV over 3 hours on days -6&#xD;
      to -3.&#xD;
&#xD;
      ARM II: Patients receive venetoclax PO QD on days -22 to -3 and busulfan IV over 3 hours on&#xD;
      days -20 and -13. Patients then receive fludarabine phosphate IV over 1 hour, cladribine IV&#xD;
      over 2 hours, and busulfan IV over 3 hours on days -6 to -3.&#xD;
&#xD;
      TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant (PBSCT) on day&#xD;
      0.&#xD;
&#xD;
      After completion of study treatment, patients are followed up for 2.5 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">October 27, 2014</start_date>
  <completion_date type="Anticipated">October 31, 2025</completion_date>
  <primary_completion_date type="Anticipated">October 31, 2025</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>At 6 months</time_frame>
    <description>The method of Kaplan and Meier will be used to estimate distribution of progression free survival.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Disease free survival (DFS)</measure>
    <time_frame>Up to 2.5 years</time_frame>
    <description>Will test whether there is strong evidence that DFS differs between the two arms using a stratified log-rank test. Will use the Lan-DeMets alpha spending approach with an O'Brien-Fleming stopping boundary to compare the two arms.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of toxicity of these regimens</measure>
    <time_frame>Up to 2.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative incidence of acute graft versus host disease (GVHD)</measure>
    <time_frame>Up to 2.5 years</time_frame>
    <description>Will use the method of Gooley et al to estimate the cumulative incidence of acute GVHD. Will use the method of Fine and Gary to fit regression models to the cumulative incidence outcomes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative incidence of chronic GVHD</measure>
    <time_frame>Up to 2.5 years</time_frame>
    <description>Will use the method of Gooley et al to estimate the cumulative incidence of chronic GVHD. Will use the method of Fine and Gary to fit regression models to the cumulative incidence outcomes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Up to 2.5 years</time_frame>
    <description>The method of Kaplan and Meier will be used to estimate the distribution of overall survival. Cox proportional hazards regression analysis will be used to model the association between overall survival and covariates of interest.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to neutrophil engraftment</measure>
    <time_frame>Up to 2.5 years</time_frame>
    <description>The method of Kaplan and Meier will be used to estimate time to neutrophil engraftment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to platelet engraftment</measure>
    <time_frame>Up to 2.5 years</time_frame>
    <description>The method of Kaplan and Meier will be used to estimate time to platelet engraftment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative incidence of relapse</measure>
    <time_frame>Up to 2.5 years</time_frame>
    <description>Will use the method of Gooley et al to estimate the cumulative incidence of relapse. Will use the method of Fine and Gary to fit regression models to the cumulative incidence outcomes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Non-relapse mortality</measure>
    <time_frame>Up to 2.5 years</time_frame>
    <description>Will use the method of Gooley et al to estimate the cumulative incidence of non-relapse mortality. Will use the method of Fine and Gary to fit regression models to the cumulative incidence outcomes. Logistic regression will be used to model the association between 100-day NRM and clinical and demographic covariates of interest.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">116</enrollment>
  <condition>Acute Myeloid Leukemia</condition>
  <condition>Myelodysplastic Syndrome</condition>
  <arm_group>
    <arm_group_label>Arm I (busulfan days -13 and -12 before PBSCT)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>PREPARATIVE REGIMEN: Patients receive venetoclax PO QD on days -22 to -3 and busulfan IV over 3 hours on days -13 and -12. Patients then receive fludarabine phosphate IV over 1 hour, cladribine IV over 2 hours, and busulfan IV over 3 hours on days -6 to -3.&#xD;
TRANSPLANT: Patients undergo allogeneic PBSCT on day 0.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm II (busulfan days -20 and -13 before PBSCT)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>PREPARATIVE REGIMEN: Patients receive venetoclax PO QD on days -22 to -3 and busulfan IV over 3 hours on days -20 and -13. Patients then receive fludarabine phosphate IV over 1 hour, cladribine IV over 2 hours, and busulfan IV over 3 hours on days -6 to -3.&#xD;
TRANSPLANT: Patients undergo allogeneic PBSCT on day 0.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Allogeneic Hematopoietic Stem Cell Transplantation</intervention_name>
    <description>Undergo allogeneic PBSCT</description>
    <arm_group_label>Arm I (busulfan days -13 and -12 before PBSCT)</arm_group_label>
    <arm_group_label>Arm II (busulfan days -20 and -13 before PBSCT)</arm_group_label>
    <other_name>Allogeneic</other_name>
    <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>
    <other_name>Stem Cell Transplantation, Allogeneic</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Busulfan</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (busulfan days -13 and -12 before PBSCT)</arm_group_label>
    <arm_group_label>Arm II (busulfan days -20 and -13 before 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>Cladribine</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (busulfan days -13 and -12 before PBSCT)</arm_group_label>
    <arm_group_label>Arm II (busulfan days -20 and -13 before PBSCT)</arm_group_label>
    <other_name>2-CdA</other_name>
    <other_name>2CDA</other_name>
    <other_name>CdA</other_name>
