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

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ClinicalTrials.gov Identifier: NCT02538614
Recruitment Status : Terminated
First Posted : September 2, 2015
Last Update Posted : October 23, 2018
Sponsor:
Collaborator:
Boehringer Ingelheim
Information provided by (Responsible Party):
Gilead Sciences

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 maximum 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.

The Phase 2 portion of this study will not occur.


Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia (CLL) Drug: Idelalisib Drug: BI 836826 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b/2 Study of Idelalisib in Combination With BI 836826 in Subjects With Chronic Lymphocytic Leukemia
Actual Study Start Date : December 29, 2015
Actual Primary Completion Date : July 5, 2017
Actual Study Completion Date : July 5, 2017


Arm Intervention/treatment
Experimental: Phase 1b Idelalisib + BI 836826
Participants will receive escalating doses of idelalisib + BI 836826. 2 dose combinations (highRP2D and lowRP2D) will be determined for further evaluations in Phase 2.
Drug: Idelalisib
Idelalisib tablets administered orally twice daily
Other Names:
  • GS-1101
  • CAL-101
  • Zydelig®

Drug: BI 836826
BI 836826 will be administered intravenously from Week 2 through Week 46.

Experimental: Phase 2 Idelalisib + BI 836826
Participants will be randomly assigned to receive 1 of the 2 dose combinations selected from Phase 1b.
Drug: Idelalisib
Idelalisib tablets administered orally twice daily
Other Names:
  • GS-1101
  • CAL-101
  • Zydelig®

Drug: BI 836826
BI 836826 will be administered intravenously from Week 2 through Week 46.




Primary Outcome Measures :
  1. For Phase 1b, incidence rate of dose limiting toxicity (DLTs) during the first 7 weeks of study therapy at each combination dose level tested [ Time Frame: Up to 7 weeks ]
    Due to the early study termination, the endpoint will not be met and the participants enrolled will be assessed for safety only.

  2. For Phase 2, complete response rate (CRR) [ Time Frame: Up to 6 years ]
    Complete response rate (CRR) is defined as the proportion of participants who achieve a complete response (CR). Due to the early study termination, the endpoint will not be met and the participants enrolled will be assessed for safety only.

  3. For Phase 2, minimal residual disease (MRD) negativity rate in bone marrow by Week 50 [ Time Frame: Up to Week 50 ]
    Minimal residual disease (MRD) defined as the proportion of participants with MRD < 10^-4, assessed by flow cytometry in bone marrow, achieved by Week 50. Due to the early study termination, the endpoint will not be met and the participants enrolled will be assessed for safety only.


Secondary Outcome Measures :
  1. For Phase 1b, incidence rate of dose limiting toxicity during the treatment period [ Time Frame: Up to 6 years ]
    Due to the early study termination, the endpoint will not be met and the subjects enrolled will be assessed for safety only.

  2. For Phase 1b and Phase 2, serious adverse events (SAE), or AE leading to discontinuation of study treatment [ Time Frame: Up to 6 years ]
    Due to the early study termination, the endpoint will not be met and the participants enrolled will be assessed for safety only.

  3. For Phase 2, overall response rate (ORR) [ Time Frame: Up to 6 years ]
    Overall response rate (ORR) is defined as the proportion of participants who achieve a CR or partial response (PR). Due to the early study termination, the endpoint will not be met and the participants enrolled will be assessed for safety only.

  4. For Phase 2, duration of complete response (DCR) [ Time Frame: Up to 6 years ]
    Duration of complete response (DCR) is defined as the interval from the first documentation of CR to the earlier of the first documentation of definitive disease progression or death from any cause. Due to the early study termination, the endpoint will not be met and the participants enrolled will be assessed for safety only.

  5. For Phase 2, duration of response (DOR) [ Time Frame: Up to 6 years ]
    Duration of response (DOR) is defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of definitive disease progression or death from any cause. Due to the early study termination, the endpoint will not be met and the participants enrolled will be assessed for safety only.

  6. For Phase 2, progression-free survival (PFS) [ Time Frame: Up to 6 years ]
    Progression-free survival (PFS) is defined as the interval from randomization to the earlier of the first documentation of definitive disease progression or death from any cause. Due to the early study termination, the endpoint will not be met and the participants enrolled will be assessed for safety only.

  7. For Phase 2, overall survival (OS) [ Time Frame: Up to 6 years ]
    Overall survival defined as the interval from the randomization to the date of death from any cause. Due to the early study termination, the endpoint will not be met and the participants enrolled will be assessed for safety only.

  8. For Phase 2, MRD negativity rate in blood at any time [ Time Frame: Up to 6 years ]
    MRD negativity rate in blood is defined as the proportion of participants with MRD < 10^-4, assessed by flow cytometry in blood, at any time on study. Due to the early study termination, the endpoint will not be met and the participants enrolled will be assessed for safety only.

  9. For Phase 2, MRD negativity rate in bone marrow at any time [ Time Frame: Up to 6 years ]
    MRD negativity rate in bone marrow is defined as the proportion of participants with MRD < 10^-4, assessed by flow cytometry in bone marrow, at any time on study. Due to the early study termination, the endpoint will not be met and the participants enrolled will be assessed for safety only.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02538614


Locations
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United States, Ohio
Ohio State University
Columbus, Ohio, United States
United States, Utah
University of Utah
Salt Lake City, Utah, United States
Sponsors and Collaborators
Gilead Sciences
Boehringer Ingelheim
Investigators
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Study Director: Gilead Study Director Gilead Sciences

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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02538614     History of Changes
Other Study ID Numbers: GS-US-312-1579
First Posted: September 2, 2015    Key Record Dates
Last Update Posted: October 23, 2018
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at http://www.gilead.com/research/disclosure-and-transparency.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: 18 months after study completion
Access Criteria: A secured external environment with username, password, and RSA code.
URL: http://www.gilead.com/research/disclosure-and-transparency

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Idelalisib
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
BI 836826
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological