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

Lymphoma, Large B-Cell, Diffuse Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02743546
• Other study ID #: CR108158
• Secondary ID: 64052781NHL10012
• Status: Withdrawn
• Phase: Phase 1
• First received: April 15, 2016
• Last updated: November 22, 2017
• Start date: July 20, 2016
• Est. completion date: March 31, 2020

Study information

• Verified date: November 2017
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: March 31, 2020
• Est. primary completion date: September 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	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].	Approximately 2 years
Secondary	Part 1 and Part 2: Area Under the Serum Concentration-Time Curve From Time [0 to t] (AUC[0-t]) of Ibrutinib	The AUC[0-t] is the area under the ibrutinib serum concentration-time curve from time [0 to t].	Approximately 2 years
Secondary	Part 1 and 2: Maximum Serum Concentration (Cmax) of Duvortuxizumab	The Cmax is the maximum observed serum concentration of duvortuxizumab.	Approximately 2 years
Secondary	Part 1 and 2: Maximum Serum Concentration (Cmax) of Ibrutinib	The Cmax is the maximum observed serum concentration of ibrutinib.	Approximately 2 years
Secondary	Part 1 and 2: Half-Life (t1/2) of Duvortuxizumab	The elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration.	Approximately 2 years
Secondary	Part 1 and 2: Half-Life (t1/2) of Ibrutinib	The elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration.	Approximately 2 years
Secondary	Part 1 and 2: Total Systemic Clearance (CL) of Duvortuxizumab	The CL is a quantitative measure of the rate at which duvortuxizumab is removed from the body.	Approximately 2 years
Secondary	Part 1 and 2: Total Systemic Clearance (CL) of Ibrutinib	The CL is a quantitative measure of the rate at which ibrutinib is removed from the body.	Approximately 2 years
Secondary	Part 1 and 2: Volume of Distribution at Steady-State (Vss) of Duvortuxizumab	The Vss is defined as the theoretical volume in which the total amount of duvortuxizumab would be uniformly distributed to produce the desired serum concentration of duvortuxizumab at steady state.	Approximately 2 years
Secondary	Part 1 and 2: Volume of Distribution at Steady-State (Vss) of Ibrutinib	The Vss is defined as the theoretical volume in which the total amount of ibrutinib would be uniformly distributed to produce the desired serum concentration of Ibrutinib at steady state.	Approximately 2 years
Secondary	Part 1 and Part 2: Number of Participants with Anti-Duvortuxizumab Antibodies	Plasma levels of antibodies to duvortuxizumab will be assessed for evaluation of potential immunogenicity.	Approximately 2 years
Secondary	Part 1 and Part 2: Objective Tumor Response	Objective tumor response is represented by participants who achieve a complete response (CR) or partial response (PR) to study treatment per the criteria for response assessment of Non-Hodgkin's Lymphoma (participants with diffuse large B-cell lymphoma [DLBCL], follicular lymphoma [FL], and mantle cell lymphoma [MCL]) or the International Workshop on chronic lymphocytic leukemia Criteria (IWCLL) (participants with CLL)	Approximately 2 years
Secondary	Part 1 and Part 2: Number of Participants With Complete Response (CR)	The CR rate is frequency of participants who achieve a complete response to study treatment according to the Criteria for Response Assessment of Non-Hodgkin's Lymphoma (participants with DLBCL, FL, and MCL) or the IWCLL Criteria (for participants with CLL).	Approximately 2 years
Secondary	Part 1 and Part 2: Duration of Response	The Duration of Response is defined as the time from the first observed response (CR or partial response [PR]) to documented disease progression or death due to any cause.	Approximately 2 years
Secondary	Part 1 and Part 2: 1-year Progression Free Survival (PFS)	Progression free survival is defined as the time from first enrollment into the study to documented disease progression or death due to any cause.	1 year
Secondary	Part 1 and Part 2: 1-year Overall Survival	One-year survival is defined as the percentage of participants surviving 1 year after entering into the study.	1 year