Clinical trial NCT02715011: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Leukemia, Myeloid, Acute
Keywords: Leukemia, Myeloid, Acute
JNJ-63709178
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2016-03-22
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

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

Primary outcomes:
measure: Part 1: Number of participants with dose-limiting toxicity (DLT)
timeFrame: Up to Day 28
measure: Part 1: Type of dose-limiting toxicity (DLT)
timeFrame: Up to Day 28
measure: Part 2: Number of participants with adverse events and serious adverse events
timeFrame: Up to 1.5 years
measure: Part 2: Number of participants with adverse events by severity
timeFrame: Up to 1.5 years
Secondary outcomes:
measure: Part 2: Serum concentration of JNJ-63709178
timeFrame: Up to 1.5 years
measure: Part 2: JNJ-63709178 Receptor occupancy
timeFrame: Up to 1.5 years
measure: Part 2: Number of participants with depletion of CD123 expressing cells
timeFrame: Up to 1.5 years
measure: Part 2: Systemic cytokine concentration
timeFrame: Up to 1.5 years
measure: Part 2: Concentration of markers of T cell activation
timeFrame: Up to 1.5 years
measure: Part 2: Anti- JNJ-63709178 antibodies concentration
timeFrame: Up to 1.5 years
measure: Part 2: Overall response rate (ORR)
timeFrame: Up to 1.5 years
measure: Part 2: Event-free survival (EFS)
timeFrame: Up to 1.5 years
measure: Part 2: Relapse-free survival (RFS)
timeFrame: Up to 1.5 years
Other outcomes:
Locations:
city: Detroit
country: United States
state: Michigan
city: New York
country: United States
state: New York
city: Charlotte
country: United States
state: North Carolina
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Nashville
country: United States
state: Tennessee
city: Houston
country: United States
state: Texas
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Sevilla
country: Spain
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: