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

Janssen Research & Development, LLC

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Conditions

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

Interventions

DuvortuxizumabDRUG

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.

IbrutinibDRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Part 1: Number of Participants With Dose Limiting Toxicity

Dose limiting toxicity is based on adverse events and includes unacceptable hematologic toxicity, unacceptable non-hematologic toxicity, and laboratory abnormalities of Grade 4 or higher.

Time frame: Approximately 9 months

Part 1 and Part 2: Number of Participants With Adverse Events

An adverse event (AE) is any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship.

Time frame: Approximately 2 years

Part 1 and Part 2: Number of Participants With Serious Adverse Events

A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital abnormality.

Time frame: Approximately 2 years

Part 1 and Part 2: Change in Clinical Laboratory Values From Baseline

Standard clinical chemistry and hematology panels will be used to evaluate changes in laboratory parameters in blood samples collected pre- and post-treatment.

Time frame: Baseline and 2 years

Secondary Outcomes

Part 1 and Part 2: Area Under the Serum Concentration-Time Curve From Time [0 to t] (AUC[0-t]) of Duvortuxizumab

The AUC\[0-t\] is the area under the duvortuxizumab serum concentration-time curve from time \[0 to t\].

Time frame: Approximately 2 years

Part 1 and Part 2: Area Under the Serum Concentration-Time Curve From Time [0 to t] (AUC[0-t]) of Ibrutinib

Data from ClinicalTrials.gov

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