RECRUITING

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

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Conditions

Acute Myeloid LeukemiaChronic Myelomonocytic LeukemiaMyelodysplastic Syndrome

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2021-10-21
Study Completion:2027-12-31
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT04708054

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 70 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. 1. Age ≥ 18 and ≤ 70 years. English and non-English speaking participants are eligible.
  2. 2. Participants with acute myeloid leukemia who have previously received induction therapy and one of the following high-risk features:
  3. 1. ELN17 adverse risk prognostic group irrespective of remission status (see Appendix 2).
  4. 2. Measurable residual disease positive (MRD +)
  5. 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.
  6. 4. AML secondary to MDS or MPD
  7. 5. Therapy-related AML.
  8. 6. Not in complete remission after one course of induction therapy Or
  9. 1. Poor or Very poor cytogenetic risk group as per IPSS-R
  10. 2. Mutated P53 or Ras pathway genes (CBL, NRAS, KRAS, NF1, PTPN1) or DNMT 3a or ASXL1 or RUNX1
  11. 3. Maximum IPSS-R \>3.5 between diagnosis and the start of the preparative regimen.
  12. 4. ≥ 5% BM blasts at transplant
  13. 5. Therapy-related MDS
  14. 3. HLA-identical sibling or a minimum of 7/8 matched unrelated donor, or a haploidentical related donor available
  15. 4. Participants must voluntarily sign an informed consent
  16. 5. Female participants of childbearing potential must have negative results for pregnancy test
  17. 6. Adequate hepatic and renal function per local laboratory reference range as follows:
  18. * Aspartate transaminase (AST) and alanine transaminase (ALT) \< 3.0X ULN
  19. * Bilirubin \<1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
  20. * Participants 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.
  21. 1. Age ≥ 18 and ≤ 65 years. English and non-English speaking participants are eligible.
  22. 2. Participants with acute myeloid leukemia who have previously received induction therapy and one of the following high-risk features:
  23. 1. ELN22 adverse risk prognostic group irrespective of remission status (see Appendix 3).
  24. 2. Measurable residual disease positive (MRD +)
  25. 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 4 for details.
  26. 4. AML secondary to MDS or MPD
  27. 5. Therapy-related AML.
  28. 6. Not in complete remission after one course of induction therapy
  29. 7. Second or higher complete remission Or
  30. 1. Poor or Very poor cytogenetic risk group as per IPSS-R
  31. 2. 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
  32. 3. Maximum IPSS-R \>3.5 between diagnosis and the start of the preparative regimen.
  33. 4. ≥ 5% BM blasts at transplant
  34. 5. Therapy-related MDS Or Patients with CMML
  35. 3. HLA-identical sibling or a minimum of 7/8 matched unrelated donor
  36. 4. Participants must voluntarily sign an informed consent
  37. 5. Female participants of childbearing potential must have negative results for pregnancy test
  38. 6. Adequate hepatic and renal function per local laboratory reference range as follows:
  39. * Aspartate transaminase (AST) and alanine transaminase (ALT) \< 3.0X ULN
  40. * Bilirubin \<1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
  41. * Participants 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.
  1. 1. Participants is known to be positive for HIV.
  2. 2. Participants has cognitive impairments and/or is a prisoner.
  3. 3. Participants has acute promyelocytic leukemia
  4. 4. Participants has known active CNS involvement with AML.
  5. 5. Evidence of other clinically significant uncontrolled condition(s) including, but not limited to:
  6. 1. Uncontrolled and/or active systemic infection (viral, bacterial or fungal)
  7. 2. Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. Note: participants 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.
  8. 6. Cardiac history of CHF requiring treatment or Ejection Fraction \< 50% or unstable angina;
  9. 7. Corrected DLCO \< 50% or FEV1 \< 65%;
  10. 8. Administration or consumption of any of the following within 3 days prior to the first dose of study drug:
  11. * grapefruit or grapefruit products
  12. * Seville oranges (including marmalade containing Seville oranges)
  13. * star fruit
  14. 9. Participants 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.
  15. 10. Prior allogeneic stem cell transplantation.

Contacts and Locations

Study Contact

Uday R. Popat
CONTACT
713-745-3055
upopat@mdanderson.org

Principal Investigator

Uday R Popat
PRINCIPAL_INVESTIGATOR
M.D. Anderson Cancer Center

Study Locations (Sites)

M D Anderson Cancer Center
Houston, Texas, 77030
United States

Collaborators and Investigators

Sponsor: M.D. Anderson Cancer Center

  • Uday R Popat, PRINCIPAL_INVESTIGATOR, M.D. Anderson Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-10-21
Study Completion Date2027-12-31

Study Record Updates

Study Start Date2021-10-21
Study Completion Date2027-12-31

Terms related to this study

Additional Relevant MeSH Terms

  • Acute Myeloid Leukemia
  • Chronic Myelomonocytic Leukemia
  • Myelodysplastic Syndrome