A multicenter, open-label, randomized, phase 2 study of venetoclax and azacitidine plus cusatuzumab versus venetoclax and azacitidine alone in newly diagnosed AML patients who are not candidates for intensive therapy
- Conditions
- Acute myeloid leukemia
- Registration Number
- 2024-510991-19-00
- Lead Sponsor
- Oncoverity Inc.
- Brief Summary
To determine the efficacy of adding cusatuzumab to venetoclax plus azacitidine (VAC) compared to venetoclax plus azacitidine (VA) alone
- Detailed Description
This is a randomized, open-label, multicenter, Phase 2 trial to evaluate the efficacy, safety, and pharmacodynamics of cusatuzumab in combination with venetoclax and azacitidine compared to venetoclax and azacitidine in persons with newly diagnosed AML who are deemed ineligible for intensive chemotherapy.
Potential participants will be considered ineligible for intensive chemotherapy and, therefore, eligible for the study, if they meet the trial eligibility criteria. Potential participants will undergo a diagnostic bone marrow biopsy and aspirate collected for pathology review, cytogenetics, fluorescence in situ hybridization (FISH), and polymerase chain reaction (PCR) analysis and other studies for confirmation of a diagnosis of AML and to define whether participants have adverse, intermediate, or favorable AML risk features.
The enrolled trial population will be enriched for participants with adverse risk features by enrolling adverse, intermediate, and favorable risk participants at a ratio of 3:1:1, respectively (i.e., 72 adverse risk, 24 intermediate risk, and 24 favorable risk participants will be enrolled). Enrolled participants will then be randomized 2:1 to either the experimental arm or the active comparator arm.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Not specified
- Target Recruitment
- 26
Men and women ≥18 years old.
Must sign an informed consent form (ICF) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study.
Diagnosis of AML according to ICC 2022 (with the exclusion of MDS/AML with 10-19% blasts).
Previously untreated AML except may have received emergency leukapheresis, hydroxyurea, before study entry to control hyperleukocytosis.
Deemed unfit for intensive chemotherapy by meeting the criterial listed in the Protocol
Adequate liver and renal function, as per defined in the Protocol
Women of childbearing potential (WOCBP), defined as fertile women between menarche and post menopause unless permanently sterile, must have a negative highly sensitive serum β-human chorionic gonadotropin (β-hCG) or urine pregnancy test at screening
Must be willing to use contraception as consistent with institutional guidelines regarding the use of contraceptive methods for participants participating in clinical studies
Participants with HIV infection are eligible for the trial if the criteria included in the Protocol are met
Any prior treatment for AML (except those outlined in Inclusion Criterion #4)
History of prior HSCT (allogeneic or autologous transplants).
Active hepatitis B or C infection or other clinically active liver diseases as defined in the Protocol
Congestive heart failure severity that is New York Heart Association Class III or IV
Unstable angina
Known allergies, hypersensitivity, or intolerance to cusatuzumab, venetoclax, or azacitidine or their excipients (e.g., mannitol, an excipient of azacitidine)
Inability or difficulty swallowing capsules/tablets, malabsorption syndrome, or any disease or medical condition significantly affecting gastrointestinal function
Any condition for which, in the investigator’s opinion, participation would not be in the best interest of the participant (e.g., compromise the well-being) or physical limitations that could prevent, limit, or confound the protocol-specified assessments
Major surgery (e.g., requiring general anesthesia) ≤4 weeks prior to initiation of study treatment
Participant has received a HMA or venetoclax for MDS or myeloproliferative neoplasm
Leukemic involvement in the central nervous system
Participants with acute promyelocytic leukemia (APL)
ECOG performance status of 4 for participants 18 to 74 years of age and ECOG performance status of 3 or 4 for participants ≥75 years of age
Use of immune suppressive agents ≤4 weeks before the first administration of cusatuzumab. Participants may be included if free of systemic corticosteroids >5 days before the first administration of cusatuzumab with the exception of corticosteroids at physiologic replacement doses
Received a live, attenuated vaccine within 4 weeks prior to initiation of study drug
Active malignancies (i.e., progressing or requiring treatment change in the last 24 months), including advanced malignant hepatic tumors, other than the disease being treated under study. Exceptions listed in the protocol.