    <other_name>Cladribina</other_name>
    <other_name>Leustat</other_name>
    <other_name>Leustatin</other_name>
    <other_name>Leustatine</other_name>
    <other_name>RWJ-26251</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fludarabine Phosphate</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (busulfan days -13 and -12 before PBSCT)</arm_group_label>
    <arm_group_label>Arm II (busulfan days -20 and -13 before PBSCT)</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>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Arm I (busulfan days -13 and -12 before PBSCT)</arm_group_label>
    <arm_group_label>Arm II (busulfan days -20 and -13 before PBSCT)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Peripheral Blood Stem Cell Transplantation</intervention_name>
    <description>Undergo allogeneic PBSCT</description>
    <arm_group_label>Arm I (busulfan days -13 and -12 before PBSCT)</arm_group_label>
    <arm_group_label>Arm II (busulfan days -20 and -13 before 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>Arm I (busulfan days -13 and -12 before PBSCT)</arm_group_label>
    <arm_group_label>Arm II (busulfan days -20 and -13 before PBSCT)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Venetoclax</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Arm I (busulfan days -13 and -12 before PBSCT)</arm_group_label>
    <arm_group_label>Arm II (busulfan days -20 and -13 before PBSCT)</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>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with biopsy-proven acute myeloid leukemia or myelodysplastic syndrome with&#xD;
             persistent disease or in remission&#xD;
&#xD;
          -  Human leukocyte antigen (HLA)-identical sibling or 8/8 matched unrelated donor&#xD;
             transplant&#xD;
&#xD;
          -  Patients age 18 to 70 years old; eligibility for pediatric patients will be determined&#xD;
             in conjunction with an MD Anderson Cancer Center (MDACC) pediatrician; patients age&#xD;
             2-17 years may be enrolled after at least 10 adults (ages 18-70 years old) have been&#xD;
             assessed for safety at day 30&#xD;
&#xD;
          -  Direct bilirubin &lt; 1 mg/dl&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) &lt; 3 times upper limit of normal&#xD;
&#xD;
          -  Creatinine clearance &gt; 50 ml/min (calculated creatinine clearance is permitted)&#xD;
&#xD;
          -  Forced expiratory volume in 1 second (FEV1) &gt;= 50% of expected corrected for&#xD;
             hemoglobin and/or volume&#xD;
&#xD;
          -  Forced vital capacity (FVC) &gt;= 50% of expected corrected for hemoglobin and/or volume&#xD;
&#xD;
          -  Diffusing capacity of the lungs for carbon monoxide (DLCO) &gt;= 50% of expected&#xD;
             corrected for hemoglobin and/or volume&#xD;
&#xD;
          -  Children unable to perform pulmonary function tests (e.g., less than 7 years old)&#xD;
             pulse oximetry of &gt;= 92% on room air&#xD;
&#xD;
          -  Left ventricular ejection fraction (LVEF) &gt;= 40%&#xD;
&#xD;
          -  Patient, legally authorized representative (LAR), or parent able to sign informed&#xD;
             consent; able to give assent for patients age 7-17&#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; women of child bearing potential must be willing to use an effective&#xD;
             contraceptive measure while on study&#xD;
&#xD;
          -  Performance score of &gt;= 70 by Karnofsky/Lansky or performance status (PS) 0 or 1&#xD;
             (Eastern Cooperative Oncology Group [ECOG] =&lt; 1)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior allogeneic or autologous transplantation&#xD;
&#xD;
          -  Uncontrolled infections&#xD;
&#xD;
          -  Human immunodeficiency virus (HIV) seropositivity&#xD;
&#xD;
          -  Hematopoietic cell transplantation (HCT) co-morbidity index score &gt; 3; the principal&#xD;
             investigator is the final arbiter of eligibility for comorbidity score &gt; 3&#xD;
&#xD;
          -  Patients with prior coronary artery disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Uday R Popat</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>MD Anderson Cancer Center</description>
  </link>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>September 24, 2014</study_first_submitted>
  <study_first_submitted_qc>September 24, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 26, 2014</study_first_posted>
  <last_update_submitted>September 11, 2023</last_update_submitted>
  <last_update_submitted_qc>September 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 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>Preleukemia</mesh_term>
    <mesh_term>Myelodysplastic Syndromes</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fludarabine</mesh_term>
    <mesh_term>Fludarabine phosphate</mesh_term>
    <mesh_term>Busulfan</mesh_term>
    <mesh_term>Venetoclax</mesh_term>
    <mesh_term>Cladribine</mesh_term>
    <mesh_term>2-chloro-3'-deoxyadenosine</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/NCT02250937
org study id: 2014-0431
secondary id: NCI-2014-02324
secondary id: 2014-0431
nct id: NCT02250937
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This randomized phase II trial studies how well venetoclax and sequential busulfan,
      cladribine, and fludarabine phosphate before donor stem cell transplant work in treating
      patients with acute myelogenous leukemia or myelodysplastic syndrome. Giving chemotherapy
      before a donor peripheral blood stem cell transplant helps kill cancer cells in the body and
      helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to
      grow. When the healthy stem cells from a donor are infused into a patient, they may help the
      patient's bone marrow make more healthy cells and platelets and may help destroy any
      remaining cancer cells.
PRIMARY OBJECTIVE:

