Venetoclax to Improve Outcomes of Fractionated Busulfan Regimen in Patients With High-Risk AML and MDS

  • End date
    Dec 31, 2024
  • participants needed
  • sponsor
    M.D. Anderson Cancer Center
Updated on 28 October 2022
myeloid leukemia
cell transplantation
gilbert's syndrome
residual tumor
blast cells


This phase II trial studies the effect of venetoclax together with busulfan, cladribine, and fludarabine in treating patients with high-risk acute myeloid leukemia or myelodysplastic syndrome who are undergoing stem cell transplant. Chemotherapy drugs, such as venetoclax, busulfan, cladribine, and fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Adding venetoclax to the current standard of care stem cell transplant regimen of busulfan, fludarabine, and cladribine may help to control high-risk acute myeloid leukemia or myelodysplastic syndrome.



I. To obtain preliminary evidence of efficacy as defined by 1-year progression free survival.


I.To determine safety of this regimen as per National Cancer Institute (NCI) toxicity criteria.

II.To determine time to neutrophil and platelet engraftment. III.To determine incidence of acute and chronic graft versus host disease (GVHD).

IV.To determine relapse incidence. V.To determine non-relapse mortality. VI.To determine overall survival. VII.To determine graft versus host disease-relapse free survival (GRFS).


Patients receive venetoclax orally (PO) once daily (QD) on days -22 to -3, busulfan intravenously (IV) over 3 hours on days -20, -13, -6, -5, -4, and -3, and fludarabine phosphate (fludarabine) IV over 1 hour and cladribine IV over 2 hours on days -6 to -3 in the absence of disease progression or unacceptable toxicity. Patients then undergo stem cell transplantation over 1-2 hours on day 0.

After completion of study treatment, patients are followed up at 7 days, at engraftment, at 1, 3, 6, and 12 months, then annually for up to 3 years.

Condition Acute Myeloid Leukemia, Chronic Myelomonocytic Leukemia, Myelodysplastic Syndrome
Treatment fludarabine phosphate, busulfan, cladribine, Hematopoietic Cell Transplantation, thiotepa, venetoclax
Clinical Study IdentifierNCT04708054
SponsorM.D. Anderson Cancer Center
Last Modified on28 October 2022


Yes No Not Sure

Inclusion Criteria

Age ≥ 18 and ≤ 70 years
Patients with acute myeloid leukemia who have previously received induction therapy and one of the following high-risk features
ELN17 adverse risk prognostic group irrespective of remission status (see Appendix 2)
Measurable residual disease positive (MRD +)
Not in complete remission including complete remission without count recovery (Cri) and/or morphologic leukemia free state (MLFS), primary refractory, or relapsed disease. See Appendix 3 for details
AML secondary to MDS or MPD
Patients with myelodysplastic syndrome or CMML and one of the following high-risk
Poor or Very poor cytogenetic risk group as per IPSS-R
Mutated P53 or Ras pathway genes (CBL, NRAS, KRAS, NF1, PTPN1) or DNMT 3a or
Maximum IPSS-R >3.5 between diagnosis and the start of the preparative regimen
≥ 5% BM blasts at transplant
HLA-identical sibling or a minimum of 7/8 matched unrelated donor, or a haploidentical
related donor available
Subject must voluntarily sign an informed consent
Female subjects of childbearing potential must have negative results for pregnancy
Adequate hepatic and renal function per local laboratory reference range as follows
Aspartate transaminase (AST) and alanine transaminase (ALT) < 3.0X ULN
Bilirubin <1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of
non-hepatic origin)
Subject must have adequate renal function as demonstrated by a creatinine
clearance ≥ 50 mL/min; calculated by the Cockcroft Gault formula or measured by
hours urine collection

Exclusion Criteria

Subject is known to be positive for HIV
Subject has acute promyelocytic leukemia
Subject has cognitive impairments and/or is a prisoner
Subject has known active CNS involvement with AML
Evidence of other clinically significant uncontrolled condition(s) including, but not
limited to
Uncontrolled and/or active systemic infection (viral, bacterial or fungal)
Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. Note
subjects with serologic evidence of prior vaccination to HBV (i.e. hepatitis B
surface (HBs) antigen negative-, anti-HBs antibody positive and anti-hepatitis B
core (HBc) antibody negative) or positive anti-HBc antibody from intravenous
immunoglobulins (IVIG) may participate
Cardiac history of CHF requiring treatment or Ejection Fraction < 50% or unstable
Corrected DLCO < 65% or FEV1 < 65%
Administration or consumption of any of the following within 3 days prior to the first
dose of study drug
grapefruit or grapefruit products
Seville oranges (including marmalade containing Seville oranges)
star fruit
Prior gemtuzumab ozogamicin and/or inotuzumab ozogamicin use
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