A Study Comparing Venetoclax and Azacitidine Plus Cusatuzumab to Venetoclax and Azacitidine in Newly Diagnosed AML Ineligible for Intensive Therapy

NCT06384261 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: OV-AML-1231
• Study Type: interventional
• Target: 120
• Locations: 4 countries
• Sites: 31

Brief Summary

The goal of this clinical trial is to learn if participants treated with the experimental drug cusatuzumab added to venetoclax and azacitidine works to treat acute myeloid leukemia (AML) compared to venetoclax and azacitidine. Venetoclax and azacitidine are drugs commonly used to treat AML in patients that are unable to receive chemotherapy to treat AML. The main question the clinical trial aims to answer is does cusatuzumab added to venetoclax and azacitidine prolong the length of time participants live compared to venetoclax and azacitidine?

Conditions

Leukemia, Myeloid, Acute

Outcome Measures

Primary Outcomes (1)

• Overall survival

  In all randomized participants

  From date of randomization until the date of death from any cause, assessed up to 5 years

Secondary Outcomes (15)

• Complete Remission rate (CR)

  From date of randomization to relapse or criteria for refractory disease are met, assessed up to 3 years

• Event-free survival (EFS)

  From date of randomization to date of treatment failure, hematologic relapse from CR/CRh/CRi or death from any cause, assessed up to 5 years

• Composite CR rate (CRc)

  From date of randomization to relapse or criteria for refractory disease are met, assessed up to 3 years

• Rate of CRh and CRi

  From date of randomization to relapse or criteria for refractory disease are met, assessed up to 3 years

• Duration of CR

  From date of first CR to hematological relapse or death from any cause, assessed up to 5 years

Study Arms (2)

Cusatuzumab in combination with venetoclax and azacitidine

EXPERIMENTAL

Cusatuzumab 20 mg/kg administered intravenously on days 3 and 17 in combination with venetoclax administered orally up to 400 mg once daily and azacitidine 75 mg/m\^2 administered subcutaneously or intravenously once daily for 7 days of a 28 day cycle

Drug: Cusatuzumab; Drug: Venetoclax; Drug: Azacitidine

Venetoclax in combination with azacitidine

ACTIVE COMPARATOR

Venetoclax administered orally up to 400 mg once daily and azacitidine 75 mg/m\^2 administered subcutaneously or intravenously once daily for 7 days of a 28 day cycle

Drug: Venetoclax; Drug: Azacitidine

Interventions

Cusatuzumab DRUG

CD70 monoclonal antibody

Also known as: OV-1001

Cusatuzumab in combination with venetoclax and azacitidine

Venetoclax DRUG

BCL-2 inhibitor

Cusatuzumab in combination with venetoclax and azacitidine; Venetoclax in combination with azacitidine

Azacitidine DRUG

Hypomethylating agent

Cusatuzumab in combination with venetoclax and azacitidine; Venetoclax in combination with azacitidine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Previously untreated AML except may have received emergency leukapheresis, hydroxyurea before study entry to control hyperleukocytosis
• Deemed unfit for intensive chemotherapy by meeting at least 1 of the following criteria:
• Participant is ≥75 years of age with Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 OR
• Participant is ≥18 to 74 years of age and has any of the following comorbidities:
• ECOG performance status of 2 or 3
• Cardiac status including any one of the following: congestive heart failure requiring treatment or ejection fraction ≤50% or chronic stable angina
• Known history of diffusion capacity of lung for carbon monoxide (DLCO) ≤65% of forced expiratory volume in the first second (FEV1) ≤65%
• Creatinine clearance (CrCl) ≥15 mL/min to \<45 mL/min
• Hepatic disorder with total bilirubin \>1.5 to 3x the upper limit of normal (ULN)
• Any other comorbidity that the investigators determine to be incompatible with conventional intensive chemotherapy
• Adequate liver and renal function defined as:
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<3xULN; for participants with leukemic infiltration of the liver (documented by biopsy or imaging), AST and ALT \<5xULN is permitted
• Total bilirubin ≤1.5xULN, unless bilirubin rise is due to Gilbert's syndrome or of nonhepatic origin. Participants who are \<75 years of age may have a bilirubin up to 3xULN.

