Venetoclax and Sequential Busulfan Cladribine and Fludarabine Phosphate Before Donor Stem Cell Transplant in Treating Patients With Acute Myelogenous Leukemia or Myelodysplastic Syndrome

  • End date
    Oct 31, 2022
  • participants needed
  • sponsor
    M.D. Anderson Cancer Center
Updated on 15 February 2021
myeloid leukemia
blood stem cell transplant
white blood cell count
carbon monoxide
ejection fraction
direct bilirubin
cell transplantation
bone marrow procedure
human chorionic gonadotropin
conjugated bilirubin


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.



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).


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.


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.


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.

Condition Bone marrow disorder, Preleukemia, Acute myeloid leukemia, MYELODYSPLASTIC SYNDROME, Myelodysplastic Syndromes (MDS), Acute Myelogenous Leukemia (AML), Acute Myeloid Leukemia in Remission, myelodysplastic syndromes, myelodysplastic syndrome (mds), acute myelogenous leukemia, anll, acute myeloblastic leukemia
Treatment G-CSF, cyclophosphamide, fludarabine phosphate, methotrexate, laboratory biomarker analysis, busulfan, allogeneic hematopoietic stem cell transplantation, peripheral blood stem cell transplantation, Fludarabine, cladribine, Stem Cell Transplant, pharmacological study, venetoclax
Clinical Study IdentifierNCT02250937
SponsorM.D. Anderson Cancer Center
Last Modified on15 February 2021


Yes No Not Sure

Inclusion Criteria

Patients with biopsy-proven acute myeloid leukemia or myelodysplastic syndrome with persistent disease or in remission
Human leukocyte antigen (HLA)-identical sibling or 8/8 matched unrelated donor transplant
Patients age 18 to 70 years old; eligibility for pediatric patients will be determined in conjunction with an MD Anderson Cancer Center (MDACC) pediatrician; patients age 2-17 years may be enrolled after at least 10 adults (ages 18-70 years old) have been assessed for safety at day 30
Direct bilirubin < 1 mg/dl
Alanine aminotransferase (ALT) < 3 times upper limit of normal
Creatinine clearance > 50 ml/min (calculated creatinine clearance is permitted)
Forced expiratory volume in 1 second (FEV1) >= 50% of expected corrected for hemoglobin and/or volume
Forced vital capacity (FVC) >= 50% of expected corrected for hemoglobin and/or volume
Diffusing capacity of the lungs for carbon monoxide (DLCO) >= 50% of expected corrected for hemoglobin and/or volume
Children unable to perform pulmonary function tests (e.g., less than 7 years old) pulse oximetry of >= 92% on room air
Left ventricular ejection fraction (LVEF) >= 40%
Patient, legally authorized representative (LAR), or parent able to sign informed consent; able to give assent for patients age 7-17
Negative beta human chorionic gonadotropin (HCG) test in a woman with child bearing potential, defined as not post-menopausal for 12 months or no previous surgical sterilization; women of child bearing potential must be willing to use an effective contraceptive measure while on study
Performance score of >= 70 by Karnofsky/Lansky or performance status (PS) 0 or 1 (Eastern Cooperative Oncology Group [ECOG] =< 1)

Exclusion Criteria

Prior allogeneic or autologous transplantation
Uncontrolled infections
Human immunodeficiency virus (HIV) seropositivity
Hematopoietic cell transplantation (HCT) co-morbidity index score > 3; the principal investigator is the final arbiter of eligibility for comorbidity score > 3
Patients with prior coronary artery disease
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