Back to resultsCusatuzumab in Combination With Background Therapy for the Treatment of Participants With Acute Myeloid Leukemia (ELEVATE)
Primary Purpose
Leukemia, Myeloid, Acute
Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Cusatuzumab
Azacitidine
Venetoclax
Sponsored by
About this trial
This is an interventional treatment trial for Leukemia, Myeloid, Acute
Eligibility Criteria
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)
Sites / Locations
- City of Hope
- Norton Cancer Institute
- Barbara Ann Karmanos Cancer Institute
- Roswell Park Cancer Institute
- Weill Cornell Medicine
- Memorial Sloan Kettering Cancer Center
- University of Rochester
- University of Pittsburgh School of Medicine
- The University of Texas MD Anderson Cancer Center
- University of Vermont
- Wisconsin Medical Center
- Tom Baker Cancer Centre
- University of Alberta Hospital
- University of Toronto
- McGill University Health Centre
- Universitaetsklinik Hamburg-Eppendorf
- Universitaetsklinikum Leipzig
- Klinikum der Universitaet Muenchen
- Szpital Uniwersytecki w Krakowie
- Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi
- Instytut Hematologii i Transfuzjologii
- INSELSPITAL, Universitätsspital Bern
- Kantonsspital St.Gallen
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Experimental: Cohort 2: Cusatuzumab + Venetoclax
Cohort 3: Cusatuzumab + Venetoclax + Azacitidine (CVA)
Arm Description
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.
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).
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Serum Concentration of Cusatuzumab
Serum concentration of cusatuzumab will be assessed.
Number of Participants with Anti-cusatuzumab Antibodies
Number of participants with anti-drug antibodies to cusatuzumab will be reported.
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.
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.
Percentage of Participants with CR with Incomplete Recovery (CRi)
Percentage of participants with CRi will be reported based on ELN 2017 response criteria assessment.
Percentage of Participants with CR plus CRh
Percentage of participants with CR plus CRh will be reported based on ELN 2017 response criteria assessment.
Overall Response Rate (ORR)
ORR is defined as percentage of participants with CR, CRh and CRi based on ELN 2017 response criteria assessment.
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).
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).
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.
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.
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.
Full Information
NCT ID
NCT04150887
First Posted
November 1, 2019
Last Updated
August 7, 2023
Sponsor
OncoVerity, Inc.
Collaborators
argenx, Janssen Research & Development, LLC
1. Study Identification
Unique Protocol Identification Number
NCT04150887
Brief Title
Cusatuzumab in Combination With Background Therapy for the Treatment of Participants With Acute Myeloid Leukemia
Acronym
ELEVATE
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 23, 2019 (Actual)
Primary Completion Date
May 15, 2024 (Anticipated)
Study Completion Date
May 15, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
OncoVerity, Inc.
Collaborators
argenx, Janssen Research & Development, LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Myeloid, Acute
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
61 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Experimental: Cohort 2: Cusatuzumab + Venetoclax
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 3: Cusatuzumab + Venetoclax + Azacitidine (CVA)
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Cusatuzumab
Other Intervention Name(s)
JNJ-74494550, ARGX-110
Intervention Description
Cusatuzumab will be administered as a dose of 10mg/kg or 20mg/kg intravenously.
Intervention Type
Drug
Intervention Name(s)
Azacitidine
Other Intervention Name(s)
Vidaza
Intervention Description
Azacitidine will be administered 75 mg/m^2 subcutaneously or intravenously.
Intervention Type
Drug
Intervention Name(s)
Venetoclax
Other Intervention Name(s)
Venclexta
Intervention Description
Venetoclax will be administered orally and the dose will ramp-up to 400 mg.
Primary Outcome Measure Information:
Title
Frequency and Severity of Adverse Events (AEs), Laboratory Abnormalities, and Physical Exam Findings as a Measure of Safety
Description
Frequency and severity of AEs, laboratory abnormalities, and physical exam findings will be reported.