Any active systemic infection
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Overall survival (OS) Overall survival (OS)
- Secondary Outcome Measures
Name Time Method Complete remission (CR) rate defined as rate of complete remission per European Leukemia Network (ELN) 2022 Complete remission (CR) rate defined as rate of complete remission per European Leukemia Network (ELN) 2022
Event-free survival (EFS) per ELN 2022 Event-free survival (EFS) per ELN 2022
Composite CR (CRc) rate = the sum of rates for CR+CRh+CRi (CRh and CRi is defined as CR with partial hematologic recovery and incomplete hematologic recovery respectively) per ELN 2022 Composite CR (CRc) rate = the sum of rates for CR+CRh+CRi (CRh and CRi is defined as CR with partial hematologic recovery and incomplete hematologic recovery respectively) per ELN 2022
Rates of CRh, CRi, and MLFS Rates of CRh, CRi, and MLFS
Duration of complete remission defined as the time from first CR to hematological relapse or death from any cause Duration of complete remission defined as the time from first CR to hematological relapse or death from any cause
Time to first complete remission defined as time from randomization to first occurrence of CR Time to first complete remission defined as time from randomization to first occurrence of CR
Rate of measurable residual disease (MRD) negativity in participants achieving CR, CRh or CRi per ELN 2022 guidelines for MRD testing Rate of measurable residual disease (MRD) negativity in participants achieving CR, CRh or CRi per ELN 2022 guidelines for MRD testing
Proportion of participants proceeding to hematopoietic stem cell transplantation (HSCT) Proportion of participants proceeding to hematopoietic stem cell transplantation (HSCT)
OS in participants undergoing HSCT OS in participants undergoing HSCT
Adverse events (AEs) per NCI CTCAE criteria Adverse events (AEs) per NCI CTCAE criteria
Serious AEs (SAEs) and AEs leading to study drug discontinuation Serious AEs (SAEs) and AEs leading to study drug discontinuation
Incidence of dose modifications (interruptions/delays) due to AEs Incidence of dose modifications (interruptions/delays) due to AEs
Clinical laboratory tests, ECGs, physical examination findings, and vital signs Clinical laboratory tests, ECGs, physical examination findings, and vital signs
Serum concentration-time data and pharmacokinetic parameters as feasible for cusatuzumab Serum concentration-time data and pharmacokinetic parameters as feasible for cusatuzumab
Incidence of anti-cusatuzumab antibodies Incidence of anti-cusatuzumab antibodies
Incidence of neutralizing antibodies (NAb) Incidence of neutralizing antibodies (NAb)
OS and CR as well as other endpoints OS and CR as well as other endpoints
Rate of conversion from MRD negativity to MRD positivity in participants achieving CR, CRh or CRi Rate of conversion from MRD negativity to MRD positivity in participants achieving CR, CRh or CRi
Related Research Topics
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Trial Locations
- Locations (31)
Banner MD Anderson
🇺🇸Gilbert, Arizona, United States
City of Hope
🇺🇸Duarte, California, United States
University of California Los Angeles
🇺🇸Los Angeles, California, United States
University of Colorado Health - Anschutz Cancer Pavilion - Anschutz Medical Campus
🇺🇸Aurora, Colorado, United States
Yale School of Medicine
🇺🇸New Haven, Connecticut, United States
AdventHealth Medical Group Blood & Marrow Transplant at Orlando
🇺🇸Orlando, Florida, United States
The University of Iowa Hospitals & Clinics
🇺🇸Iowa City, Iowa, United States
University of Kentucky Chandler Medical Center
🇺🇸Lexington, Kentucky, United States
Norton Healthcare, Inc.
🇺🇸Louisville, Kentucky, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Scroll for more (21 remaining)Banner MD Anderson🇺🇸Gilbert, Arizona, United StatesAmy TolenadaContactAmy.Toleanada@bannerhealth.comRajneesh Nath, MDPrincipal Investigator