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A Study of Cusatuzumab Plus Azacitidine in Japanese Participants With Newly Diagnosed Acute Myeloid Leukemia or High-risk Myelodysplastic Syndrome Who Are Not Candidates for Intensive Treatment

Primary Purpose

Leukemia, Myeloid, Acute

Status

Completed

Phase

Phase 1

Locations

Japan

Study Type

Interventional

Intervention

Cusatuzumab

Azacitidine

About this trial

This is an interventional treatment trial for Leukemia, Myeloid, Acute

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

For acute myeloid leukemia (AML) participants: AML according to World Health Organization (WHO) 2016 criteria and fulfilling all of the following criteria:(a) more than or equal to (>=) 75 years of age, or younger participants who are not eligible for or not willing to receive an intensive treatment (including stem cell transplantation) with curative intent and (b) previously untreated AML (except: emergency leukapheresis, low dose of cytarabine and/or hydroxyurea during the screening phase to control hyperleukocytosis but must be discontinued at least one day prior to start of cusatuzumab [Part 1] or azacitidine [Part 2]). All trans retinoic acid (ATRA) treatment for presumed acute promyelocytic leukemia (APL) is permitted but must be discontinued at least 1 day prior to the start of cusatuzumab (Part 1) or azacitidine (Part 2)
For Myelodysplastic Syndrome (MDS) participants (only for Part 2): MDS according to WHO 2016 criteria and fulfilling all of the following criteria: (a) Not eligible for or not willing to receive allogenic stem cell transplantation,(b) very high or high-risk MDS according to Revised International Prognostic Scoring System (IPSS-R) and (c) previously untreated MDS (except: transfusion and/or cytokine therapy including erythropoietin)
Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2
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
A woman of childbearing potential must have a negative highly sensitive serum (beta human chorionic gonadotropin [beta hCG]) or urine pregnancy at screening

Exclusion Criteria:

Acute promyelocytic leukemia (APL) with t (15;17), or its molecular equivalent promyelocytic leukemia retinoic acid receptor (PML RAR alpha)
Leukemic involvement or clinical symptoms of leukemic involvement of the central nervous system
Known allergies, hypersensitivity, or intolerance to cusatuzumab or azacitidine or its excipients (example, mannitol, an excipient of azacitidine)
Prior treatment with a hypomethylating agent for treatment of AML or MDS
A diagnosis of other malignancy that requires concurrent nonsurgical treatment

Sites / Locations

Fukushima Medical University Hospital
Gunmaken Saiseikai Maebashi Hospital
Osaka City General Hospital
NTT Medical Center Tokyo
University of Fukui Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Part 1 (Dose Finding): Cusatuzumab + Azacitidine

Part 2 (Dose Expansion): Cusatuzumab + Azacitidine

Arm Description

Participants with acute myeloid leukemia (AML) will receive cusatuzumab intravenously (IV) in combination with azacitidine subcutaneously (SC) or IV. The dose levels will be escalated based on the decisions of the Study Evaluation Team (SET) until the recommended Phase 2 Dose (RP2D) has been identified.

Participants with acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS) will receive cusatuzumab intravenously (IV) at the recommended Phase 2 dose (RP2D) determined in Part 1 in combination with azacitidine subcutaneously (SC) or IV.

Outcomes

Primary Outcome Measures

Part 1 and Part 2: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

Number of participants with AEs and SAEs will be reported.

Part 1 and Part 2: Number of Participants with Dose-Limiting Toxicity (DLTs)

Number of participants with DLTs will be reported.

Part 1 and Part 2: Severity of DLT as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)

Severity of DLT as assessed by NCI-CTCAE in participants will be reported.

Secondary Outcome Measures

Part 1 and Part 2: Percentage of Participants with Complete Response (CR)

Percentage of participants with complete response based on response criteria per investigator assessment in participants with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) will be reported.

Part 1: Objective Response Rate (ORR)

ORR is defined as percentage of participants with CR, CRh and CRi based on response criteria per investigator assessment in participants with AML.

Part 2: Objective Response Rate (ORR)

ORR is defined as the percentage of participants with CR, partial response (PR) and marrow CR based on response criteria per investigator assessment in participants with MDS.

