Clinical trial NCT02743546: Study of the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of Duvortuxizumab (JNJ-64052781) Plus Ibrutinib in Lymphoma
Official title: A Phase 1b Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of the Combination of Duvortuxizumab With Ibrutinib in Subjects With B-Cell Malignancies
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Follicular
Lymphoma, Mantle-Cell
Keywords: B-Cell, Malignancy
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Mantle-Cell
Lymphoma, Follicular
Lymphocytic, Chronic, B-Cell
JNJ-64052781
Ibrutinib
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2016-04-19
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether duvortuxizumab and ibrutinib can be combined safely and to establish the maximum tolerated dose (MTD) in Part 1 and the recommended Phase 2 dose (RP2D) and to further explore the safety of duvortuxizumab in combination with ibrutinib at the RP2D in participants with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and chronic lymphocytic leukemia (CLL) in Part 2.

Detailed description: This is an open-label (identity of study drug will be known to participant and study staff), multicenter (when more than one hospital or medical school team work on a medical research study), Phase 1b study. The purpose of this study is to see if duvortuxizumab in combination with ibrutinib is safe and useful for treating participants with B-cell malignancies. This study will be conducted in 2 parts: Part 1: Dose Optimization and Part 2: Dose Expansion. Part 1 will determine what dose of duvortuxizumab can be given safely with the standard dose of ibrutinib to participants with previously treated B-cell malignancies. Part 2 will look at how previously treated DLBCL, FL, MCL, and CLL participants respond to a safe dose of duvortuxizumab in combination with ibrutinib. Part 2 will also test whether the dose from Part 1 is an effective cancer therapy. The study consists of a Screening Phase, an ibrutinib Run-In Phase (Part 2 only), a combination (duvortuxizumab plus ibrutinib) Treatment Phase (Day 1, Cycle 1 and continues until the completion of the End-of-Treatment Visit), End-of-Treatment Visit (30 days (+7 days) after the last dose of study drug), and Post-treatment Follow-up Phase. The end of the study will be defined as 12 months after the last participant has received the first dose of study treatment. Participants' safety will be monitored throughout the study.

Eligibility criteria: Inclusion Criteria:

* The participant has a B-cell malignancy (diffuse large B-cell lymphoma \[DLBCL\], follicular lymphoma \[FL\], mantle cell lymphoma \[MCL\], or chronic lymphocytic leukemia \[CLL\]) with tumor progression following at least one (MCL and CLL) or two (DLBCL and FL) prior standard therapies
* The participant has a radiographically measurable tumor that requires treatment according to the treating physician
* The participant is able to carry out daily life activities with significant difficulty
* The participant has adequate organ and blood cell counts
* Sexually active participants must use medically acceptable methods of contraception during the course of the study

Exclusion Criteria:

* The participant has a brain tumor or significant side effects, including severe neurological side effects, from a previous anti-cancer treatment
* Current severe, uncontrolled systemic disease including an ongoing, active infection or history of clinically significant heart problems
* History of autoimmune disease, allogeneic hematopoietic stem cell transplant, or organ transplant
* The participant has received any of the following: ibrutinib or other Bruton's tyrosine kinase (BTK) inhibitor at any time; an agent targeting CD19-positive cells or CD3-expressing T cells at any time; or warfarin, a vitamin K antagonist, or a blood transfusion (red blood cells and/or platelets) within 1 week of starting the study
* The participant is pregnant, breastfeeding, or planning to become pregnant or father a child

Primary outcomes:
measure: Part 1: Number of Participants With Dose Limiting Toxicity
timeFrame: Approximately 9 months
measure: Part 1 and Part 2: Number of Participants With Adverse Events
timeFrame: Approximately 2 years
measure: Part 1 and Part 2: Number of Participants With Serious Adverse Events
timeFrame: Approximately 2 years
measure: Part 1 and Part 2: Change in Clinical Laboratory Values From Baseline
timeFrame: Baseline and 2 years
Secondary outcomes:
measure: Part 1 and Part 2: Area Under the Serum Concentration-Time Curve From Time [0 to t] (AUC[0-t]) of Duvortuxizumab
timeFrame: Approximately 2 years
measure: Part 1 and Part 2: Area Under the Serum Concentration-Time Curve From Time [0 to t] (AUC[0-t]) of Ibrutinib
timeFrame: Approximately 2 years
measure: Part 1 and 2: Maximum Serum Concentration (Cmax) of Duvortuxizumab
timeFrame: Approximately 2 years
measure: Part 1 and 2: Maximum Serum Concentration (Cmax) of Ibrutinib
timeFrame: Approximately 2 years
measure: Part 1 and 2: Half-Life (t1/2) of Duvortuxizumab
timeFrame: Approximately 2 years
measure: Part 1 and 2: Half-Life (t1/2) of Ibrutinib
timeFrame: Approximately 2 years
measure: Part 1 and 2: Total Systemic Clearance (CL) of Duvortuxizumab
timeFrame: Approximately 2 years
measure: Part 1 and 2: Total Systemic Clearance (CL) of Ibrutinib
timeFrame: Approximately 2 years
measure: Part 1 and 2: Volume of Distribution at Steady-State (Vss) of Duvortuxizumab
timeFrame: Approximately 2 years
measure: Part 1 and 2: Volume of Distribution at Steady-State (Vss) of Ibrutinib
timeFrame: Approximately 2 years
measure: Part 1 and Part 2: Number of Participants with Anti-Duvortuxizumab Antibodies
timeFrame: Approximately 2 years
measure: Part 1 and Part 2: Objective Tumor Response
timeFrame: Approximately 2 years
measure: Part 1 and Part 2: Number of Participants With Complete Response (CR)
timeFrame: Approximately 2 years
measure: Part 1 and Part 2: Duration of Response
timeFrame: Approximately 2 years
measure: Part 1 and Part 2: 1-year Progression Free Survival (PFS)
timeFrame: 1 year
measure: Part 1 and Part 2: 1-year Overall Survival
timeFrame: 1 year
Other outcomes:
Locations:
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: