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Acute Myeloid LeukemiaPhase 2/3NCT04708054

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

A Phase 2/3 study testing Busulfan, Cladribine and Fludarabine Phosphate in people with Acute Myeloid Leukemia and Chronic Myelomonocytic Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 yearsHealthy volunteers can take part
What is being tested?
Busulfan, Cladribine and Fludarabine Phosphate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
324 participants
Where
1 siteUnited States
Study dates
21 Oct 2021to 31 Dec 2027
Phase
Phase 2/3
Are there results?
Not yet: the study is under way

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 18 to 70 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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)
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  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Uday R. Popat contact

713-745-3055

upopat@mdanderson.org

United States1 site, 1 recruiting

  • M D Anderson Cancer Center

    Houston, Texas, 77030

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

    Uday R. Popat

    Recruiting

Other trials in United States

About this study

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.

Read the 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 NCI toxicity criteria
  2. Time to neutrophil and platelet engraftment
  3. Incidence of acute and chronic GVHD
  4. Relapse incidence
  5. Non-relapse mortality
  6. Overall survival
  7. Graft versus host disease-relapse free survival (GRFS)

Phase 3 Portion

Primary Objective

  1. To compare progression free survival between two arms Arm 1 Standard of Care: fludarabine + IV busulfan (FluBu) versus Arm 2 Experimental: Venetoclax + Fractionated busulfan, cladribine, and fludarabine

Secondary Objectives To compare following between two arms

  1. Safety of this regimen as per NCI toxicity criteria
  2. Time to neutrophil and platelet engraftment
  3. Incidence of acute and chronic GVHD
  4. Relapse incidence
  5. Non-relapse mortality
  6. Overall survival
  7. Graft versus host disease-relapse free survival (GRFS)
Being tested
Busulfan, Cladribine, Fludarabine Phosphate, Hematopoietic Cell Transplantation, Thiotepa
Medical subject headings
Leukemia, Myeloid, Acute, Leukemia, Myelomonocytic, Chronic, Myelodysplastic Syndromes

What participants receive

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

  • 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

  • Hematopoietic Cell TransplantationProcedure or surgery

    Also called HCT, Hematopoietic Stem Cell Transplantation, HSCT, Stem Cell Transplant

    Undergo stem cell transplantation

  • ThiotepaDrug

    Also called 1,1'',1''''-Phosphinothioylidynetrisaziridine, Girostan, N,N'', N''''-Triethylenethiophosphoramide, Oncotiotepa

    Given IV

  • VenetoclaxDrug

    Also called ABT-0199, ABT-199, ABT199, GDC-0199

    Given PO

Study groups in NCT04708054
Study groupRoleWhat they receive
Treatment (venetoclax, busulfan, fludarabine, cladribine)ExperimentalPatients 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.
Receives: Drug: Busulfan; Drug: Cladribine; Drug: Fludarabine Phosphate; Procedure: Hematopoietic Cell Transplantation; Drug: Thiotepa; Drug: Venetoclax

What is being measured

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

  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.

    Measured: At 1 year post-transplant

Secondary outcomes (7)

  1. Overall survival (OS)

    OS will be calculated from the time of transplant by the method of Kaplan and Meier.

    Measured: Up to 3 years post-transplant

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

    GRFS will be calculated from the time of transplant by the method of Kaplan and Meier.

    Measured: Up to 3 years post-transplant

  3. Time to platelet engraftment

    The time to platelet engraftment will be calculated from the time of transplant and estimated by the Kaplan-Meier method.

    Measured: From the time of transplant up to 3 years

  4. Time to neutrophil engraftment

    The time to neutrophil engraftment will be calculated from the time of transplant and estimated by the Kaplan-Meier method.

    Measured: From the time of transplant up to 3 years

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

    The cumulative incidence of acute and chronic GvHD with the competing risks of relapse and death will be estimated using the method of Gooley, and the method of Fine and Gray will be used to model the association between both parameters and clinical and treatment characteristics of interest.

    Measured: Up to 3 years post-transplant

  6. Incidence of relapse and non-relapse mortality

    The cumulative incidence of non-relapse mortality and relapse will also be assessed in a competing risks framework, with similar analyses performed.

    Measured: Up to 3 years post-transplant

  7. Incidence of adverse events

    Descriptive statistics will be used to summarize adverse events. The number and proportion of subjects with treatment emergent adverse events will be reported. All other safety parameters will be summarized using descriptive statistics or frequency counts. Graphical summaries will be used where appropriate.

    Measured: Up to 3 years post-transplant

Timeline

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

  1. First posted13 Jan 2021
  2. Study start21 Oct 2021
  3. Primary completion31 Dec 2027 (estimated)
  4. Study completion31 Dec 2027 (estimated)

Resources

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 2/3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
324 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04708054
Sponsor's protocol ID
2020-0790
Other IDs
NCI-2020-13919, 2020-0790
Status last verified
Jul 2026
First submitted
12 Jan 2021
Last updated
11 Aug 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Busulfan, Cladribine and Fludarabine Phosphate in people with Acute Myeloid Leukemia and Chronic Myelomonocytic Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 49 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 11 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Uday R. Popat (713-745-3055, upopat@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

1-year progression free survival (PFS) (time frame: At 1 year post-transplant). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04708054.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2026.

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