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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

Phase 2
Recruiting
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
Inclusion Criteria

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

Exclusion Criteria

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
NameTimeMethod
Overall survival (OS)

Overall survival (OS)

Secondary Outcome Measures
NameTimeMethod
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

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 States
Amy Tolenada
Contact
Amy.Toleanada@bannerhealth.com
Rajneesh Nath, MD
Principal Investigator

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