Venetoclax, Busulfan, Cladribine, and Fludarabine for the Treatment of High-Risk Acute Myeloid Leukemia or Myelodysplastic Syndrome

• Status: Not yet recruiting
• Trial end date: 2021-12-31
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Treatments: 2-chloro-3'-deoxyadenosine; Busulfan; Cladribine; Fludarabine; Fludarabine phosphate; Thiotepa; Venetoclax

Criteria

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

• Measurable residual disease positive (MRD +)

• Not in complete remission including complete remission without count recovery (Cri), primary refractory, or relapsed disease or

Patients with myelodysplastic syndrome or chronic myelomonocytic leukemia (CMML) and one of the following high-risk features:

• Poor or very poor cytogenetic risk group as per Revised International Prognostic Scoring System (IPSS-R)

• Mutated P53 or Ras pathway genes (CBL, NRAS, KRAS, NF1, PTPN1) or DNMT 3a or ASXL1 or RUNX1

• IPSS-R > 3.5 at diagnosis

• >= 5% bone marrow (BM) blasts at transplant

• HLA-identical sibling or a 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 test

• Aspartate transaminase (AST) and alanine transaminase (ALT) < 3.0 x upper limit of normal (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:

• Subject is known to be positive for human immunodeficiency virus (HIV)

• Subject has acute promyelocytic leukemia

• Subject has known active central nervous system (CNS) involvement with acute myeloblastic leukemia (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 (hepatitis C virus [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 congestive heart failure (CHF) requiring treatment or ejection fraction < 50% or unstable angina

• Corrected diffusion capacity of the lung for carbon monoxide (DLCO) < 65% or forced expiratory volume in 1 second (FEV1) < 65%

• Treatment with any of the following within 7 days prior to the first dose of study drug:

• Steroid therapy for anti-neoplastic intent

• Moderate or strong cytochrome P450 3A (CYP3A) inhibitors, moderate or strong CYP3A inducers. These agents may be used once venetoclax is discontinued

• 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