Venetoclax and Sequential Busulfan, Cladribine, and Fludarabine Phosphate Before Donor Stem Cell Transplant in Treating Patients With Acute Myelogenous Leukemia or Myelodysplastic Syndrome

NCT02250937 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2014-0431NCI-2014-02324
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized phase II trial studies how well venetoclax and sequential busulfan, cladribine, and fludarabine phosphate before donor stem cell transplant work in treating patients with acute myelogenous leukemia or myelodysplastic syndrome. Giving chemotherapy before a donor peripheral blood stem cell transplant helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. When the healthy stem cells from a donor are infused into a patient, they may help the patient's bone marrow make more healthy cells and platelets and may help destroy any remaining cancer cells.

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (2)

• Progression free survival

  The method of Kaplan and Meier will be used to estimate distribution of progression free survival.

  At 6 months

• Disease free survival (DFS)

  Will test whether there is strong evidence that DFS differs between the two arms using a stratified log-rank test. Will use the Lan-DeMets alpha spending approach with an O'Brien-Fleming stopping boundary to compare the two arms.

  Up to 2.5 years

Secondary Outcomes (8)

• Incidence of toxicity of these regimens

  Up to 2.5 years

• Cumulative incidence of acute graft versus host disease (GVHD)

  Up to 2.5 years

• Cumulative incidence of chronic GVHD

  Up to 2.5 years

• Overall survival

  Up to 2.5 years

• Time to neutrophil engraftment

  Up to 2.5 years

Study Arms (2)

Arm I (busulfan days -13 and -12 before PBSCT)

EXPERIMENTAL

PREPARATIVE REGIMEN: Patients receive venetoclax PO QD on days -22 to -3 and busulfan IV over 3 hours on days -13 and -12. Patients then receive fludarabine phosphate IV over 1 hour, cladribine IV over 2 hours, and busulfan IV over 3 hours on days -6 to -3. TRANSPLANT: Patients undergo allogeneic PBSCT on day 0.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Busulfan; Drug: Cladribine; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Procedure: Peripheral Blood Stem Cell Transplantation; Other: Pharmacological Study; Drug: Venetoclax

Arm II (busulfan days -20 and -13 before PBSCT)

EXPERIMENTAL

PREPARATIVE REGIMEN: Patients receive venetoclax PO QD on days -22 to -3 and busulfan IV over 3 hours on days -20 and -13. Patients then receive fludarabine phosphate IV over 1 hour, cladribine IV over 2 hours, and busulfan IV over 3 hours on days -6 to -3. TRANSPLANT: Patients undergo allogeneic PBSCT on day 0.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Busulfan; Drug: Cladribine; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Procedure: Peripheral Blood Stem Cell Transplantation; Other: Pharmacological Study; 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

Arm I (busulfan days -13 and -12 before PBSCT); Arm II (busulfan days -20 and -13 before PBSCT)

Cladribine DRUG

Given IV

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

Arm I (busulfan days -13 and -12 before PBSCT); Arm II (busulfan days -20 and -13 before PBSCT)

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

Arm I (busulfan days -13 and -12 before PBSCT); Arm II (busulfan days -20 and -13 before PBSCT)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (busulfan days -13 and -12 before PBSCT); Arm II (busulfan days -20 and -13 before PBSCT)

Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo allogeneic PBSCT

Also known as: PBPC transplantation, PBSCT, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplant, Peripheral Stem Cell Transplantation

Arm I (busulfan days -13 and -12 before PBSCT); Arm II (busulfan days -20 and -13 before PBSCT)

Pharmacological Study OTHER

Correlative studies

Arm I (busulfan days -13 and -12 before PBSCT); Arm II (busulfan days -20 and -13 before PBSCT)

Venetoclax DRUG

Given PO

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

Arm I (busulfan days -13 and -12 before PBSCT); Arm II (busulfan days -20 and -13 before PBSCT)

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo allogeneic PBSCT

Also known as: Allogeneic, Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT, Stem Cell Transplantation, Allogeneic

Arm I (busulfan days -13 and -12 before PBSCT); Arm II (busulfan days -20 and -13 before PBSCT)

Eligibility Criteria

• Age: 2 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with biopsy-proven acute myeloid leukemia or myelodysplastic syndrome with persistent disease or in remission
• Human leukocyte antigen (HLA)-identical sibling or 8/8 matched unrelated donor transplant
• Patients age 18 to 70 years old; eligibility for pediatric patients will be determined in conjunction with an MD Anderson Cancer Center (MDACC) pediatrician; patients age 2-17 years may be enrolled after at least 10 adults (ages 18-70 years old) have been assessed for safety at day 30
• Direct bilirubin \< 1 mg/dl
• Alanine aminotransferase (ALT) \< 3 times upper limit of normal
• Creatinine clearance \> 50 ml/min (calculated creatinine clearance is permitted)
• Forced expiratory volume in 1 second (FEV1) \>= 50% of expected corrected for hemoglobin and/or volume
• Forced vital capacity (FVC) \>= 50% of expected corrected for hemoglobin and/or volume
• Diffusing capacity of the lungs for carbon monoxide (DLCO) \>= 50% of expected corrected for hemoglobin and/or volume
• Children unable to perform pulmonary function tests (e.g., less than 7 years old) pulse oximetry of \>= 92% on room air
• Left ventricular ejection fraction (LVEF) \>= 40%
• Patient, legally authorized representative (LAR), or parent able to sign informed consent; able to give assent for patients age 7-17
• Negative beta human chorionic gonadotropin (HCG) test in a woman with child bearing potential, defined as not post-menopausal for 12 months or no previous surgical sterilization; women of child bearing potential must be willing to use an effective contraceptive measure while on study
• Performance score of \>= 70 by Karnofsky/Lansky or performance status (PS) 0 or 1 (Eastern Cooperative Oncology Group \[ECOG\] =\< 1)

You may not qualify if:

• Prior allogeneic or autologous transplantation
• Uncontrolled infections
• Human immunodeficiency virus (HIV) seropositivity
• Hematopoietic cell transplantation (HCT) co-morbidity index score \> 3; the principal investigator is the final arbiter of eligibility for comorbidity score \> 3
• Patients with prior coronary artery disease

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

Stem Cell Transplantation; Busulfan; Cladribine; fludarabine phosphate; Peripheral Blood Stem Cell Transplantation; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; 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; Hematopoietic Stem Cell Transplantation

Study Officials

• Uday R Popat

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 24, 2014
• First Posted: September 26, 2014
• Study Start: October 27, 2014
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): October 31, 2027
• Last Updated: April 15, 2026

Record last verified: 2026-04

Locations

US (1)