Part 2: Percentage of Participants with Hematologic Improvement (HI)

Percentage of participants with hematologic improvement will be reported according to response criteria per investigator assessment in participants with MDS.

Part 1 and Part 2: Time to Response

Time to response is defined as time from first dose to achieving the first response of CR, CRh, or CRi in participants with AML and CR, PR or marrow CR in participants with MDS..

Part 1 and Part 2: Duration of Response

Duration of response is defined as time from achieving the first response of CR, CRh, or CRi in participants with AML and CR, PR or marrow CR in participants with MDS to hematologic relapse or death of any cause.

Part 1 and Part 2: Red Blood Cell (RBC) or Platelets Transfusion Independence

Transfusion independence (RBC or platelets) is defined as a period of at least 56 consecutive days with no transfusion between first dose of study drug and the last dose of study drug +30 days.

Part 1 and Part 2: Overall Survival (OS)

OS is defined as the time from initial study intervention administration to death from any cause.

Part 1 and Part 2: Maximum Serum Concentration (Cmax) of Cusatuzumab

Cmax is the maximum observed serum concentration.

Part 1 and Part 2: Serum Trough Concentration (Ctrough) of Cusatuzumab

Ctrough is the serum concentration immediately prior to the next drug administration.

Full Information

NCT ID

NCT04241549

First Posted

January 23, 2020

Last Updated

August 7, 2023

Sponsor

OncoVerity, Inc.

Collaborators

argenx, Janssen Pharmaceutical K.K.

1. Study Identification

Unique Protocol Identification Number

NCT04241549

Brief Title

A Study of Cusatuzumab Plus Azacitidine in Japanese Participants With Newly Diagnosed Acute Myeloid Leukemia or High-risk Myelodysplastic Syndrome Who Are Not Candidates for Intensive Treatment

Official Title

A Phase 1 Study of Cusatuzumab Plus Azacitidine in Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia or High-risk Myelodysplastic Syndrome Who Are Not Candidates for Intensive Treatment

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Completed

Study Start Date

March 25, 2020 (Actual)

Primary Completion Date

July 19, 2021 (Actual)

Study Completion Date

July 19, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

OncoVerity, Inc.

Collaborators

argenx, Janssen Pharmaceutical K.K.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study is to determine the recommended Phase 2 dose and evaluate safety profile of cusatuzumab in combination with azacitidine in Japanese participants with treatment naïve acute myeloid leukemia (AML) who are not candidates for intensive treatment.

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

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

6 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part 1 (Dose Finding): Cusatuzumab + Azacitidine

Arm Type

Experimental

Arm Description

Arm Title

Part 2 (Dose Expansion): Cusatuzumab + Azacitidine

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Cusatuzumab

Other Intervention Name(s)

JNJ-74494550, ARGX-110

Intervention Description

Cusatuzumab at a dose 20 milligram per kilogram (mg/kg) once every 2 weeks will be administered intravenously.

Intervention Type

Drug

Intervention Name(s)

Azacitidine

Other Intervention Name(s)

VIDAZA

Intervention Description

Azacitidine at a dose 75 milligram per square meters (mg/m^2) will be administered subcutaneously or intravenously.

Primary Outcome Measure Information:

Title

Part 1 and Part 2: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

Description

Number of participants with AEs and SAEs will be reported.

Time Frame

Up to 3 years

Title

Part 1 and Part 2: Number of Participants with Dose-Limiting Toxicity (DLTs)

Description

Number of participants with DLTs will be reported.

Time Frame

Up to 42 days

Title

Part 1 and Part 2: Severity of DLT as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)

Description

Severity of DLT as assessed by NCI-CTCAE in participants will be reported.

Time Frame

Up to 42 days

Secondary Outcome Measure Information:

Title

Part 1 and Part 2: Percentage of Participants with Complete Response (CR)

Description

Time Frame

Up to 9 months

Title

Part 1: Objective Response Rate (ORR)

Description

ORR is defined as percentage of participants with CR, CRh and CRi based on response criteria per investigator assessment in participants with AML.

Time Frame

Up to 6 months

Title

Part 2: Objective Response Rate (ORR)

Description

ORR is defined as the percentage of participants with CR, partial response (PR) and marrow CR based on response criteria per investigator assessment in participants with MDS.

