Clinical Trials /

Dose Escalation Study of JNJ-63709178, a Humanized CD123 x CD3 DuoBody in Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML)

NCT02715011

Description:

The purpose of this study is to characterize the safety and tolerability of JNJ-63709178 and identify the recommended Phase 2 dose(s) (RP2D) and schedule for JNJ-63709178 in Part 1 and to characterize the safety and tolerability of JNJ-63709178 at the RP2D(s) in Part 2.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Dose Escalation Study of JNJ-63709178, a Humanized CD123 x CD3 DuoBody in Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML)
  • Official Title: A Phase 1, First-in-Human, Open-Label, Dose Escalation Study of JNJ-63709178, a Humanized CD123 x CD3 DuoBody in Subjects With Relapsed or Refractory AML

Clinical Trial IDs

  • ORG STUDY ID: CR108147
  • SECONDARY ID: 63709178AML1001
  • SECONDARY ID: 2016-000208-27
  • NCT ID: NCT02715011

Conditions

  • Leukemia, Myeloid, Acute

Interventions

DrugSynonymsArms
JNJ-63709178Part 1: Dose Escalation

Purpose

The purpose of this study is to characterize the safety and tolerability of JNJ-63709178 and identify the recommended Phase 2 dose(s) (RP2D) and schedule for JNJ-63709178 in Part 1 and to characterize the safety and tolerability of JNJ-63709178 at the RP2D(s) in Part 2.

Detailed Description

      This is first-in-human (FIH) Phase 1, open-label (identity of assigned study drug will be
      known), multicenter, dose escalation study with dose expansion to identify the RP2D and to
      evaluate the safety, tolerability, and preliminary antitumor activity of JNJ-63709178 in
      adult participants with relapsed or refractory acute myeloid leukemia (AML) who are
      ineligible for or have exhausted standard therapeutic options. The study is divided into 3
      periods: a Screening Phase (within 28 days before the first dose of study drug), a Treatment
      Phase (first dose of study drug until the last dose of study drug) and a Post-treatment
      Follow-up Phase (up to the end of study participation or end of study). Participants' safety
      will be monitored throughout the study.
    

Trial Arms

NameTypeDescriptionInterventions
Part 1: Dose EscalationExperimentalThe first cohort of participants will receive intravenous infusions of JNJ-63709178. Each subsequent cohort will receive intravenous infusions of JNJ-63709178 at an increased dose level. Dose escalation will continue until the maximum tolerated dose is reached or all planned doses are administered. Participants will receive intravenous infusion of JNJ-63709178 every two weeks or more frequently. The cycle duration is 21-35 days. Ascending doses may be given initially to minimize or prevent cytokine release syndrome.
  • JNJ-63709178
Part 2: Dose ExpansionExperimentalParticipants will receive intravenous infusion of JNJ-63709178 at the recommended Phase 2 dose(s) (RP2D).
  • JNJ-63709178

Eligibility Criteria

        Inclusion Criteria:

          -  A diagnosis of acute myeloid leukemia (AML) according to the World Health Organization
             2008 criteria with relapsed or refractory disease and ineligible for or have exhausted
             standard therapeutic options

          -  Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1

          -  Hematology laboratory parameters within the Protocol specified range

          -  Chemistry laboratory parameters within the Protocol specified range

          -  A woman of childbearing potential must have a negative highly sensitive serum (beta
             human chorionic gonadotropin [b-hCG]) or urine test prior to the first dose of study
             drug

        Exclusion Criteria:

          -  Acute promyelocytic leukemia

          -  Active central nervous system involvement

          -  Prior solid organ transplantation

          -  Prior hematopoietic stem cell transplant within 6 months of enrollment. If the
             participant had an allogenic transplant there must be no apparent signs of graft
             versus host disease and participants must have discontinued all immunosuppressive
             therapies for at least 4 weeks

          -  Prior treatment with a CD123xCD3 bispecific agent, T cells expressing CD123 specific
             chimeric antigen receptor, or toxin-conjugated to CD123 antibodies; prior treatment
             with naked anti-CD123 monoclonal antibody is permitted
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part 1: Number of participants with dose-limiting toxicity (DLT)
Time Frame:Up to Day 28
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Part 2: Serum concentration of JNJ-63709178
Time Frame:Up to 1.5 years
Safety Issue:
Description:
Measure:Part 2: JNJ-63709178 Receptor occupancy
Time Frame:Up to 1.5 years
Safety Issue:
Description:
Measure:Part 2: Number of participants with depletion of CD123 expressing cells
Time Frame:Up to 1.5 years
Safety Issue:
Description:
Measure:Part 2: Systemic cytokine concentration
Time Frame:Up to 1.5 years
Safety Issue:
Description:
Measure:Part 2: Concentration of markers of T cell activation
Time Frame:Up to 1.5 years
Safety Issue:
Description:
Measure:Part 2: Anti- JNJ-63709178 antibodies concentration
Time Frame:Up to 1.5 years
Safety Issue:
Description:
Measure:Part 2: Overall response rate (ORR)
Time Frame:Up to 1.5 years
Safety Issue:
Description:ORR rate is defined as the rate of complete response (CR) plus CR with incomplete recovery (CRi) or CR with partial hematologic recovery (CRh).
Measure:Part 2: Event-free survival (EFS)
Time Frame:Up to 1.5 years
Safety Issue:
Description:EFS is defined as time from start of treatment to the date of an event, that is, first documented treatment failure, relapse from CR, CRi, or CRh, or death due to any cause.
Measure:Part 2: Relapse-free survival (RFS)
Time Frame:Up to 1.5 years
Safety Issue:
Description:RFS is defined as time from CR, CRi, or CRh confirmed objective response to relapse from CR, CRi, or CRh or death from any cause.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Janssen Research & Development, LLC

Trial Keywords

  • Leukemia, Myeloid, Acute
  • JNJ-63709178

Last Updated

January 2, 2020