      I. To compare progression free survival of two schedules of venetoclax, timed sequential
      busulfan, cladribine and fludarabine conditioning regimen in patients with acute myelogenous
      leukemia (AML) and myelodysplastic syndrome (MDS).

      SECONDARY OBJECTIVES:

      I. Compare overall survival between the two schedules. II. Compare non relapse mortality
      between the two schedules. III. Compare neutrophil and platelet engraftment between the two
      schedules. IV. Compare acute and chronic graft-versus-host disease (GVHD) between the two
      schedules.

      V. Compare cumulative incidence of relapse between the two schedules. VI. Compare grade
      III/IV toxicity between the two schedules.

      TERTIARY OBJECTIVES:

      I. To study chemotherapy resistance. II. To study deoxyribonucleic acid (DNA) damage. III. To
      study immune recovery and cytokines (both in plasma and cells). IV. To study BCL-2 family
      expression, stem cell surface markers and intracellular signaling markers in AML cells at the
      time of relapse.

      OUTLINE:

      PREPARATIVE REGIMEN: Patients are randomized to 1 of 2 treatment arms.

      ARM I: Patients receive venetoclax orally (PO) once daily (QD) on days -22 to -3 and busulfan
      intravenously (IV) over 3 hours on days -13 and -12. Patients then receive fludarabine
      phosphate IV over 1 hour, cladribine IV over 2 hours, and busulfan IV over 3 hours on days -6
      to -3.

      ARM II: Patients receive venetoclax PO QD on days -22 to -3 and busulfan IV over 3 hours on
      days -20 and -13. Patients then receive fludarabine phosphate IV over 1 hour, cladribine IV
      over 2 hours, and busulfan IV over 3 hours on days -6 to -3.

