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

An Open-label, Multicenter, Phase 1b Study of OV-1001 (Cusatuzumab; Anti-CD70 Monoclonal Antibody) in Combination With Background Therapy for the Treatment of Subjects With Acute Myeloid Leukemia

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Leukemia, Myeloid, Acute
• Intervention / Treatment: Drug: Cusatuzumab; Drug: Venetoclax; Drug: Azacitidine

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta Hospital
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • University of Toronto
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre
• Germany
  • Hamburg, Germany, 20246
    • Universitaetsklinik Hamburg-Eppendorf
  • Leipzig, Germany, 04103
    • Universitaetsklinikum Leipzig
  • München, Germany, 81377
    • Klinikum der Universitaet Muenchen
• Poland
  • Krakow, Poland, 31-501
    • Szpital Uniwersytecki w Krakowie
  • Lodz, Poland, 93-513
    • Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi
  • Warszawa, Poland, 02-776
    • Instytut Hematologii i Transfuzjologii
• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital, Universitätsspital Bern
  • St. Gallen, Switzerland, 9007
    • Kantonsspital St.Gallen
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Norton Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer Institute
  • New York
    • Buffalo, New York, United States, 14203
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10021
      • Weill Cornell Medicine
    • Rochester, New York, United States, 14642
      • University of Rochester
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh School of Medicine
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Wisconsin Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: Cohort 2: Cusatuzumab + Venetoclax; 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; Cusatuzumab will be administered as a dose of 10mg/kg or 20mg/kg intravenously.; Other Names: ARGX-110; JNJ-74494550; Drug: Venetoclax; Venetoclax will be administered orally and the dose will ramp-up to 400 mg.; Other Names: Venclexta
Experimental: Cohort 3: Cusatuzumab + Venetoclax + Azacitidine (CVA); 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; Cusatuzumab will be administered as a dose of 10mg/kg or 20mg/kg intravenously.; Other Names: ARGX-110; JNJ-74494550; Drug: Venetoclax; Venetoclax will be administered orally and the dose will ramp-up to 400 mg.; Other Names: Venclexta; Drug: Azacitidine; Azacitidine will be administered 75 mg/m^2 subcutaneously or intravenously.; Other Names: Vidaza

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Concentration of Cusatuzumab	Serum concentration of cusatuzumab will be assessed.	Up to 23 months
Number of Participants with Anti-cusatuzumab Antibodies	Number of participants with anti-drug antibodies to cusatuzumab will be reported.	Up to 23 months
Percentage of Participants with Complete Response (CR)	Percentage of participants with complete response based on European Leukemia Network (ELN) 2017 response criteria assessment will be reported.	Up to 42 months
Percentage of Participants with Complete Remission with Partial Hematological Recovery (CRh)	Percentage of participants with CRh will be reported based on ELN 2017 response criteria assessment.	Up to 42 months
Percentage of Participants with CR with Incomplete Recovery (CRi)	Percentage of participants with CRi will be reported based on ELN 2017 response criteria assessment.	Up to 42 months
Percentage of Participants with CR plus CRh	Percentage of participants with CR plus CRh will be reported based on ELN 2017 response criteria assessment.	Up to 42 months
Overall Response Rate (ORR)	ORR is defined as percentage of participants with CR, CRh and CRi based on ELN 2017 response criteria assessment.	Up to 42 months
Percentage of Participants with CR without MRD	Percentage of participants with CR without minimal residual disease (MRD) will be reported and is defined as less than (<) 1 blast or leukemic stem cell in 1,000 leukocytes (MRD level <10^-3).	Up to 42 months
Percentage of Participants with Negative MRD who Achieved CR, CRh, CRi, or Morphologic Leukemia-free State (MLFS)	Percentage of participants with negative MRD who achieved CR, CRh, CRi, or MLFS will be reported and is defined as < 1 blast or leukemic stem cell in 1,000 leukocytes (MRD level <10^-3).	Up to 42 months
Cohort 2 and 3: Time to Response	Time to response is defined as time from first dose to achieving the first response of CR, CRh, or CRi.	Up to 42 months
Cohort 2 and 3: Duration of Response	Duration of response is defined as time from achieving the first response of CR, CRh, or CRi to hematologic relapse or death of any cause.	Up to 42 months
Cohort 2 and 3: Red Blood Cell (RBC) or Platelet Transfusion Independence	Transfusion independence (RBC or platelets) is defined as a period of greater than or equal to (>=) 56 consecutive days with no transfusion between first dose of study drug and the last dose of study drug +30 days.	Up to 42 months

Collaborators and Investigators

• Sponsor: OncoVerity, Inc.
• Collaborators: Janssen Research & Development, LLC; argenx
• Investigators: Study Director: Clayton Smith, MD, OncoVerity, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 23, 2019
• Primary Completion (Estimated): May 15, 2024
• Study Completion (Estimated): May 15, 2024

Study Registration Dates

• First Submitted: November 1, 2019
• First Submitted That Met QC Criteria: November 1, 2019
• First Posted (Actual): November 5, 2019

Study Record Updates

• Last Update Posted (Actual): August 9, 2023
• Last Update Submitted That Met QC Criteria: August 7, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Venetoclax; Azacitidine
• Other Study ID Numbers: ELEV20235 (Other Identifier: OncoVerity, Inc.); 2019-002808-41 (EudraCT Number); 74494550AML1003 (Other Identifier: Janssen Research & Development, LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Plan Description:

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency.

As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No