Study of the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of Duvortuxizumab (JNJ-64052781) Plus Ibrutinib in Lymphoma

NCT ID: NCT02743546

Last Updated: 2025-02-03

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-07-20
• Study Completion Date: 2020-03-31

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.

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Lymphoma, Mantle-Cell

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose Optimization:Participant with Certain B-Cell Malignancies

Participants with certain B-cell malignancies (diffuse large B-cell lymphoma \[DLBCL\], mantle cell lymphoma \[MCL\], or follicular lymphoma \[FL\]) will receive rising doses of intravenous infusions of duvortuxizumab either with or without a priming dose in combination with oral ibrutinib until disease progression, unacceptable toxicity, or other protocol-specified withdrawal criteria are met. Dose escalation will continue until the recommended phase 2 dose or maximum tolerated dose is reached.

Group Type: EXPERIMENTAL

Duvortuxizumab

Intervention Type: DRUG

Duvortuxizumab will be administered at starting dose of 15 nanogram per kilogram (ng/kg) as an intravenous (IV) infusion during Part 1 (Dose Optimization) and at RP2D level determined in Part 1 during Part 2 (Dose Expansion). Participants will receive duvortuxizumab either with or without a priming dose. Participants who receive a priming dose will have infusions on Days 1, 8, and 22 of an initial 35-day cycle and then on Days 1 and 15 of 28-day cycles thereafter. Participants who do not receive a priming dose will have infusions on Days 1 and 15 of 28-day cycles.

Ibrutinib

Intervention Type: DRUG

Ibrutinib will be administered at 560 milligram per day (mg/day) orally once daily during Part 1 (Dose Optimization) and at a dose of 420 mg/day (for participants with CLL) or 560 mg/day (for participants with DLBCL, FL, or MCL) during Part 2 (Dose Expansion). In Part 1, ibrutinib will be initiated on Day 1 of the initial treatment cycle. In Part 2, ibrutinib will be initiated on Day -7 prior to the initial treatment cycle.

Dose Expansion: Participants with DLBCL

Participants with DLBCL will receive intravenous infusions of duvortuxizumab either with or without a priming dose in combination with oral ibrutinib at the recommended phase 2 dose until disease progression, unacceptable toxicity, or other protocol-specified withdrawal criteria are met.

Group Type: EXPERIMENTAL

Duvortuxizumab

Intervention Type: DRUG

Duvortuxizumab will be administered at starting dose of 15 nanogram per kilogram (ng/kg) as an intravenous (IV) infusion during Part 1 (Dose Optimization) and at RP2D level determined in Part 1 during Part 2 (Dose Expansion). Participants will receive duvortuxizumab either with or without a priming dose. Participants who receive a priming dose will have infusions on Days 1, 8, and 22 of an initial 35-day cycle and then on Days 1 and 15 of 28-day cycles thereafter. Participants who do not receive a priming dose will have infusions on Days 1 and 15 of 28-day cycles.

Ibrutinib

Intervention Type: DRUG

Ibrutinib will be administered at 560 milligram per day (mg/day) orally once daily during Part 1 (Dose Optimization) and at a dose of 420 mg/day (for participants with CLL) or 560 mg/day (for participants with DLBCL, FL, or MCL) during Part 2 (Dose Expansion). In Part 1, ibrutinib will be initiated on Day 1 of the initial treatment cycle. In Part 2, ibrutinib will be initiated on Day -7 prior to the initial treatment cycle.

Dose Expansion: Participants with FL

Participants with FL will receive intravenous infusions of duvortuxizumab either with or without a priming dose in combination with oral ibrutinib at the recommended phase 2 dose until disease progression, unacceptable toxicity, or other protocol-specified withdrawal criteria are met.

Group Type: EXPERIMENTAL

Duvortuxizumab

Intervention Type: DRUG

Duvortuxizumab will be administered at starting dose of 15 nanogram per kilogram (ng/kg) as an intravenous (IV) infusion during Part 1 (Dose Optimization) and at RP2D level determined in Part 1 during Part 2 (Dose Expansion). Participants will receive duvortuxizumab either with or without a priming dose. Participants who receive a priming dose will have infusions on Days 1, 8, and 22 of an initial 35-day cycle and then on Days 1 and 15 of 28-day cycles thereafter. Participants who do not receive a priming dose will have infusions on Days 1 and 15 of 28-day cycles.

