ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02715011
Recruitment Status : Suspended (Study on hold due to Grade 3 event.)
First Posted : March 22, 2016
Last Update Posted : August 13, 2018
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

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.

Condition or disease Intervention/treatment Phase
Leukemia, Myeloid, Acute Drug: JNJ-63709178 Phase 1

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 subjects 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). Subjects' safety will be monitored throughout the study.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 1, 2016
Estimated Primary Completion Date : October 29, 2020
Estimated Study Completion Date : April 28, 2021


Arm Intervention/treatment
Experimental: Part 1: Dose Escalation
The first cohort of subjects 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. Subjects will receive intravenous infusion of JNJ-63709178 every two weeks or more frequently. The cycle duration is 21-28 days. Ascending doses may be given initially to minimize or prevent cytokine release syndrome.
Drug: JNJ-63709178
Intravenous infusion of JNJ-63709178 every two weeks or more frequently. The duration of each treatment cycle is 21-28 days.

Experimental: Part 2: Dose Expansion
Subjects will receive intravenous infusion of JNJ-63709178 at the recommended Phase 2 dose(s) (RP2D).
Drug: JNJ-63709178
Intravenous infusion of JNJ-63709178 every two weeks or more frequently. The duration of each treatment cycle is 21-28 days.




Primary Outcome Measures :
  1. Part 1: Number of subjects with dose-limiting toxicity (DLT) [ Time Frame: Up to Day 28 ]
  2. Part 1: Type of dose-limiting toxicity (DLT) [ Time Frame: Up to Day 28 ]
  3. Part 2: Occurence of adverse events and serious adverse events [ Time Frame: Up to 1.5 years ]
  4. Part 2: Severity of adverse events and serious adverse events [ Time Frame: Up to 1.5 years ]

Secondary Outcome Measures :
  1. Part 2: Serum concentration of JNJ-63709178 [ Time Frame: Up to 1.5 years ]
  2. Part 2: JNJ-63709178 Receptor occupancy [ Time Frame: Up to 1.5 years ]
  3. Part 2: Number of subjects with depletion of CD123 expressing cells [ Time Frame: Up to 1.5 years ]
  4. Part 2: Systemic cytokine concentration [ Time Frame: Up to 1.5 years ]
  5. Part 2: Concentration of markers of T cell activation [ Time Frame: Up to 1.5 years ]
  6. Part 2: Anti- JNJ-63709178 antibodies concentration [ Time Frame: Up to 1.5 years ]
  7. Part 2: Overall response rate (ORR) [ Time Frame: Up to 1.5 years ]
    ORR rate is defined as the rate of complete response (CR) plus CR with incomplete recovery (CRi).

  8. Part 2: Event-free survival (EFS) [ Time Frame: Up to 1.5 years ]
    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 death due to any cause.

  9. Part 2: Relapse-free survival (RFS) [ Time Frame: Up to 1.5 years ]
    RFS is defined as time from CR or CRi confirmed objective of response to relapse from CR or CRi or to death from any cause.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 subject had an allogenic transplant there must be no apparent signs of graft versus host disease and subjects 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02715011


Locations
United States, Colorado
Aurora, Colorado, United States
United States, Michigan
Detroit, Michigan, United States
United States, New York
New York, New York, United States
United States, North Carolina
Charlotte, North Carolina, United States
United States, Pennsylvania
Philadelphia, Pennsylvania, United States
Pittsburgh, Pennsylvania, United States
United States, Tennessee
Nashville, Tennessee, United States
United States, Texas
Houston, Texas, United States
Spain
Barcelona, Spain
Madrid, Spain
Sevilla, Spain
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT02715011     History of Changes
Other Study ID Numbers: CR108147
63709178AML1001 ( Other Identifier: Janssen Research & Development, LLC )
2016-000208-27 ( EudraCT Number )
First Posted: March 22, 2016    Key Record Dates
Last Update Posted: August 13, 2018
Last Verified: August 2018

Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Janssen Research & Development, LLC:
Leukemia, Myeloid, Acute
JNJ-63709178

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms