- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04708054
Venetoclax to Improve Outcomes of Fractionated Busulfan Regimen in Patients With High-Risk AML and MDS
Study Overview
Status
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:
- Safety of this regimen as per NCI toxicity criteria
- Time to neutrophil and platelet engraftment
- Incidence of acute and chronic GVHD
- Relapse incidence
- Non-relapse mortality
- Overall survival
- 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
- Safety of this regimen as per NCI toxicity criteria
- Time to neutrophil and platelet engraftment
- Incidence of acute and chronic GVHD
- Relapse incidence
- Non-relapse mortality
- Overall survival
- Graft versus host disease-relapse free survival (GRFS)
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Uday R. Popat
- Phone Number: 713-745-3055
- Email: upopat@mdanderson.org
Study Locations
-
-
Texas
-
Houston, Texas, United States, 77030
- M D Anderson Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
Phase II
- Age ≥ 18 and ≤ 70 years. English and non-English speaking participants are eligible.
Participants 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 Or
Participants 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
- Participants must voluntarily sign an informed consent
- Female participants 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)
- 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.
Phase III
- Age ≥ 18 and ≤ 65 years. English and non-English speaking participants are eligible.
Participants 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 Or
Participants 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 8/8 matched unrelated donor
- Participants must voluntarily sign an informed consent
- Female participants 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)
- 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.
Exclusion criteria:
- Participants is known to be positive for HIV.
- Participants has cognitive impairments and/or is a prisoner.
- Participants has acute promyelocytic leukemia
- Participants 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: 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.
- Cardiac history of CHF requiring treatment or Ejection Fraction < 50% or unstable angina;
- Corrected DLCO < 65% 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
- Prior gemtuzumab ozogamicin and/or inotuzumab ozogamicin use
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (venetoclax, busulfan, fludarabine, cladribine)
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.
|
Given PO
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Undergo stem cell transplantation
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
1-year progression free survival (PFS)
Time Frame: At 1 year post-transplant
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival (OS)
Time Frame: Up to 3 years post-transplant
|
OS will be calculated from the time of transplant by the method of Kaplan and Meier.
|
Up to 3 years post-transplant
|
Graft-versus (vs.)-host disease-free, relapse-free survival (GRFS)
Time Frame: Up to 3 years post-transplant
|
GRFS will be calculated from the time of transplant by the method of Kaplan and Meier.
|
Up to 3 years post-transplant
|
Time to platelet engraftment
Time Frame: From the time of transplant up to 3 years
|
The time to platelet engraftment will be calculated from the time of transplant and estimated by the Kaplan-Meier method.
|
From the time of transplant up to 3 years
|
Time to neutrophil engraftment
Time Frame: From the time of transplant up to 3 years
|
The time to neutrophil engraftment will be calculated from the time of transplant and estimated by the Kaplan-Meier method.
|
From the time of transplant up to 3 years
|
Incidence of acute and chronic graft-vs.-host disease (GvHD)
Time Frame: Up to 3 years post-transplant
|
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.
|
Up to 3 years post-transplant
|
Incidence of relapse and non-relapse mortality
Time Frame: Up to 3 years post-transplant
|
The cumulative incidence of non-relapse mortality and relapse will also be assessed in a competing risks framework, with similar analyses performed.
|
Up to 3 years post-transplant
|
Incidence of adverse events
Time Frame: Up to 3 years post-transplant
|
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.
