Study of Idelalisib in Combination With BI 836826 in Participants With Chronic Lymphocytic Leukemia

NCT ID: NCT02538614

Last Updated: 2020-11-25

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-29
• Study Completion Date: 2017-07-05

Brief Summary

This study consists of 2 parts: Phase 1b and Phase 2. Phase 1b will evaluate the safety and tolerability of the combination of idelallisib with the anti-CD37 monoclonal antibody BI 836826 in participants with relapsed/refractory chronic lymphocytic leukemia (R/R CLL), and establish the high recommended Phase 2 combination dose (highRP2D) as well as an alternate lower recommended Phase 2 combination dose (lowRP2D). Phase 2 will determine the rates of complete response (CR) and of minimal residual disease (MRD) negativity with the combination at the highRP2D and the lowRP2D in participants with R/R CLL.

Conditions

Chronic Lymphocytic Leukemia (CLL)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1b: Idelalisib + BI 836826

Participants will receive escalating dose of idelalisib at dose levels, 50 mg, 100 mg, and 150 mg + BI 836826 10 mg on Day 8, 50 mg on Day 9 and Day 15, and 100 mg on Day 22, every 2 weeks through Week 18, and every 4 weeks through Week 46. 2 dose combinations (highRP2D and lowRP2D) will be determined for further evaluations in Phase 2.

Group Type: EXPERIMENTAL

Idelalisib

Intervention Type: DRUG

Tablets administered orally twice daily

BI 836826

Intervention Type: DRUG

Intravenous administration as a rate-controlled infusion

Phase 2 Idelalisib + BI 836826

Participants will be randomly assigned to receive 1 of the 2 dose combinations selected from Phase 1b.

Group Type: EXPERIMENTAL

Idelalisib

Intervention Type: DRUG

Tablets administered orally twice daily

BI 836826

Intervention Type: DRUG

Intravenous administration as a rate-controlled infusion

Interventions

Idelalisib

Tablets administered orally twice daily

Intervention Type: DRUG

BI 836826

Intravenous administration as a rate-controlled infusion

Intervention Type: DRUG

Other Intervention Names

GS-1101; CAL-101; Zydelig®

Eligibility Criteria

Inclusion Criteria

• Diagnosis of B-cell CLL, established according to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria and having received at least 2 prior treatment regimens
• CLL that warrants treatment
• Clinically quantifiable disease burden defined as:

• For Phase 1b individuals: absolute lymphocyte count (ALC) > 5000/μL in peripheral blood.
• For Phase 2 individuals either:

• At least 1 node ≥ 2 cm on computed tomography (CT) or magnetic resonance imaging (MRI) or
• bone marrow exam is performed at screening and demonstrates quantifiable CLL.
• Discontinuation of all cytotoxic chemotherapy and anti-CD20 antibody therapy for ≥ 4 weeks, alemtuzumab for ≥ 8 weeks, targeted therapy for ≥ 2 weeks, and investigational therapy for ≥ 3 weeks before enrollment (Phase 1b) or randomization (Phase 2). For individuals with relapsed CLL most recently treated with B-cell receptor (BCR) pathway inhibitors who, in the opinion of the investigator, will not tolerate waiting 3 weeks, a washout period of > 5 half-lives is allowed. If on a systemic corticosteroid, the dose must be stable for the previous 4 weeks.
• Eastern Cooperative Oncology Group (ECOG) score of ≤ 2

Exclusion Criteria

• Known histological transformation from CLL to an aggressive lymphoma (ie, Richter transformation)
• Known presence of myelodysplastic syndrome
• History of a non-CLL malignancy except for the following: adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate-specific antigen for ≥ 1 year prior to enrollment, other adequately treated Stage 1 or 2 cancer currently in complete remission, or any other cancer that has been in complete remission for ≥ 2 years.
• Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of enrollment
• Ongoing drug-induced liver injury, chronic active hepatitis C (HCV), chronic active hepatitis B (HBV), alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension.
• History of drug-induced pneumonitis
• Ongoing inflammatory bowel disease
• Ongoing alcohol or drug addiction
• History of prior allogeneic bone marrow progenitor cell or solid organ transplantation
• Ongoing systemic immunosuppressive therapy other than corticosteroids
• History of prior therapy with any phosphatidylinositol 3-kinase (PI3K) inhibitor (including idelalisib), or any anti-CD37 agent
• Ongoing infection with, or treatment or prophylaxis for, CMV within the past 28 days.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: collaborator

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

Ohio State University

Columbus, Ohio, United States

University of Utah

Salt Lake City, Utah, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

GS-US-312-1579

Identifier Type: -

Identifier Source: org_study_id