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

Leukemia, Myeloid, Acute Clinical Trial

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 Details — Status: Completed

Administrative data

• NCT number: NCT02715011
• Other study ID #: CR108147
• Secondary ID: 63709178AML10012
• Status: Completed
• Phase: Phase 1
• Start date: June 1, 2016
• Est. completion date: March 26, 2021

Study information

• Verified date: August 2021
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: March 26, 2021
• Est. primary completion date: March 26, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• JNJ-63709178
Participants will receive JNJ-63709178 in Part 1 and Part 2.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Number of participants with dose-limiting toxicity (DLT)		Up to Day 28
Primary	Part 1: Type of dose-limiting toxicity (DLT)		Up to Day 28
Primary	Part 2: Number of participants with adverse events and serious adverse events		Up to 1.5 years
Primary	Part 2: Number of participants with adverse events by severity		Up to 1.5 years
Secondary	Part 2: Serum concentration of JNJ-63709178		Up to 1.5 years
Secondary	Part 2: JNJ-63709178 Receptor occupancy		Up to 1.5 years
Secondary	Part 2: Number of participants with depletion of CD123 expressing cells		Up to 1.5 years
Secondary	Part 2: Systemic cytokine concentration		Up to 1.5 years
Secondary	Part 2: Concentration of markers of T cell activation		Up to 1.5 years
Secondary	Part 2: Anti- JNJ-63709178 antibodies concentration		Up to 1.5 years
Secondary	Part 2: Overall response rate (ORR)	ORR rate is defined as the rate of complete response (CR) plus CR with incomplete recovery (CRi) plus CR with partial hematologic recovery (CRh).	Up to 1.5 years
Secondary	Part 2: Event-free survival (EFS)	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.	Up to 1.5 years
Secondary	Part 2: Relapse-free survival (RFS)	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.	Up to 1.5 years