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.
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
Interventions
| Drug | Synonyms | Arms |
|---|
| JNJ-63709178 | | Part 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 will be conducted in
2 parts: dose escalation and dose expansion. 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
| Name | Type | Description | Interventions |
|---|
| Part 1: Dose Escalation | Experimental | Participants will receive JNJ-63709178 in Part 1 (in different cohorts). Each subsequent cohort will receive JNJ-63709178 at an increased dose level. Ascending doses may be given initially to minimize or prevent cytokine release syndrome. Dose escalation will continue until the maximum tolerated dose is reached or all planned doses are administered. | |
| Part 2: Dose Expansion | Experimental | Participants will receive JNJ-63709178 at the recommended Phase 2 dose(s) (RP2D) determined in dose expansion phase. | |
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) plus 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
February 26, 2021
