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

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

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.

Study Overview

• Status: Completed
• Conditions: Leukemia, Myeloid, Acute
• Intervention / Treatment: Drug: Cusatuzumab; Drug: Azacitidine

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Fukushima, Japan, 960-1295
    • Fukushima Medical University Hospital
  • Maebashi, Japan, 371-0821
    • Gunmaken Saiseikai Maebashi Hospital
  • Osaka, Japan, 534-0021
    • Osaka City General Hospital
  • Tokyo, Japan, 141-8625
    • NTT Medical Center Tokyo
  • Yoshida, Japan, 910-1193
    • University of Fukui Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 (Dose Finding): Cusatuzumab + Azacitidine; 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.	Drug: Cusatuzumab; Cusatuzumab at a dose 20 milligram per kilogram (mg/kg) once every 2 weeks will be administered intravenously.; Other Names: ARGX-110; JNJ-74494550; Drug: Azacitidine; Azacitidine at a dose 75 milligram per square meters (mg/m^2) will be administered subcutaneously or intravenously.; Other Names: VIDAZA
Experimental: Part 2 (Dose Expansion): Cusatuzumab + Azacitidine; 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.	Drug: Cusatuzumab; Cusatuzumab at a dose 20 milligram per kilogram (mg/kg) once every 2 weeks will be administered intravenously.; Other Names: ARGX-110; JNJ-74494550; Drug: Azacitidine; Azacitidine at a dose 75 milligram per square meters (mg/m^2) will be administered subcutaneously or intravenously.; Other Names: VIDAZA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 3 years
Part 1 and Part 2: Number of Participants with Dose-Limiting Toxicity (DLTs)	Number of participants with DLTs will be reported.	Up to 42 days
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.	Up to 42 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 9 months
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.	Up to 6 months
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.	Up to 9 months
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.	Up to 9 months
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..	Up to 3 years
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.	Up to 3 years
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.	Up to 3 years
Part 1 and Part 2: Overall Survival (OS)	OS is defined as the time from initial study intervention administration to death from any cause.	Up to 3 years
Part 1 and Part 2: Maximum Serum Concentration (Cmax) of Cusatuzumab	Cmax is the maximum observed serum concentration.	Up to 3 years
Part 1 and Part 2: Serum Trough Concentration (Ctrough) of Cusatuzumab	Ctrough is the serum concentration immediately prior to the next drug administration.	Up to 3 years

Collaborators and Investigators

• Sponsor: OncoVerity, Inc.
• Collaborators: Janssen Pharmaceutical K.K.; argenx
• Investigators: Study Director: Janssen Pharmaceutical K.K., Japan Clinical Trial, Janssen Pharmaceutical K.K.

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2020
• Primary Completion (Actual): July 19, 2021
• Study Completion (Actual): July 19, 2021

Study Registration Dates

• First Submitted: January 23, 2020
• First Submitted That Met QC Criteria: January 23, 2020
• First Posted (Actual): January 27, 2020

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; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Azacitidine
• Other Study ID Numbers: CR108732; 74494550AML1002 (Other Identifier: Janssen Pharmaceutical K.K., Japan)

Plan for Individual participant data (IPD)

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

IPD 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
• product manufactured in and exported from the U.S.: Yes