Cusatuzumab in Combination With Background Therapy for the Treatment of Participants With Acute Myeloid Leukemia

NCT04150887 | Active Not Recruiting Phase 1 FDA Drug

• 3 other identifiers: ELEV202352019-002808-4174494550AML1003
• Study Type: interventional
• Target: 61
• Locations: 5 countries
• Sites: 23

Brief Summary

The purpose of the study is to characterize safety and tolerability of cusatuzumab in combination with various therapies used to treat acute myeloid leukemia (AML).

Conditions

Leukemia, Myeloid, Acute

Outcome Measures

Primary Outcomes (1)

• Frequency and Severity of Adverse Events (AEs), Laboratory Abnormalities, and Physical Exam Findings as a Measure of Safety

  Frequency and severity of AEs, laboratory abnormalities, and physical exam findings will be reported.

  Up to 42 months

Secondary Outcomes (12)

• Serum Concentration of Cusatuzumab

  Up to 23 months

• Number of Participants with Anti-cusatuzumab Antibodies

  Up to 23 months

• Percentage of Participants with Complete Response (CR)

  Up to 42 months

• Percentage of Participants with Complete Remission with Partial Hematological Recovery (CRh)

  Up to 42 months

• Percentage of Participants with CR with Incomplete Recovery (CRi)

  Up to 42 months

Study Arms (2)

Experimental: Cohort 2: Cusatuzumab + Venetoclax

EXPERIMENTAL

Participants enrolled in this cohort will receive venetoclax ramp-up to 400 mg orally (as background therapy) starting on Cycle 1 Day 1 and followed by 400 mg daily dosing starting on Cycle 1 Day 4 plus cusatuzumab IV on Day 3 and Day 17 of each 28-day cycle. Cohort 2 will not be enrolled in the US.

Drug: Cusatuzumab; Drug: Venetoclax

Cohort 3: Cusatuzumab + Venetoclax + Azacitidine (CVA)

EXPERIMENTAL

Participants enrolled at US sites will receive cusatuzumab 10 mg/kg and potentially escalate to 20 mg/kg IV in combination with azacitidine 75 mg/m\^2 SC or IV plus venetoclax ramp-up to 400 mg orally (as background therapies). Participants enrolled from ex-US sites will receive cusatuzumab 20 mg/kg and potentially de-escalate to 10 mg/kg IV in combination with azacitidine 75 mg/m\^2 SC or IV plus venetoclax ramp-up to 400 mg orally (as background therapies).

Drug: Cusatuzumab; Drug: Azacitidine; Drug: Venetoclax

Interventions

Cusatuzumab DRUG

Cusatuzumab will be administered as a dose of 10mg/kg or 20mg/kg intravenously.

Also known as: JNJ-74494550, ARGX-110

Cohort 3: Cusatuzumab + Venetoclax + Azacitidine (CVA); Experimental: Cohort 2: Cusatuzumab + Venetoclax

Azacitidine DRUG

Azacitidine will be administered 75 mg/m\^2 subcutaneously or intravenously.

Also known as: Vidaza

Cohort 3: Cusatuzumab + Venetoclax + Azacitidine (CVA)

Venetoclax DRUG

Venetoclax will be administered orally and the dose will ramp-up to 400 mg.

Also known as: Venclexta

Cohort 3: Cusatuzumab + Venetoclax + Azacitidine (CVA); Experimental: Cohort 2: Cusatuzumab + Venetoclax

Eligibility Criteria

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

You may qualify if:

• Diagnosis of acute myeloid leukemia (AML) according to World Health Organization 2016 criteria . Participants with acute promyelocytic leukemia (APL) are not eligible
• Must be ineligible for intensive chemotherapy
• De novo or secondary AML
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Previously untreated AML except: emergency leukapheresis, hydroxyurea, and/or 1 dose 1-2 gram per meter square (g/m\^2) cytarabine during the Screening Phase to control hyperleukocytosis. These treatments must be discontinued greater than or equal to (\>=) 24 hours prior to start of study drug. Empiric all trans retinoic acid (ATRA) treatment for presumed acute promyelocytic leukemia (APL) is permitted but APL must be ruled out and ATRA must be discontinued \>=24 hours prior to the start of study drug
• Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies

You may not qualify if:

• Leukemic involvement of the central nervous system
• Eligible for an allogeneic hematopoietic stem cell transplantation at study entry
• Received a live, attenuated vaccine within 4 weeks prior to initiation of study drug
• A history of human immunodeficiency virus (HIV) antibody positive or tests positive for HIV if tested at screening
• Known allergies, hypersensitivity, or intolerance to cusatuzumab, venetoclax, azacitidine, or their excipients (example: mannitol, an excipient of azacitidine)

Sponsors & Collaborators

• OncoVerity, Inc.: lead
• argenx: collaborator
• Janssen Research & Development, LLC: collaborator

Study Sites (23)

City of Hope

Duarte, California, 91010, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40207, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14203, United States

Location

Weill Cornell Medicine

New York, New York, 10021, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

University of Pittsburgh School of Medicine

Pittsburgh, Pennsylvania, 15232, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Vermont

Burlington, Vermont, 05401, United States

Location

Wisconsin Medical Center

Milwaukee, Wisconsin, 53226, United States

Location

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

University of Alberta Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

University of Toronto

Toronto, Ontario, M5G 2M9, Canada

Location

McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada

Location

Universitaetsklinik Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Universitaetsklinikum Leipzig

Leipzig, 04103, Germany

Location

Klinikum der Universitaet Muenchen

München, 81377, Germany

Location

Szpital Uniwersytecki w Krakowie

Krakow, 31-501, Poland

Location

Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi

Lodz, 93-513, Poland

Location

Instytut Hematologii i Transfuzjologii

Warsaw, 02-776, Poland

Location

INSELSPITAL, Universitätsspital Bern

Bern, 3010, Switzerland

Location

Kantonsspital St.Gallen

Sankt Gallen, 9007, Switzerland

Location

Related Publications (2)

• Pabst T, Papayannidis C, Demirkan F, Doronin V, Fogliatto LM, Guttke C, Gyan E, Hamad N, Herrera P, Hultberg A, Jacobs J, Johnson AJ, Langlois A, Ma X, Martinelli G, Arnan M, Muller R, Nottage K, Ofran Y, Ozcan M, Samoilova O, Tolbert JA, Trudel GC, Xiu L, Vey N, Wei AH. Cusatuzumab plus azacitidine in newly diagnosed acute myeloid leukaemia ineligible for intensive chemotherapy (CULMINATE): part one of a randomised, phase 2, dose optimisation study. Lancet Haematol. 2023 Nov;10(11):e902-e912. doi: 10.1016/S2352-3026(23)00207-7.

  PMID: 37914483 DERIVED

• Dewulf J, Flieswasser T, Delahaye T, Vangestel C, Miranda A, de Haard H, Jacobs J, Smits E, Van den Wyngaert T, Elvas F. Site-specific 68Ga-labeled nanobody for PET imaging of CD70 expression in preclinical tumor models. EJNMMI Radiopharm Chem. 2023 Apr 24;8(1):8. doi: 10.1186/s41181-023-00194-3.

  PMID: 37093350 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Azacitidine; venetoclax

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

Study Officials

• Clayton Smith, MD

  OncoVerity, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2019
• First Posted: November 5, 2019
• Study Start: December 23, 2019
• Primary Completion (Estimated): May 15, 2026
• Study Completion (Estimated): May 15, 2026
• Last Updated: April 17, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share

Locations

PL (3); CH (2); US (11); CA (4); DE (3)