Venetoclax to Improve Outcomes of Fractionated Busulfan Regimen in Patients With High-Risk AML and MDS VENETOCLAX AS PART OF PRE-TRANSPLANT CHEMOTHERAPY

What's the purpose of this trial?

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.

This trial is currently open and accepting patients.


What will happen during the trial?

You may be able to join this trial if you:

The following criteria is a partial list of reasons why patients may be eligible to participate in this clinical trial. Further evaluation with a medical professional is required.

Inclusion Criteria:

Non-English speaking patients are eligible.

1. Age ≥ 18 and ≤ 70 years. English and non-English speaking patients are eligible.
2. Patients with acute myeloid leukemia who have previously received induction therapy and one of the following high-risk features:

1. ELN17 adverse risk prognostic group irrespective of remission status (see Appendix 2).
2. Measurable residual disease positive (MRD +)
3. 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.
4. AML secondary to MDS or MPD.
5. Therapy-related AML.
6. Not in complete remission after one course of induction therapy

Or

Patients with myelodysplastic syndrome or CMML and one of the following high-risk features:
1. Poor or Very poor cytogenetic risk group as per IPSS-R
2. Mutated P53 or Ras pathway genes (CBL, NRAS, KRAS, NF1, PTPN11) or ASXL1 or RUNX1
3. Maximum IPSS-R \>3.5 between diagnosis and the start of the preparative regimen.
4. ≥ 5% BM blasts at transplant
5. Therapy-related MDS or patients with CMML
3. HLA-identical sibling or a minimum of 7/8 matched unrelated donor, or a haploidentical related donor available
4. Subject must voluntarily sign an informed consent
5. Female subjects of childbearing potential must have negative results for pregnancy test
6. 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 24 hours urine collection.

Exclusion criteria:

1. Subject is known to be positive for HIV.
2. Subject has cognitive impairments and/or is a prisoner.
3. Subject has acute promyelocytic leukemia
4. Subject has known active CNS involvement with AML.
5. 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
6. Cardiac history of CHF requiring treatment or Ejection Fraction \< 50% or unstable angina;
7. Corrected DLCO \< 65% or FEV1 \< 65%;
8. 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
9. Prior gemtuzumab ozogamicin and/or inotuzumab ozogamicin use
10. Patients with cognitive impairments and/or any serious unstable pre-existing medical condition or psychiatric disorder that can interfere with safety or with obtaining informed consent or compliance with study procedures.
11. Prior autologous or allogeneic stem cell transplantation.


Additional Trial Information

Phase 2

Enrollment: 324 patients (estimated)

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Trial Locations

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Texas

MD Anderson Cancer Center The University of Texas

Houston, TX

Open and Accepting
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