Diffuse Large B-Cell LymphomaPhase 1/2NCT02401048

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

A Phase 1/2 study testing Ibrutinib and MEDI4736 in people with Diffuse Large B-Cell Lymphoma and Follicular Lymphoma, run by Pharmacyclics LLC. at 11 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Diffuse Large B-Cell Lymphoma, Follicular Lymphoma
What is being tested?: Ibrutinib and MEDI4736
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 61 participants
Where: 11 sitesUnited States
Study dates: May 2015to Nov 2017
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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:
Absolute Neutrophil Count >1500 cells/mm3
Platelets >50000 cells/mm3
Hemoglobin >8.0 g/dL

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Adequate hepatic and renal function:
AST or ALT ≤2.5 x ULN
Bilirubin ≤1.5 x ULN
Estimated creatinine clearance (Cockcroft-Gault) >40 mL/min
ECOG 0 or 1

Who cannot join

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

Trial locations and contacts

11 sites in 1 country.

City, postcode or hospital

11 sites in 1 country

United States11 sites

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

Other trials in United States

About this study

Official title: 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.

Conditions: Diffuse Large B-Cell Lymphoma, Follicular Lymphoma
Being tested: Ibrutinib, MEDI4736
Medical subject headings: Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

IbrutinibDrug
MEDI4736Drug

Study groups in NCT02401048
Study group	Role	What they receive
Phase 1b/ 2: Follicular lymphoma expansion cohort	Experimental	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. Receives: Drug: Ibrutinib; Drug: MEDI4736
Phase 1b/ 2: Diffuse large B-cell lymphoma expansion cohort	Experimental	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. Receives: Drug: Ibrutinib; Drug: MEDI4736

What is being measured

The primary outcome is the main question the study is designed to answer.

Phase 1b/2 : Overall Response Rate of Number of Participants
The response criteria is measured based on the revised criteria for malignant lymphoma described by the International Working Group for NHL (Cheson 2014).
Measured: From the date of first study treatment until progressive disease

Secondary outcomes (14)

Phase 1b/ 2: Duration of Response
Measured: 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)
Measured: first dose date of study drug (ibrutinib or MEDI4736) to the first documentation of disease progression
Phase 1b/2: Overall Survival
Measured: 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
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)
Measured: 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 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)
Measured: 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
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)
Measured: 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
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)
Measured: 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
Peak plasma concentration of MEDI4736 on Cycle 6 Day 1 (ibrutinib + MEDI)
Measured: Cycle 6 Day 1 (collected 10 minutes after end of infusion)
Pharmacokinetics: Mean Trough Plasma Concentration (Ctrough) for MEDI4736
Trough plasma concentration of MEDI4736 on Cycle 6 Day 1 (ibrutinib + MEDI)
Measured: Cycle 6 Day 1 (predose)
Pharmacokinetics: MEDI4736 Accumulation Ratio for Cmax
Accumulation ratio from Cycle 6 Day 1 to Cycle 1 Day 1 for Cmax for MEDI4736
Measured: Cycle 6 Day 1 (collected 10 minutes after end of infusion)
Pharmacokinetics: MEDI4736 Accumulation Ratio for Ctrough
Accumulation ratio from Cycle 6 Day 1 to Cycle 1 Day 1 for Ctrough for MEDI4736
Measured: Cycle 6 Day 1 (predose)
Bruton Tyrosine Kinase (BTK) Occupancy
BTK occupancy
Measured: ibrutinib Lead-in Day 6 or 7 pre-dose
Pharmacodynamics of Ibrutinib in Subjects With Relapsed or Refractory Lymphomas
BTK occupancy
Measured: Cycle 3 Day 1 Pre-dose
Pharmacodynamics of MEDI4736 in Subjects With Relapsed or Refractory Lymphomas
Detectable Free Serum PD-L1 level
Measured: Cycle 3 Day1 Pre-dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2015Nov 2017