Ibrutinib

Intervention Type: DRUG

Ibrutinib will be administered at 560 milligram per day (mg/day) orally once daily during Part 1 (Dose Optimization) and at a dose of 420 mg/day (for participants with CLL) or 560 mg/day (for participants with DLBCL, FL, or MCL) during Part 2 (Dose Expansion). In Part 1, ibrutinib will be initiated on Day 1 of the initial treatment cycle. In Part 2, ibrutinib will be initiated on Day -7 prior to the initial treatment cycle.

Dose Expansion: Participants with MCL

Participants with MCL will receive intravenous infusions of duvortuxizumab either with or without a priming dose in combination with oral ibrutinib at the recommended phase 2 dose until disease progression, unacceptable toxicity, or other protocol-specified withdrawal criteria are met.

Group Type: EXPERIMENTAL

Duvortuxizumab

Intervention Type: DRUG

Duvortuxizumab will be administered at starting dose of 15 nanogram per kilogram (ng/kg) as an intravenous (IV) infusion during Part 1 (Dose Optimization) and at RP2D level determined in Part 1 during Part 2 (Dose Expansion). Participants will receive duvortuxizumab either with or without a priming dose. Participants who receive a priming dose will have infusions on Days 1, 8, and 22 of an initial 35-day cycle and then on Days 1 and 15 of 28-day cycles thereafter. Participants who do not receive a priming dose will have infusions on Days 1 and 15 of 28-day cycles.

Ibrutinib

Intervention Type: DRUG

Ibrutinib will be administered at 560 milligram per day (mg/day) orally once daily during Part 1 (Dose Optimization) and at a dose of 420 mg/day (for participants with CLL) or 560 mg/day (for participants with DLBCL, FL, or MCL) during Part 2 (Dose Expansion). In Part 1, ibrutinib will be initiated on Day 1 of the initial treatment cycle. In Part 2, ibrutinib will be initiated on Day -7 prior to the initial treatment cycle.

Dose Expansion: Participants with CLL

Participants with chronic lymphocytic leukemia (CLL) will receive intravenous infusions of duvortuxizumab either with or without a priming dose in combination with oral ibrutinib at the recommended phase 2 dose until disease progression, unacceptable toxicity, or other protocol-specified withdrawal criteria are met.

Group Type: EXPERIMENTAL

Duvortuxizumab

Intervention Type: DRUG

Duvortuxizumab will be administered at starting dose of 15 nanogram per kilogram (ng/kg) as an intravenous (IV) infusion during Part 1 (Dose Optimization) and at RP2D level determined in Part 1 during Part 2 (Dose Expansion). Participants will receive duvortuxizumab either with or without a priming dose. Participants who receive a priming dose will have infusions on Days 1, 8, and 22 of an initial 35-day cycle and then on Days 1 and 15 of 28-day cycles thereafter. Participants who do not receive a priming dose will have infusions on Days 1 and 15 of 28-day cycles.

Ibrutinib

Intervention Type: DRUG

Ibrutinib will be administered at 560 milligram per day (mg/day) orally once daily during Part 1 (Dose Optimization) and at a dose of 420 mg/day (for participants with CLL) or 560 mg/day (for participants with DLBCL, FL, or MCL) during Part 2 (Dose Expansion). In Part 1, ibrutinib will be initiated on Day 1 of the initial treatment cycle. In Part 2, ibrutinib will be initiated on Day -7 prior to the initial treatment cycle.

Interventions

Duvortuxizumab

Duvortuxizumab will be administered at starting dose of 15 nanogram per kilogram (ng/kg) as an intravenous (IV) infusion during Part 1 (Dose Optimization) and at RP2D level determined in Part 1 during Part 2 (Dose Expansion). Participants will receive duvortuxizumab either with or without a priming dose. Participants who receive a priming dose will have infusions on Days 1, 8, and 22 of an initial 35-day cycle and then on Days 1 and 15 of 28-day cycles thereafter. Participants who do not receive a priming dose will have infusions on Days 1 and 15 of 28-day cycles.

Intervention Type: DRUG

Ibrutinib

Ibrutinib will be administered at 560 milligram per day (mg/day) orally once daily during Part 1 (Dose Optimization) and at a dose of 420 mg/day (for participants with CLL) or 560 mg/day (for participants with DLBCL, FL, or MCL) during Part 2 (Dose Expansion). In Part 1, ibrutinib will be initiated on Day 1 of the initial treatment cycle. In Part 2, ibrutinib will be initiated on Day -7 prior to the initial treatment cycle.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Other Identifiers

64052781NHL1001

Identifier Type: OTHER

Identifier Source: secondary_id

2016-000721-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR108158

Identifier Type: -

Identifier Source: org_study_id