Time Frame
Up to 42 months
Secondary Outcome Measure Information:
Title
Serum Concentration of Cusatuzumab
Description
Serum concentration of cusatuzumab will be assessed.
Time Frame
Up to 23 months
Title
Number of Participants with Anti-cusatuzumab Antibodies
Description
Number of participants with anti-drug antibodies to cusatuzumab will be reported.
Time Frame
Up to 23 months
Title
Percentage of Participants with Complete Response (CR)
Description
Percentage of participants with complete response based on European Leukemia Network (ELN) 2017 response criteria assessment will be reported.
Time Frame
Up to 42 months
Title
Percentage of Participants with Complete Remission with Partial Hematological Recovery (CRh)
Description
Percentage of participants with CRh will be reported based on ELN 2017 response criteria assessment.
Time Frame
Up to 42 months
Title
Percentage of Participants with CR with Incomplete Recovery (CRi)
Description
Percentage of participants with CRi will be reported based on ELN 2017 response criteria assessment.
Time Frame
Up to 42 months
Title
Percentage of Participants with CR plus CRh
Description
Percentage of participants with CR plus CRh will be reported based on ELN 2017 response criteria assessment.
Time Frame
Up to 42 months
Title
Overall Response Rate (ORR)
Description
ORR is defined as percentage of participants with CR, CRh and CRi based on ELN 2017 response criteria assessment.
Time Frame
Up to 42 months
Title
Percentage of Participants with CR without MRD
Description
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).
Time Frame
Up to 42 months
Title
Percentage of Participants with Negative MRD who Achieved CR, CRh, CRi, or Morphologic Leukemia-free State (MLFS)
Description
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).
Time Frame
Up to 42 months
Title
Cohort 2 and 3: Time to Response
Description
Time to response is defined as time from first dose to achieving the first response of CR, CRh, or CRi.
Time Frame
Up to 42 months
Title
Cohort 2 and 3: Duration of Response
Description
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.
Time Frame
Up to 42 months
Title
Cohort 2 and 3: Red Blood Cell (RBC) or Platelet Transfusion Independence
Description
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.
Time Frame
Up to 42 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clayton Smith, MD
Organizational Affiliation
OncoVerity, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Norton Cancer Institute
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40207
Country
United States
Facility Name
Barbara Ann Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14203
Country
United States
Facility Name
Weill Cornell Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
University of Rochester
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
University of Pittsburgh School of Medicine
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
The University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Vermont
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05401
Country
United States
Facility Name
Wisconsin Medical Center
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Tom Baker Cancer Centre
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N2
Country
Canada
Facility Name
University of Alberta Hospital
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2B7
Country
Canada
Facility Name
University of Toronto
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
McGill University Health Centre
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H4A 3J1
Country
Canada
Facility Name
Universitaetsklinik Hamburg-Eppendorf
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Universitaetsklinikum Leipzig
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
Klinikum der Universitaet Muenchen
City
München
ZIP/Postal Code
81377
Country
Germany
Facility Name
Szpital Uniwersytecki w Krakowie
City
Krakow
ZIP/Postal Code
31-501
Country
Poland
Facility Name
Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi
City
Lodz
ZIP/Postal Code
93-513
Country
Poland
Facility Name
Instytut Hematologii i Transfuzjologii
City
Warszawa
ZIP/Postal Code
02-776
Country
Poland
Facility Name
INSELSPITAL, Universitätsspital Bern
City
Bern
ZIP/Postal Code
3010
Country
Switzerland
Facility Name
Kantonsspital St.Gallen
City
St. Gallen
ZIP/Postal Code
9007
Country
Switzerland
12. IPD Sharing Statement
Plan to Share IPD
Yes
Learn more about this trial
Cusatuzumab in Combination With Background Therapy for the Treatment of Participants With Acute Myeloid Leukemia
We'll reach out to this number within 24 hrs