Clinical Trials /

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

NCT04241549

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: CR108732
  • SECONDARY ID: 74494550AML1002
  • NCT ID: NCT04241549

Conditions

  • Leukemia, Myeloid, Acute

Interventions

DrugSynonymsArms
CusatuzumabJNJ-74494550, ARGX-110Part 1 (Dose Finding): Cusatuzumab + Azacitidine
AzacitidineVIDAZAPart 1 (Dose Finding): Cusatuzumab + Azacitidine

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Part 1 (Dose Finding): Cusatuzumab + AzacitidineExperimentalParticipants 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.
  • Cusatuzumab
  • Azacitidine
Part 2 (Dose Expansion): Cusatuzumab + AzacitidineExperimentalParticipants 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.
  • Cusatuzumab
  • Azacitidine

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 a 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 azacitidine

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:20 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part 1 and Part 2: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame:Up to 3 years
Safety Issue:
Description:Number of participants with AEs and SAEs will be reported.

Secondary Outcome Measures

Measure:Part 1 and Part 2: Percentage of Participants with Complete Response (CR)
Time Frame:Up to 9 months
Safety Issue:
Description: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.
Measure:Part 1: Objective Response Rate (ORR)
Time Frame:Up to 6 months
Safety Issue:
Description:ORR is defined as percentage of participants with CR, CRh and CRi based on response criteria per investigator assessment in participants with AML.
Measure:Part 2: Objective Response Rate (ORR)
Time Frame:Up to 9 months
Safety Issue:
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.
Measure:Part 2: Percentage of Participants with Hematologic Improvement (HI)
Time Frame:Up to 9 months
Safety Issue:
Description:Percentage of participants with hematologic improvement will be reported according to response criteria per investigator assessment in participants with MDS.
Measure:Part 1 and Part 2: Time to Response
Time Frame:Up to 3 years
Safety Issue:
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..
Measure:Part 1 and Part 2: Duration of Response
Time Frame:Up to 3 years
Safety Issue:
Description: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.
Measure:Part 1 and Part 2: Red Blood Cell (RBC) or Platelets Transfusion Independence
Time Frame:Up to 3 years
Safety Issue:
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.
Measure:Part 1 and Part 2: Overall Survival (OS)
Time Frame:Up to 3 years
Safety Issue:
Description:OS is defined as the time from initial study intervention administration to death from any cause.
Measure:Part 1 and Part 2: Maximum Serum Concentration (Cmax) of Cusatuzumab
Time Frame:Up to 3 years
Safety Issue:
Description:Cmax is the maximum observed serum concentration.
Measure:Part 1 and Part 2: Serum Trough Concentration (Ctrough) of Cusatuzumab
Time Frame:Up to 3 years
Safety Issue:
Description:Ctrough is the serum concentration immediately prior to the next drug administration.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Janssen Pharmaceutical K.K.

Last Updated

April 2, 2020