Time Frame

Up to 9 months

Title

Part 2: Percentage of Participants with Hematologic Improvement (HI)

Description

Percentage of participants with hematologic improvement will be reported according to response criteria per investigator assessment in participants with MDS.

Time Frame

Up to 9 months

Title

Part 1 and Part 2: Time to Response

Description

Time to response is defined as time from first dose to achieving the first response of CR, CRh, or CRi in participants with AML and CR, PR or marrow CR in participants with MDS..

Time Frame

Up to 3 years

Title

Part 1 and Part 2: Duration of Response

Description

Time Frame

Up to 3 years

Title

Part 1 and Part 2: Red Blood Cell (RBC) or Platelets Transfusion Independence

Description

Transfusion independence (RBC or platelets) is defined as a period of at least 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 3 years

Title

Part 1 and Part 2: Overall Survival (OS)

Description

OS is defined as the time from initial study intervention administration to death from any cause.

Time Frame

Up to 3 years

Title

Part 1 and Part 2: Maximum Serum Concentration (Cmax) of Cusatuzumab

Description

Cmax is the maximum observed serum concentration.

Time Frame

Up to 3 years

Title

Part 1 and Part 2: Serum Trough Concentration (Ctrough) of Cusatuzumab

Description

Ctrough is the serum concentration immediately prior to the next drug administration.

Time Frame

Up to 3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: For acute myeloid leukemia (AML) participants: AML according to World Health Organization (WHO) 2016 criteria and fulfilling all of the following criteria:(a) more than or equal to (>=) 75 years of age, or younger participants who are not eligible for or not willing to receive an intensive treatment (including stem cell transplantation) with curative intent and (b) previously untreated AML (except: emergency leukapheresis, low dose of cytarabine and/or hydroxyurea during the screening phase to control hyperleukocytosis but must be discontinued at least one day prior to start of cusatuzumab [Part 1] or azacitidine [Part 2]). All trans retinoic acid (ATRA) treatment for presumed acute promyelocytic leukemia (APL) is permitted but must be discontinued at least 1 day prior to the start of cusatuzumab (Part 1) or azacitidine (Part 2) For Myelodysplastic Syndrome (MDS) participants (only for Part 2): MDS according to WHO 2016 criteria and fulfilling all of the following criteria: (a) Not eligible for or not willing to receive allogenic stem cell transplantation,(b) very high or high-risk MDS according to Revised International Prognostic Scoring System (IPSS-R) and (c) previously untreated MDS (except: transfusion and/or cytokine therapy including erythropoietin) Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2 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 A woman of childbearing potential must have a negative highly sensitive serum (beta human chorionic gonadotropin [beta hCG]) or urine pregnancy at screening Exclusion Criteria: Acute promyelocytic leukemia (APL) with t (15;17), or its molecular equivalent promyelocytic leukemia retinoic acid receptor (PML RAR alpha) Leukemic involvement or clinical symptoms of leukemic involvement of the central nervous system Known allergies, hypersensitivity, or intolerance to cusatuzumab or azacitidine or its excipients (example, mannitol, an excipient of azacitidine) Prior treatment with a hypomethylating agent for treatment of AML or MDS A diagnosis of other malignancy that requires concurrent nonsurgical treatment

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Janssen Pharmaceutical K.K., Japan Clinical Trial

Organizational Affiliation

Janssen Pharmaceutical K.K.

Official's Role

Study Director

Facility Information:

Facility Name

Fukushima Medical University Hospital

City

Fukushima

ZIP/Postal Code

960-1295

Country

Japan

Facility Name

Gunmaken Saiseikai Maebashi Hospital

City

Maebashi

ZIP/Postal Code

371-0821

Country

Japan

Facility Name

Osaka City General Hospital

City

Osaka

ZIP/Postal Code

534-0021

Country

Japan

Facility Name

NTT Medical Center Tokyo

City

Tokyo

ZIP/Postal Code

141-8625

Country

Japan

Facility Name

University of Fukui Hospital

City

Yoshida

ZIP/Postal Code

910-1193

Country

Japan

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Learn more about this trial

A Study of Cusatuzumab Plus Azacitidine in Japanese Participants With Newly Diagnosed Acute Myeloid Leukemia or High-risk Myelodysplastic Syndrome Who Are Not Candidates for Intensive Treatment

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