First posted27 Mar 2015 (estimated)
Study startMay 2015
Primary completionNov 2017
Study completionNov 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Diffuse Large B-Cell LymphomaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Factorial
Masking: None (open label)
Enrolment: 61 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02401048
Sponsor's protocol ID: PCYC-1136-CA
Status last verified: Jun 2019
First submitted: 4 Mar 2015
Last updated: 27 Jun 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 27 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT02401048
Acronym / sponsor ID: PCYC-1136-CA
Conditions: Diffuse Large B-Cell Lymphoma, Follicular Lymphoma
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 61 participants (actual)
Lead sponsor: Pharmacyclics LLC.Industry (pharma, biotech, devices)
Collaborators: AstraZeneca, Janssen Research & Development, LLC
Study start: May 2015
Primary completion: Nov 2017 (actual)
Study completion: Nov 2017 (actual)
First posted: 27 Mar 2015 (estimated)
Results: Posted 27 Jun 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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 design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Factorial
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Phase 1b/ 2: Follicular lymphoma expansion cohort	Experimental	Drug: Ibrutinib, Drug: MEDI4736In 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.
Phase 1b/ 2: Diffuse large B-cell lymphoma expansion cohort	Experimental	Drug: Ibrutinib, Drug: MEDI4736In 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

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:
Adequate hepatic and renal function:
ECOG 0 or 1

Key exclusion criteria (3 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Ibrutinib	Drug	Phase 1b/ 2: Diffuse large B-cell lymphoma expansion cohort, Phase 1b/ 2: Follicular lymphoma expansion cohort
MEDI4736	Drug	Phase 1b/ 2: Diffuse large B-cell lymphoma expansion cohort, Phase 1b/ 2: Follicular lymphoma expansion cohort

Primary outcome

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).

14 secondary outcomes

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.
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
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
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)
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)
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)
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)
Pharmacokinetics: Mean Peak Plasma Concentration (Cmax) for MEDI4736
Time frame: 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)
Pharmacokinetics: MEDI4736 Accumulation Ratio for Cmax
Time frame: Cycle 6 Day 1 (collected 10 minutes after end of infusion)
Pharmacokinetics: MEDI4736 Accumulation Ratio for Ctrough
Time frame: Cycle 6 Day 1 (predose)
Bruton Tyrosine Kinase (BTK) Occupancy
Time frame: 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
Pharmacodynamics of MEDI4736 in Subjects With Relapsed or Refractory Lymphomas
Time frame: Cycle 3 Day1 Pre-dose

Results and safety

Results posted to the registry on 27 Jun 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Phase 1b/ 2: Follicular Lymphoma Expansion Cohort	27	5
Phase 1b/ 2: Diffuse Large B-cell Lymphoma Expansion Cohort	34	4

Primary outcome: Phase 1b/2 : Overall Response Rate of Number of Participants

Time frame: From the date of first study treatment until progressive disease. Count of participants. Unit: Participants

Measure	Phase 1b/ 2: Follicular Lymphoma Expansion Cohort n = 27	Phase 1b/ 2: Diffuse Large B-cell Lymphoma Expansion Cohort n = 34
Value	7	8

Population analysed: While the study include Phase 1b and 2, the dosing was not changed between phases (following the study design because there were no DLTs and thus no dose adjustments in from Phase 1b to Phase 2). Thus the study data were reported with Phases 1b and 2 combined.

14 secondary outcomes are reported in the full results.

Adverse events

Time frame: All AEs, whether serious or non-serious, are documented in the source documents from the time the signed and dated ICF is obtained until 30 days following the last dose of ibrutinib and 90 days following the last dose of MEDI4736.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Phase 1b/2: Follicular Lymphoma Expansion Cohort:	10 of 27 (37%)	27 of 27 (100%)	6 of 27
Phase 1b/ 2: Diffuse Large B-cell Lymphoma Expansion Cohort:	23 of 34 (67.6%)	33 of 34 (97.1%)	24 of 34

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Emily Liu study director

Pharmacyclics LLC.

11 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Ibrutinib and MEDI4736 in people with Diffuse Large B-Cell Lymphoma and Follicular Lymphoma, run by Pharmacyclics LLC. at 11 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1b/2 : Overall Response Rate of Number of Participants (time frame: From the date of first study treatment until progressive disease). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02401048.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jun 2019.