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

      After completion of study treatment, patients are followed up for 2.5 years.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression free survival
time frame: At 6 months
description: The method of Kaplan and Meier will be used to estimate distribution of progression free survival.
measure: Disease free survival (DFS)
time frame: Up to 2.5 years
description: Will test whether there is strong evidence that DFS differs between the two arms using a stratified log-rank test. Will use the Lan-DeMets alpha spending approach with an O'Brien-Fleming stopping boundary to compare the two arms.
measure: Incidence of toxicity of these regimens
time frame: Up to 2.5 years
measure: Cumulative incidence of acute graft versus host disease (GVHD)
time frame: Up to 2.5 years
description: Will use the method of Gooley et al to estimate the cumulative incidence of acute GVHD. Will use the method of Fine and Gary to fit regression models to the cumulative incidence outcomes.
measure: Cumulative incidence of chronic GVHD
time frame: Up to 2.5 years
description: Will use the method of Gooley et al to estimate the cumulative incidence of chronic GVHD. Will use the method of Fine and Gary to fit regression models to the cumulative incidence outcomes.
measure: Overall survival
time frame: Up to 2.5 years
description: The method of Kaplan and Meier will be used to estimate the distribution of overall survival. Cox proportional hazards regression analysis will be used to model the association between overall survival and covariates of interest.
measure: Time to neutrophil engraftment
time frame: Up to 2.5 years
description: The method of Kaplan and Meier will be used to estimate time to neutrophil engraftment.
measure: Time to platelet engraftment
time frame: Up to 2.5 years
description: The method of Kaplan and Meier will be used to estimate time to platelet engraftment.
measure: Cumulative incidence of relapse
time frame: Up to 2.5 years
description: Will use the method of Gooley et al to estimate the cumulative incidence of relapse. Will use the method of Fine and Gary to fit regression models to the cumulative incidence outcomes.
measure: Non-relapse mortality
time frame: Up to 2.5 years
description: Will use the method of Gooley et al to estimate the cumulative incidence of non-relapse mortality. Will use the method of Fine and Gary to fit regression models to the cumulative incidence outcomes. Logistic regression will be used to model the association between 100-day NRM and clinical and demographic covariates of interest.
arm group label: Arm I (busulfan days -13 and -12 before PBSCT)
arm group type: Experimental
description: PREPARATIVE REGIMEN: Patients receive venetoclax PO QD on days -22 to -3 and busulfan IV over 3 hours on days -13 and -12. Patients then receive fludarabine phosphate IV over 1 hour, cladribine IV over 2 hours, and busulfan IV over 3 hours on days -6 to -3.
TRANSPLANT: Patients undergo allogeneic PBSCT on day 0.
arm group label: Arm II (busulfan days -20 and -13 before PBSCT)
arm group type: Experimental
description: PREPARATIVE REGIMEN: Patients receive venetoclax PO QD on days -22 to -3 and busulfan IV over 3 hours on days -20 and -13. Patients then receive fludarabine phosphate IV over 1 hour, cladribine IV over 2 hours, and busulfan IV over 3 hours on days -6 to -3.
TRANSPLANT: Patients undergo allogeneic PBSCT on day 0.
intervention type: Procedure
intervention name: Allogeneic Hematopoietic Stem Cell Transplantation
description: Undergo allogeneic PBSCT
arm group label: Arm I (busulfan days -13 and -12 before PBSCT)
arm group label: Arm II (busulfan days -20 and -13 before PBSCT)
other name: Allogeneic
other name: Allogeneic Hematopoietic Cell Transplantation
other name: Allogeneic Stem Cell Transplantation
other name: HSC
other name: HSCT
other name: Stem Cell Transplantation, Allogeneic
intervention type: Drug
intervention name: Busulfan
description: Given IV
arm group label: Arm I (busulfan days -13 and -12 before PBSCT)
arm group label: Arm II (busulfan days -20 and -13 before 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: Cladribine
description: Given IV
arm group label: Arm I (busulfan days -13 and -12 before PBSCT)
arm group label: Arm II (busulfan days -20 and -13 before PBSCT)
other name: 2-CdA
other name: 2CDA
other name: CdA
other name: Cladribina
other name: Leustat
other name: Leustatin
other name: Leustatine
other name: RWJ-26251
intervention type: Drug
intervention name: Fludarabine Phosphate
description: Given IV
arm group label: Arm I (busulfan days -13 and -12 before PBSCT)
arm group label: Arm II (busulfan days -20 and -13 before PBSCT)
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: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Arm I (busulfan days -13 and -12 before PBSCT)
arm group label: Arm II (busulfan days -20 and -13 before PBSCT)
intervention type: Procedure
intervention name: Peripheral Blood Stem Cell Transplantation
description: Undergo allogeneic PBSCT
arm group label: Arm I (busulfan days -13 and -12 before PBSCT)
arm group label: Arm II (busulfan days -20 and -13 before 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: Arm I (busulfan days -13 and -12 before PBSCT)
arm group label: Arm II (busulfan days -20 and -13 before PBSCT)
intervention type: Drug
intervention name: Venetoclax
description: Given PO
arm group label: Arm I (busulfan days -13 and -12 before PBSCT)
arm group label: Arm II (busulfan days -20 and -13 before PBSCT)
other name: ABT-0199
other name: ABT-199
other name: ABT199
other name: GDC-0199
other name: RG7601
other name: Venclexta
other name: Venclyxto
criteria: 
gender: All
minimum age: 2 Years
maximum age: 70 Years
healthy volunteers: No
last name: Uday R Popat
role: Principal Investigator
affiliation: M.D. Anderson Cancer Center
facility: 
country: United States
url: http://www.mdanderson.org
description: MD Anderson Cancer Center
responsible party type: Sponsor
mesh term: Leukemia
mesh term: Preleukemia
mesh term: Myelodysplastic Syndromes
mesh term: Syndrome
mesh term: Fludarabine
mesh term: Fludarabine phosphate
mesh term: Busulfan
mesh term: Venetoclax
mesh term: Cladribine
mesh term: 2-chloro-3'-deoxyadenosine