You may not qualify if:

• Participant has received a hypomethylating agent (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
• Nonmelanoma skin cancer treated within the last 24 months that is considered completely cured
• Adequately treated breast lobular carcinoma in situ and breast ductal carcinoma in situ
• Adequately treated cervical carcinoma in situ and breast ductal carcinoma in situ
• History of localized breast cancer and receiving anti-hormonal agents, or history of localized prostate cancer (N0M0) and receiving androgen depravation therapy
• A malignancy that is considered cured with minimal risk of recurrence
• Any active systemic infection
• History of prior HSCT (allogeneic or autologous transplants)
• Active hepatitis B or C infection or other clinically active liver diseases ad defined below:
• Seropositivity for hepatitis B is defined by a positive test for hepatitis B surface antigen (HBsAg)

Sponsors & Collaborators

• OncoVerity, Inc.: lead

Study Sites (31)

Banner MD Anderson

Gilbert, Arizona, 85234, United States

RECRUITING

City of Hope

Duarte, California, 91010, United States

RECRUITING

University of California Los Angeles

Los Angeles, California, 90095, United States

RECRUITING

University of Colorado Health - Anschutz Cancer Pavilion - Anschutz Medical Campus

Aurora, Colorado, 80045, United States

RECRUITING

Yale School of Medicine

New Haven, Connecticut, 06510, United States

RECRUITING

AdventHealth Medical Group Blood &amp; Marrow Transplant at Orlando

Orlando, Florida, 32804, United States

RECRUITING

The University of Iowa Hospitals & Clinics

Iowa City, Iowa, 52242, United States

RECRUITING

University of Kentucky Chandler Medical Center

Lexington, Kentucky, 40536, United States

RECRUITING

Norton Healthcare, Inc.

Louisville, Kentucky, 40202, United States

RECRUITING

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

NOT YET RECRUITING

Hofstra/Northwell Health

Lake Success, New York, 11042, United States

RECRUITING

Cornell University

New York, New York, 10065, United States

RECRUITING

University of Rochester Medical Center

Rochester, New York, 14642, United States

RECRUITING

Wake Forest North Carolina

Winston-Salem, North Carolina, 27157, United States

NOT YET RECRUITING

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

RECRUITING

Fred Hutch Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

RECRUITING

Medical College of Wisonsin

Milwaukee, Wisconsin, 53226, United States

NOT YET RECRUITING

Tom Baker Cancer Center-Alberta Health Services - University of Calgary

Calgary, Alberta, T2N 4N2, Canada

RECRUITING

Stollery Children's Hospital-Walter C Mackenzie Health Sciences Centre - University of Alberta

Edmonton, Alberta, T6G 2B7, Canada

RECRUITING

Vancouver General Hospital, Gordon and Leslie Diamond Health Care Centre

Vancouver, British Columbia, V5Z 1M9, Canada

RECRUITING

University of Western Ontario

London, Ontario, N6A5W9, Canada

RECRUITING

The Ottawa Hospital - General Campus

Ottawa, Ontario, K1H8L6, Canada

RECRUITING

Princess Margaret Cancer Centre

Toronto, Ontario, M5F 2M9, Canada

RECRUITING

Saskatchewan Cancer Agency - Saskatoon Cancer Centre

Saskatoon, Saskatchewan, S7N4H4, Canada

RECRUITING

Marien Hospital Duesseldorf

Düsseldorf, 40479, Germany

RECRUITING

Universitaetsklinik Frankfurt

Frankfurt, 60560, Germany

RECRUITING

Medizinische Hochschule Hanover, Hannover Medical School

Hanover, 30625, Germany

RECRUITING

Universitaetsklinik um Schleswig-Holstein, UKSH-Campus Kiel

Kiel, 24105, Germany

RECRUITING

Inselspital Bern

Bern, 3010, Switzerland

RECRUITING

HFR Fribourg - Hopital Cantonal

Fribourg, Switzerland, Switzerland

RECRUITING

Kantonsspital St. Gallen

Sankt Gallen, 9007, Switzerland

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

venetoclax; Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Central Study Contacts

OncoVerity OncoVerity

CONTACT

8002201674; helpdesk@oncoverity.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2024
• First Posted: April 25, 2024
• Study Start: July 22, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: September 10, 2025

Record last verified: 2025-09

Locations

DE (4); US (17); CA (7); CH (3)