A Multi-Center Study of Ibrutinib in Combination With MEDI4736 in Subjects With Relapsed or Refractory Lymphomas

June 3, 2019 updated by: Pharmacyclics LLC.

A Multi-Center Open-Label Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, in Combination With MEDI4736, in Subjects With Relapsed or Refractory Lymphomas

The purpose of this study is to evaluate the efficacy, safety and tolerability of the combination treatment of ibrutinib and MEDI4736 in subjects with relapsed or refractory lymphomas.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
61

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • Site-0397
    • California
      • Duarte, California, United States, 91010
        • Site-0047
      • Stanford, California, United States, 94305
        • Site-0038
    • Florida
      • Miami, Florida, United States, 33136
        • Site-0388
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Site-0126
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Site-0020/0173
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Site-0729
      • Detroit, Michigan, United States, 48201
        • Site-0130
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Site-0343
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Site-0402
    • Washington
      • Seattle, Washington, United States, 98104
        • Site-0114

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Pathologically documented relapsed or refractory diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL)
  • Measurable disease sites on CT scan (>1.5 cm in longest dimension)

  • Adequate hematologic function:

    1. Absolute Neutrophil Count >1500 cells/mm3
    2. Platelets >50000 cells/mm3
    3. Hemoglobin >8.0 g/dL

  • Adequate hepatic and renal function:

    1. AST or ALT ≤2.5 x ULN
    2. Bilirubin ≤1.5 x ULN
    3. Estimated creatinine clearance (Cockcroft-Gault) >40 mL/min
  • ECOG 0 or 1

Exclusion Criteria:

  • Received prior therapies: ibrutinib, or other BTK inhibitor and/or anti-PD1, anti-PD-L1, anti-PD-L2, anti-CD137, or CTLA-4 antibody
  • Requires treatment or prophylaxis with a strong cytochrome P450 (CYP) 3A inhibitor
  • Primary CNS lymphoma or evidence of CNS involvement by lymphoma

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: FACTORIAL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Phase 1b/ 2: Follicular lymphoma expansion cohort
In the Phase 1b (safety portion) of the study, a starting dose of 560 mg of ibrutinib and 10 mg/kg of MEDI4736 explored in cohort 1 and followed a 6+3 dose de-escalation design. Phase 2 used the phase 1b starting dose.
Drug: Ibrutinib
Drug: MEDI4736
EXPERIMENTAL: Phase 1b/ 2: Diffuse large B-cell lymphoma expansion cohort
In the Phase 1b (safety portion) of the study, a starting dose of 560 mg of ibrutinib and 10 mg/kg of MEDI4736 explored in cohort 1 and followed a 6+3 dose de-escalation design. Phase 2 used the phase 1b starting dose.
Drug: Ibrutinib
Drug: MEDI4736

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Phase 1b/2 : Overall Response Rate of Number of Participants
Time Frame: From the date of first study treatment until progressive disease
The response criteria is measured based on the revised criteria for malignant lymphoma described by the International Working Group for NHL (Cheson 2014).
From the date of first study treatment until progressive disease

