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

NCT02538614 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: GS-US-312-1579
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 2

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)

Outcome Measures

Primary Outcomes (3)

• Phase 1b: Percentage of Participants Experienced Dose Limiting Toxicities (DLTs) During the First 7 Weeks of Study Therapy

  DLTs refer to toxicities experienced during the final 6 weeks of 7-week study treatment that have been judged to be clinically significant and related to study treatment. Events occurring during the initial 7-day idelalisib monotherapy run-in period and resolving by Day 8 were not included.

  Up to 7 weeks

• For Phase 2: Complete Response Rate (CRR)

  CRR was defined as the percentage of participants who achieve a complete response (CR). CR was defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease.

  Up to 18 months

• For Phase 2: Minimal Residual Disease (MRD) Negativity Rate in Bone Marrow by Week 50

  MRD defined as the percentage of participants with MRD \< 10\^-4, assessed by flow cytometry in bone marrow, achieved by Week 50.

  Week 50

Secondary Outcomes (10)

• Phase 1b: Percentage of Participants Experienced DLTs During the Treatment Period

  Up to 18 months

• For Phase 1b and Phase 2: Number of Participants Experiencing Any Serious Adverse Events (SAE)

  Up to 18 months

• For Phase 1b and Phase 2: Number of Participants Who Permanently Discontinued Study Treatment Due to an Adverse Event

  Up to 18 months

• For Phase 2: Overall Response Rate (ORR)

  Up to 18 months

• For Phase 2: Duration of Complete Response (DCR)

  Up to 18 months

Study Arms (2)

Phase 1b: Idelalisib + BI 836826

EXPERIMENTAL

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.

Drug: Idelalisib; Drug: BI 836826

Phase 2 Idelalisib + BI 836826

EXPERIMENTAL

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

Drug: Idelalisib; Drug: BI 836826

Interventions

Idelalisib DRUG

Tablets administered orally twice daily

Also known as: GS-1101, CAL-101, Zydelig®

Phase 1b: Idelalisib + BI 836826; Phase 2 Idelalisib + BI 836826

BI 836826 DRUG

Intravenous administration as a rate-controlled infusion

Phase 1b: Idelalisib + BI 836826; Phase 2 Idelalisib + BI 836826

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gilead Sciences: lead
• Boehringer Ingelheim: collaborator

Study Sites (2)

Ohio State University

Columbus, Ohio, United States

Location

University of Utah

Salt Lake City, Utah, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

idelalisib; BI 836826

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1b: sequential assignment, Phase 2: parallel assignment

Study Record Dates

• First Submitted: August 31, 2015
• First Posted: September 2, 2015
• Study Start: December 29, 2015
• Primary Completion: July 5, 2017
• Study Completion: July 5, 2017
• Last Updated: November 25, 2020
• Results First Posted: November 25, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.

Locations

US (2)