Status:
RECRUITING
Venetoclax to Improve Outcomes of Fractionated Busulfan Regimen in Patients With High-Risk AML and MDS
Lead Sponsor:
M.D. Anderson Cancer Center
Conditions:
Acute Myeloid Leukemia
Chronic Myelomonocytic Leukemia
Eligibility:
All Genders
18-70 years
Phase:
PHASE2
PHASE3
Brief 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 ...
Detailed Description
Phase 2 Portion Primary Objective 1) To obtain preliminary evidence of efficacy as defined by 1-year progression free survival. Secondary Objectives To determine: 1. Safety of this regimen as per ...
Eligibility Criteria
Inclusion
- Inclusion Criteria:
- Phase II
- Age ≥ 18 and ≤ 70 years. English and non-English speaking patients are eligible.
- 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
- Therapy-related AML.
- 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:
- 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 ASXL1 or RUNX1
- Maximum IPSS-R \>3.5 between diagnosis and the start of the preparative regimen.
- ≥ 5% BM blasts at transplant
- Therapy-related MDS
- 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 test
- 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.
- Phase III
- Age ≥ 18 and ≤ 65 years. English and non-English speaking patients are eligible.
- Patients with acute myeloid leukemia who have previously received induction therapy and one of the following high-risk features:
- ELN22 adverse risk prognostic group irrespective of remission status (see Appendix
- Measurable residual disease positive (MRD +) including MRD + any time after induction therapy.
- 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 4 for details.
- AML secondary to MDS or MPD
- Therapy-related AML.
- Not in complete remission after one course of induction therapy
- Second or higher complete remission
- Or
- Patients with myelodysplastic syndrome and one of the following high-risk features:
- Poor or Very poor cytogenetic risk group as per IPSS-R
- Mutated P53 or Ras pathway genes (CBL, NRAS, KRAS, NF1, PTPN11) or ASXL1 or RUNX1 or moderate high, or high, or very high-risk group as per IPSS-M
- Maximum IPSS-R \>3.5 between diagnosis and the start of the preparative regimen.
- ≥ 5% BM blasts at transplant
- Therapy-related MDS
- Or
- Patients with CMML
- HLA-identical sibling or a minimum of 7/8 matched unrelated donor
- Subject must voluntarily sign an informed consent
- Female subjects of childbearing potential must have negative results for pregnancy test
- 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:
- Subject is known to be positive for HIV.
- Subject has cognitive impairments and/or is a prisoner.
- Subject has acute promyelocytic leukemia
- 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 angina;
- Corrected DLCO \< 50% 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
- 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.
- Prior allogeneic stem cell transplantation.
Exclusion
Key Trial Info
Start Date :
October 21 2021
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
December 31 2027
Estimated Enrollment :
324 Patients enrolled
Trial Details
Trial ID
NCT04708054
Start Date
October 21 2021
End Date
December 31 2027
Last Update
September 3 2025
Active Locations (1)
Enter a location and click search to find clinical trials sorted by distance.
1
M D Anderson Cancer Center
Houston, Texas, United States, 77030