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Phase 1b/ 2: Duration of Response
Time Frame: Time from the date of initial response to the date of disease progression or the date of death due to any cause, whichever occurs first.
Time from the date of initial response to the date of disease progression or the date of death due to any cause, whichever occurs first.
Phase 1b/ 2: Progression-free Survival (PFS)
Time Frame: first dose date of study drug (ibrutinib or MEDI4736) to the first documentation of disease progression
first dose date of study drug (ibrutinib or MEDI4736) to the first documentation of disease progression
Phase 1b/2: Overall Survival
Time Frame: First dose date of study drug (ibrutinib or MEDI4736) to the date of death due to any cause
First dose date of study drug (ibrutinib or MEDI4736) to the date of death due to any cause
Phamacokinetics: Mean Maximum Observed Plasma Concentration (Cmax) for Ibrutinib
Time Frame: Lead-In Day 6/7 or Cycle 3 Day 1 (collected at predose, 1, 2, 4, and 6 hours post-dose)
Maximum observed plasma concentration of ibrutinib during the dosing interval on Lead-In Day 6/7 (ibrutinib only) or Cycle 3 Day 1 (ibrutinib + MEDI)
Lead-In Day 6/7 or Cycle 3 Day 1 (collected at predose, 1, 2, 4, and 6 hours post-dose)
Pharmacokinetics: Mean Time to Maximum Observed Plasma Concentration (Tmax) for Ibrutinib
Time Frame: Lead-In Day 6/7 or Cycle 3 Day 1 (collected at predose, 1, 2, 4, and 6 hours post-dose)
Time to corresponding maximum observed plasma concentration of ibrutinib during the dosing interval on Lead-In Day 6/7 (ibrutinib only) or Cycle 3 Day 1 (ibrutinib + MEDI)
Lead-In Day 6/7 or Cycle 3 Day 1 (collected at predose, 1, 2, 4, and 6 hours post-dose)
Pharmacokinetics: Mean Area Under the Plasma Concentration-Time Curve From Time 0-24 Hours (AUC0-24h) for Ibrutinib
Time Frame: Lead-In Day 6/7 or Cycle 3 Day 1 (collected at predose, 1, 2, 4, and 6 hours post-dose)
Ibrutinib AUC0-24h calculated using linear trapezoidal summation after dosing from time 0 to 24 hours on Lead-In Day 6/7 (ibrutinib only) or Cycle 3 Day 1 (ibrutinib + MEDI)
Lead-In Day 6/7 or Cycle 3 Day 1 (collected at predose, 1, 2, 4, and 6 hours post-dose)
Pharmacokinetics: Mean Terminal Elimination Half-Life (t1/2,Term) for Ibrutinib
Time Frame: Lead-In Day 6/7 or Cycle 3 Day 1 (collected at predose, 1, 2, 4, and 6 hours post-dose)
Ibrutinib terminal elimination half-life associated with the terminal slope (λz) of the semi-logarithmic plasma concentration-time curve, calculated as 0.693/λz on Lead-In Day 6/7 (ibrutinib only) or Cycle 3 Day 1 (ibrutinib + MEDI)
Lead-In Day 6/7 or Cycle 3 Day 1 (collected at predose, 1, 2, 4, and 6 hours post-dose)
Pharmacokinetics: Mean Peak Plasma Concentration (Cmax) for MEDI4736
Time Frame: Cycle 6 Day 1 (collected 10 minutes after end of infusion)
Peak plasma concentration of MEDI4736 on Cycle 6 Day 1 (ibrutinib + MEDI)
Cycle 6 Day 1 (collected 10 minutes after end of infusion)
Pharmacokinetics: Mean Trough Plasma Concentration (Ctrough) for MEDI4736
Time Frame: Cycle 6 Day 1 (predose)
Trough plasma concentration of MEDI4736 on Cycle 6 Day 1 (ibrutinib + MEDI)
Cycle 6 Day 1 (predose)
Pharmacokinetics: MEDI4736 Accumulation Ratio for Cmax
Time Frame: Cycle 6 Day 1 (collected 10 minutes after end of infusion)
Accumulation ratio from Cycle 6 Day 1 to Cycle 1 Day 1 for Cmax for MEDI4736
Cycle 6 Day 1 (collected 10 minutes after end of infusion)
Pharmacokinetics: MEDI4736 Accumulation Ratio for Ctrough
Time Frame: Cycle 6 Day 1 (predose)
Accumulation ratio from Cycle 6 Day 1 to Cycle 1 Day 1 for Ctrough for MEDI4736
Cycle 6 Day 1 (predose)
Bruton Tyrosine Kinase (BTK) Occupancy
Time Frame: ibrutinib Lead-in Day 6 or 7 pre-dose
BTK occupancy
ibrutinib Lead-in Day 6 or 7 pre-dose
Pharmacodynamics of Ibrutinib in Subjects With Relapsed or Refractory Lymphomas
Time Frame: Cycle 3 Day 1 Pre-dose
BTK occupancy
Cycle 3 Day 1 Pre-dose
Pharmacodynamics of MEDI4736 in Subjects With Relapsed or Refractory Lymphomas
Time Frame: Cycle 3 Day1 Pre-dose
Detectable Free Serum PD-L1 level
Cycle 3 Day1 Pre-dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Pharmacyclics LLC.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
AstraZeneca
Janssen Research & Development, LLC

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Emily Liu, Pharmacyclics LLC.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2015

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2017

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 4, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 23, 2015

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 27, 2015

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 27, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 3, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PCYC-1136-CA

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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