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

NCT04708054 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2020-0790NCI-2020-13919
• Study Type: interventional
• Target: 324
• Locations: 1 country
• Sites: 1

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 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.

Conditions

Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia; Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (1)

• 1-year progression free survival (PFS)

  The proportion of patients who are alive without disease relapse (PFS) at one year will be reported along with the corresponding 95% credible interval. Cox proportional hazards regression will be used to assess the association between PFS and clinical and treatment covariates of interest.

  At 1 year post-transplant

Secondary Outcomes (7)

• Overall survival (OS)

  Up to 3 years post-transplant

• Graft-versus (vs.)-host disease-free, relapse-free survival (GRFS)

  Up to 3 years post-transplant

• Time to platelet engraftment

  From the time of transplant up to 3 years

• Time to neutrophil engraftment

  From the time of transplant up to 3 years

• Incidence of acute and chronic graft-vs.-host disease (GvHD)

  Up to 3 years post-transplant

Study Arms (1)

Treatment (venetoclax, busulfan, fludarabine, cladribine)

EXPERIMENTAL

Patients receive venetoclax PO QD on days -22 to -3, busulfan IV over 3 hours on days -20, -13, -6, -5, -4, and -3, and fludarabine phosphate 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.

Drug: Busulfan; Drug: Cladribine; Drug: Fludarabine Phosphate; Procedure: Hematopoietic Cell Transplantation; Drug: Thiotepa; Drug: Venetoclax

Interventions

Busulfan DRUG

Given IV

Also known as: 1, 4-Bis[methanesulfonoxy]butane, BUS, Bussulfam, Busulfanum, Busulfex, Busulphan, CB 2041, CB-2041, Glyzophrol, GT 41, GT-41, Joacamine, Methanesulfonic Acid Tetramethylene Ester, Methanesulfonic acid, tetramethylene ester, Mielucin, Misulban, Misulfan, Mitosan, Myeleukon, Myeloleukon, Myelosan, Mylecytan, Myleran, Sulfabutin, Tetramethylene Bis(methanesulfonate), Tetramethylene bis[methanesulfonate], WR-19508

Treatment (venetoclax, busulfan, fludarabine, cladribine)

Cladribine DRUG

Given IV

Also known as: 2-CdA, 2CDA, CdA, Cladribina, Leustat, Leustatin, Leustatine, RWJ-26251

Treatment (venetoclax, busulfan, fludarabine, cladribine)

Fludarabine Phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586

Treatment (venetoclax, busulfan, fludarabine, cladribine)

Hematopoietic Cell Transplantation PROCEDURE

Undergo stem cell transplantation

Also known as: HCT, Hematopoietic Stem Cell Transplantation, HSCT, Stem Cell Transplant, stem cell transplantation

Treatment (venetoclax, busulfan, fludarabine, cladribine)

Thiotepa DRUG

Given IV

Also known as: 1,1'',1''''-Phosphinothioylidynetrisaziridine, Girostan, N,N'', N''''-Triethylenethiophosphoramide, Oncotiotepa, STEPA, Tepadina, TESPA, Tespamin, Tespamine, Thio-Tepa, Thiofosfamide, Thiofozil, Thiophosphamide, Thiophosphoramide, Thiotef, Tifosyl, TIO TEF, Tio-tef, Triethylene Thiophosphoramide, Triethylenethiophosphoramide, Tris(1-aziridinyl)phosphine sulfide, TSPA, WR 45312

Treatment (venetoclax, busulfan, fludarabine, cladribine)

Venetoclax DRUG

Given PO

Also known as: ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto

Treatment (venetoclax, busulfan, fludarabine, cladribine)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes

Interventions

Busulfan; Cladribine; fludarabine phosphate; Stem Cell Transplantation; Hematopoietic Stem Cell Transplantation; Thiotepa; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; 2-Chloroadenosine; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxyadenosines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Phosphoramides; Organophosphorus Compounds; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring

Study Officials

• Uday R Popat

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Uday R. Popat

CONTACT

713-745-3055; upopat@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2021
• First Posted: January 13, 2021
• Study Start: October 21, 2021
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: February 19, 2026

Record last verified: 2026-02

Locations

US (1)