Clinical trial NCT02538614: Study of Idelalisib in Combination With BI 836826 in Participants With Chronic Lymphocytic Leukemia
Official title: A Phase 1b/2 Study of Idelalisib in Combination With BI 836826 in Subjects With Chronic Lymphocytic Leukemia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Chronic Lymphocytic Leukemia (CLL)
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
Collaborators: name: Boehringer Ingelheim
First posted: 2015-09-02
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase 1b: sequential assignment, Phase 2: parallel assignment
Primary purpose: TREATMENT

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.


Eligibility criteria: Key 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

Key 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.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Phase 1b: Percentage of Participants Experienced Dose Limiting Toxicities (DLTs) During the First 7 Weeks of Study Therapy
timeFrame: Up to 7 weeks
measure: For Phase 2: Complete Response Rate (CRR)
timeFrame: Up to 18 months
measure: For Phase 2: Minimal Residual Disease (MRD) Negativity Rate in Bone Marrow by Week 50
timeFrame: Week 50
Secondary outcomes:
measure: Phase 1b: Percentage of Participants Experienced DLTs During the Treatment Period
timeFrame: Up to 18 months
measure: For Phase 1b and Phase 2: Number of Participants Experiencing Any Serious Adverse Events (SAE)
timeFrame: Up to 18 months
measure: For Phase 1b and Phase 2: Number of Participants Who Permanently Discontinued Study Treatment Due to an Adverse Event
timeFrame: Up to 18 months
measure: For Phase 2: Overall Response Rate (ORR)
timeFrame: Up to 18 months
measure: For Phase 2: Duration of Complete Response (DCR)
timeFrame: Up to 18 months
measure: For Phase 2: Duration of Response (DOR)
timeFrame: Up to 18 months
measure: For Phase 2: Progression-Free Survival (PFS)
timeFrame: Up to 18 months
measure: For Phase 2: Overall Survival (OS)
timeFrame: Up to 18 months
measure: For Phase 2: MRD Negativity Rate in Blood at Any Time
timeFrame: Up to 18 months
measure: For Phase 2: MRD Negativity Rate in Bone Marrow at Any Time
timeFrame: Up to 18 months
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: