NCT02077166|CompletedPhase 1ResultsDMC

Ibrutinib in Combination With Lenalidomide and Rituximab in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

A Multicenter Open-Label Phase 1b/2 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, in Combination With Lenalidomide and Rituximab in Subjects With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Pharmacyclics LLC.ClinicalTrials.gov

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2 other identifiers

PCYC-1123-CA2013-004341-17

Study Type

interventional

Target

138

Locations

4 countries

Sites

Timeline

RegisteredMar 2014

StartedMar 2014

CompletionDec 2020

Brief Summary

This Phase 1b/2 study is designed to assess the safety and efficacy of ibrutinib in combination with lenalidomide and rituximab in subjects with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) not eligible for transplant.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

138

participants targeted

Target at P75+ for phase_1

Timeline

Completed

Started Mar 2014

Longer than P75 for phase_1

Geographic Reach

4 countries

40 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

6.8 years study duration

First Submitted

Initial submission to the registry

February 10, 2014

Completed

22 days until next milestone

First Posted

Study publicly available on registry

March 4, 2014

Completed

9 days until next milestone

Study Start

First participant enrolled

March 13, 2014

Completed

6.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 17, 2020

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 17, 2020

Completed

1.1 years until next milestone

Results Posted

Study results publicly available

February 4, 2022

Completed

Last Updated

February 4, 2022

Status Verified

January 1, 2022

Enrollment Period

6.8 years

First QC Date

February 10, 2014

Results QC Date

November 30, 2021

Last Update Submit

January 6, 2022

Conditions

Relapsed Diffuse Large B-Cell Lymphoma Refractory Diffuse Large B-Cell Lymphoma

Keywords

DLBCL

Outcome Measures

Primary Outcomes (3)

Phase 1b: Recommended Phase 2 Dose of Lenalidomide in Combination With Fixed Doses of Ibrutinib and Rituximab in Participants With Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL)
The dose levels of lenalidomide were explored, and dose escalation of lenalidomide followed the 3+3+3 dose escalation schema. A Dose Level Review Committee evaluated safety data following completion of each dose observation period of the Phase 1b portion.
Estimated median time on study in Phase 1b was 59.6 months.
Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs
An adverse event (AE) is any untoward medical occurrence, which does not necessarily have a causal relationship with treatment. A serious AE is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires in-patient hospitalization \> 24 hours or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is an important medical event. AEs that started or worsened during the treatment-emergent period and all possibly related or related AEs were considered TEAEs. Related events were those that were considered possibly related or related to study drug per investigator's judgment. Events were graded per the national Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.03: Grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=life-threatening; grade 5=death.
From first dose of study drug up to 30 days after last dose of study drug. Phase 1b median duration of ibrutinib exposure was 4.4 months; median duration of lenalidomide exposure was 4.4 months; median total number of doses of rituximab received was 4.0.
Phase 2: Overall Response Rate (ORR)
The ORR was defined as the percentage of participants who achieve either a partial response (PR) or complete response (CR), according to the Revised International Working Group Response Criteria for Malignant Lymphoma or Lugano Classification (Cheson 2014), as assessed by the investigator in response-evaluable population. The 95% confidence interval (CI) was calculated using the exact method.
Estimated median time on study in Phase 2 was 35.0 months.

Secondary Outcomes (7)

Phase 1b: ORR
Estimated median time on study in Phase 1b was 59.6 months.
Phase 1b: Complete Response (CR) Rate
Estimated median time on Phase 1b study was 59.6 months.
Phase 2: CR Rate
Estimated median time on study in Phase 2 was 35.0 months.
Phase 2: Duration of Response (DOR)
Estimated median time on study in Phase 2 was 35.0 months.
Phase 2: Progression Free Survival (PFS)
Estimated median time on study in Phase 2 was 35.0 months.
+2 more secondary outcomes

Study Arms (7)

Phase 1b: Enrolled at Lenalidomide Dose 15 mg (Dose Level 1)

EXPERIMENTAL

Ibrutinib 560 mg administered orally (PO) once daily (QD) beginning Cycle 1 Day 1 until disease progression or unacceptable toxicity. Lenalidomide 15 mg administered PO QD on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity. Rituximab 375 mg/m\^2 administered intravenously (IV) on Day 1 of each 28-day cycle for 6 cycles.