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

NCT02743546 | Withdrawn Phase 1 FDA Drug

• 3 other identifiers: CR10815864052781NHL10012016-000721-39
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

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

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  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.

  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.

  Baseline and 2 years

Secondary Outcomes (16)

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

  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

  Approximately 2 years

• Part 1 and 2: Maximum Serum Concentration (Cmax) of Duvortuxizumab

  Approximately 2 years

• Part 1 and 2: Maximum Serum Concentration (Cmax) of Ibrutinib

  Approximately 2 years

• Part 1 and 2: Half-Life (t1/2) of Duvortuxizumab

  Approximately 2 years

Study Arms (5)

Dose Optimization:Participant with Certain B-Cell Malignancies

EXPERIMENTAL

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.

Drug: Duvortuxizumab; Drug: Ibrutinib

Dose Expansion: Participants with DLBCL

EXPERIMENTAL

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.

Drug: Duvortuxizumab; Drug: Ibrutinib

Dose Expansion: Participants with FL

EXPERIMENTAL

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.

Drug: Duvortuxizumab; Drug: Ibrutinib

Dose Expansion: Participants with MCL

EXPERIMENTAL

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.

Drug: Duvortuxizumab; Drug: Ibrutinib

Dose Expansion: Participants with CLL

EXPERIMENTAL

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.

Drug: Duvortuxizumab; Drug: Ibrutinib

Interventions

Duvortuxizumab 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.

Dose Expansion: Participants with CLL; Dose Expansion: Participants with DLBCL; Dose Expansion: Participants with FL; Dose Expansion: Participants with MCL; Dose Optimization:Participant with Certain B-Cell Malignancies

Ibrutinib 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; Dose Expansion: Participants with DLBCL; Dose Expansion: Participants with FL; Dose Expansion: Participants with MCL; Dose Optimization:Participant with Certain B-Cell Malignancies

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Neoplasms; Bronchiolitis Obliterans Syndrome

Interventions

ibrutinib

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2016
• First Posted: April 19, 2016
• Study Start: July 20, 2016
• Primary Completion: September 30, 2018
• Study Completion: March 31, 2020
• Last Updated: February 3, 2025

Record last verified: 2025-01