|
Up to 3 years post-transplant
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Uday R Popat, M.D. Anderson Cancer Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Disease Attributes
- Bone Marrow Diseases
- Hematologic Diseases
- Myelodysplastic-Myeloproliferative Diseases
- Leukemia, Myeloid
- Chronic Disease
- Myelodysplastic Syndromes
- Leukemia
- Leukemia, Myelomonocytic, Chronic
- Leukemia, Myelomonocytic, Juvenile
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Venetoclax
- Fludarabine
- Fludarabine phosphate
- Thiotepa
- Busulfan
- Cladribine
- 2-chloro-3'-deoxyadenosine
Other Study ID Numbers
- 2020-0790 (Other Identifier: M D Anderson Cancer Center)
- NCI-2020-13919 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Acute Myeloid Leukemia
-
University of PennsylvaniaActive, not recruitingAcute Myeloid Leukemia, in Relapse | Acute Myeloid Leukemia, Refractory | Acute Myeloid Leukemia, PediatricUnited States
-
Terrence J Bradley, MDImago BioSciences, Inc., a subsidiary of Merck & Co., Inc., (Rahway, New...RecruitingAcute Myeloid Leukemia | Refractory Acute Myeloid Leukemia | Acute Myeloid Leukemia, in RelapseUnited States
-
Bhavana BhatnagarCTI BioPharmaCompletedRecurrent Adult Acute Myeloid Leukemia | Secondary Acute Myeloid Leukemia | Untreated Adult Acute Myeloid Leukemia | Therapy-Related Acute Myeloid LeukemiaUnited States
-
Washington University School of MedicineWithdrawnRefractory Acute Myeloid Leukemia | Relapsed Acute Myeloid LeukemiaUnited States
-
C. Babis AndreadisGateway for Cancer Research; AVEO Pharmaceuticals, Inc.TerminatedAcute Myeloid Leukemia | Refractory Acute Myeloid Leukemia | Relapsed Acute Myeloid LeukemiaUnited States
-
National Cancer Institute (NCI)RecruitingAcute Myeloid Leukemia | Secondary Acute Myeloid Leukemia | Recurrent Acute Myeloid Leukemia | Refractory Acute Myeloid LeukemiaUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI)RecruitingAcute Myeloid Leukemia | Recurrent Adult Acute Myeloid Leukemia | Secondary Acute Myeloid Leukemia | Refractory Acute Myeloid LeukemiaUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI)Active, not recruitingAcute Myeloid Leukemia | Secondary Acute Myeloid Leukemia | Untreated Adult Acute Myeloid Leukemia | Recurrent Acute Myeloid Leukemia | Refractory Acute Myeloid Leukemia | Therapy-Related Acute Myeloid LeukemiaUnited States
-
Massachusetts General HospitalExelixisCompletedRefractory Acute Myeloid Leukemia | Relapsed Acute Myeloid LeukemiaUnited States
-
Jacqueline Garcia, MDEli Lilly and CompanyCompletedCombination Merestinib and LY2874455 for Patients With Relapsed or Refractory Acute Myeloid LeukemiaRelapsed Adult Acute Myeloid Leukemia | Refractory Adult Acute Myeloid LeukemiaUnited States
Clinical Trials on Venetoclax
-
Virginia Commonwealth UniversityAbbVieWithdrawnRelapsed Small Cell Lung Cancer | Refractory Small Cell Lung Carcinoma
-
PrECOG, LLC.Genentech, Inc.CompletedFollicular Lymphoma | Non-Hodgkin's Lymphoma Follicular | Non-Hodgkin's Lymphoma, Adult High GradeUnited States
-
University of Maryland, BaltimoreActive, not recruitingRelapsed or Refractory Acute Myeloid LeukemiaUnited States
-
Yale UniversityCompleted
-
Gruppo Italiano Malattie EMatologiche dell'AdultoRecruiting
-
Stichting Hemato-Oncologie voor Volwassenen NederlandNordic Lymphoma GroupActive, not recruiting
-
Stichting Hemato-Oncologie voor Volwassenen NederlandNordic CLL Study GroupActive, not recruitingChronic Lymphocytic Leukemia in Relapse | Chronic Lymphocytic Leukemia in RemissionNetherlands, Belgium, Denmark, Finland, Norway, Sweden
-
BioSight Ltd.Recruiting
-
The Lymphoma Academic Research OrganisationInstitute of Cancer Research, United KingdomRecruitingMantle Cell LymphomaFrance, United Kingdom, Belgium
-
National Heart, Lung, and Blood Institute (NHLBI)RecruitingChronic Lymphocytic LeukemiaUnited States