Acute Myeloid LeukemiaPhase 2NCT02250937

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

A Phase 2 study testing Allogeneic Hematopoietic Stem Cell Transplantation, Busulfan and Cladribine in people with Acute Myeloid Leukemia and Myelodysplastic Syndrome, run by M.D. Anderson Cancer Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

Who is it for?: Ages 2 to 70 years
Conditions the study is for: Acute Myeloid Leukemia, Myelodysplastic Syndrome
What is being tested?: Allogeneic Hematopoietic Stem Cell Transplantation, Busulfan and Cladribine
Type of treatment: Injection or infusion, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 116 participants
Where: 1 siteUnited States
Study dates: 27 Oct 2014to 31 Oct 2027
Phase: Phase 2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 2 to 70 years
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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)

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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)

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

M D Anderson Cancer Center
Houston, Texas, 77030

Other trials in United States

About this study

Official title: Allogeneic Transplantation Using Venetoclax, Timed Sequential Busulfan,Cladribine, and Fludarabine Conditioning in Patients With AML and MDS

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.

Read the detailed description

PRIMARY OBJECTIVE:

To compare progression free survival of two schedules of venetoclax, timed sequential busulfan, cladribine and fludarabine conditioning regimen in patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS).

SECONDARY OBJECTIVES:

Compare overall survival between the two schedules. II. Compare non relapse mortality between the two schedules. III. Compare neutrophil and platelet engraftment between the two schedules. IV. Compare acute and chronic graft-versus-host disease (GVHD) between the two schedules.
Compare cumulative incidence of relapse between the two schedules. VI. Compare grade III/IV toxicity between the two schedules.

TERTIARY OBJECTIVES:

To study chemotherapy resistance. II. To study deoxyribonucleic acid (DNA) damage. III. To study immune recovery and cytokines (both in plasma and cells). IV. To study BCL-2 family expression, stem cell surface markers and intracellular signaling markers in AML cells at the time of relapse.

OUTLINE:

PREPARATIVE REGIMEN: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive venetoclax orally (PO) once daily (QD) on days -22 to -3 and busulfan intravenously (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.

ARM II: 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 peripheral blood stem cell transplant (PBSCT) on day 0.

After completion of study treatment, patients are followed up for 2.5 years.

Conditions: Acute Myeloid Leukemia, Myelodysplastic Syndrome
Being tested: Allogeneic Hematopoietic Stem Cell Transplantation, Busulfan, Cladribine, Fludarabine Phosphate, Laboratory Biomarker Analysis
Medical subject headings: Leukemia, Myeloid, Acute, Myelodysplastic Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Allogeneic Hematopoietic Stem Cell TransplantationProcedure or surgery
Also called Allogeneic, Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC
Undergo allogeneic PBSCT
BusulfanDrug
Also called 1, 4-Bis[methanesulfonoxy]butane, BUS, Bussulfam, Busulfanum
Given IV
CladribineDrug
Also called 2-CdA, 2CDA, CdA, Cladribina
Given IV
Fludarabine PhosphateDrug
Also called 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara
Given IV
Laboratory Biomarker AnalysisOther
Correlative studies
Peripheral Blood Stem Cell TransplantationProcedure or surgery
Also called PBPC transplantation, PBSCT, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support
Undergo allogeneic PBSCT
Pharmacological StudyOther
Correlative studies
VenetoclaxDrug
Also called ABT-0199, ABT-199, ABT199, GDC-0199
Given PO

Study groups in NCT02250937
Study group	Role	What they receive
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. Receives: 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. Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

Progression free survival
The method of Kaplan and Meier will be used to estimate distribution of progression free survival.
Measured: 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.
Measured: Up to 2.5 years

Secondary outcomes (8)

Incidence of toxicity of these regimens
Measured: Up to 2.5 years
Cumulative incidence of acute graft versus host disease (GVHD)
Will use the method of Gooley et al to estimate the cumulative incidence of acute GVHD. Will use the method of Fine and Gary to fit regression models to the cumulative incidence outcomes.
Measured: Up to 2.5 years
Cumulative incidence of chronic GVHD
Will use the method of Gooley et al to estimate the cumulative incidence of chronic GVHD. Will use the method of Fine and Gary to fit regression models to the cumulative incidence outcomes.
Measured: Up to 2.5 years
Overall survival
The method of Kaplan and Meier will be used to estimate the distribution of overall survival. Cox proportional hazards regression analysis will be used to model the association between overall survival and covariates of interest.
Measured: Up to 2.5 years
Time to neutrophil engraftment
The method of Kaplan and Meier will be used to estimate time to neutrophil engraftment.
Measured: Up to 2.5 years
Time to platelet engraftment
The method of Kaplan and Meier will be used to estimate time to platelet engraftment.
Measured: Up to 2.5 years
Cumulative incidence of relapse
Will use the method of Gooley et al to estimate the cumulative incidence of relapse. Will use the method of Fine and Gary to fit regression models to the cumulative incidence outcomes.
Measured: Up to 2.5 years
Non-relapse mortality
Will use the method of Gooley et al to estimate the cumulative incidence of non-relapse mortality. Will use the method of Fine and Gary to fit regression models to the cumulative incidence outcomes. Logistic regression will be used to model the association between 100-day NRM and clinical and demographic covariates of interest.
Measured: Up to 2.5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

27 Oct 201431 Oct 2027

First posted26 Sep 2014 (estimated)
Study start27 Oct 2014
Primary completion31 Oct 2027 (estimated)
Study completion31 Oct 2027 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 116 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02250937
Sponsor's protocol ID: 2014-0431
Other IDs: NCI-2014-02324, 2014-0431
Status last verified: Oct 2026
First submitted: 24 Sep 2014
Last updated: 6 Oct 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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