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Study to Investigate Idelalisib in Combination With Chemotherapeutic Agents, Immunomodulatory Agents and Anti-CD20 Monoclonal Antibody (mAb) in Participants With Relapsed or Refractory Indolent B-cell Non-Hodgkin's Lymphoma, Mantle Cell Lymphoma or Chronic Lymphocytic Leukemia

Primary Purpose

Indolent Non-Hodgkin's Lymphoma, Chronic Lymphocytic Leukemia, Mantle Cell Lymphoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Idelalisib
Rituximab
Bendamustine
Ofatumumab
Fludarabine
Everolimus
Bortezomib
Chlorambucil
Lenalidomide
Sponsored by
Gilead Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Indolent Non-Hodgkin's Lymphoma focused on measuring phosphatidylinositol 3-kinase, Ofatumumab, indolent non-Hodgkin lymphoma (iNHL)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

  • Age ≥ 18
  • Previously treated with relapsed or refractory disease (refractory defined as not responding to a standard regimen or progressing within 6 months of the last course of a standard regimen)

  • Disease status requirement:

    • For CLL patients, symptomatic disease that mandates treatment as defined by the International Workshop on Chronic Lymphocytic Lymphoma (IWCLL) 2008 criteria
    • For indolent NHL and MCL patients, measurable disease by CT scan defined as at least 1 lesion that measures > 2 cm in a single dimension
  • WHO performance status of ≤ 2

  • For men and women of child-bearing potential, willing to use adequate contraception (ie, latex condom, cervical cap, diaphragm, abstinence, etc.) for the entire duration of the study.

    • For Cohort 7 only: Women of child bearing potential must have 2 negative pregnancy tests prior to starting lenalidomide.
  • Able to provide written informed consent

Key Exclusion Criteria:

  • Is not a good candidate to receive any of the drugs administered in the study for a given disease (idelalisib, bendamustine, rituximab, ofatumumab, fludarabine, everolimus, bortezomib, or chlorambucil), according to the clinical judgment of the investigator
  • Patients with atypical immunophenotype with t(11:14) translocation or cyclin D1 over-expression (CLL patients only)
  • Had radiotherapy, radioimmunotherapy, biological therapy, chemotherapy, or treatment with an investigational product within 4-weeks prior to the baseline disease status tests
  • Had treatment with a short course of corticosteroids for symptom relief within 1-week prior to the baseline disease status tests
  • Has had an allogeneic hematopoietic stem cell transplant
  • Has known active central nervous system involvement of the malignancy
  • Is pregnant or nursing
  • Has active, serious infection requiring systemic therapy. Patients may receive prophylactic antibiotics and antiviral therapy at the discretion of the investigator
  • Has absolute neutrophil count (ANC) < 1000/µL, unless it is related to underlying CLL, MCL or indolent NHL, the latter documented by > 50% infiltration of bone marrow by tumor cells
  • Has platelet count < 75000/µL, unless it is related to underlying CLL, MCL, or iNHL, the latter documented by > 50% infiltration of bone marrow by tumor cells

  • Has serum creatinine ≥ 2.0 mg/dL

    • For Cohort 7 only: Has creatinine clearance < 60 mL/min
  • Has serum bilirubin ≥ 2 mg/dL (unless due to Gilbert's syndrome) for patients with iNHL or CLL; for patients with MCL, serum bilirubin ≥ 1.5 x upper limit of normal
  • Has serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≥ 2 x upper limit of normal
  • Has Child-Pugh Class B or C hepatic impairment
  • Has a positive test for HIV antibodies
  • Has active hepatitis B or C (confirmed by RNA test). Patients with serologic evidence of prior exposure are eligible.
  • Prior treatment with idelalisib

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

Sites / Locations

  • Clearview Cancer Institute
  • UCLA
  • Stanford Cancer Center
  • Center for Cancer and Blood Disorders
  • Washington University School of Medicine
  • Long Island Jewish Medical Center
  • Weill Medical College of Cornell
  • Willamette Valley Cancer Institute and Research Center
  • Sarah Cannon Research Institute
  • MD Anderson Cancer
  • North Star Lodge Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Idelalisib + Rituximab

Idelalisib + Rituximab + Bendamustine

Idelalisib + Bendamustine

Idelalisib + Ofatumumab

Idelalisib + Fludarabine

Idelalisib + Everolimus

Idelalisib + Bortezomib

Idelalisib + Chlorambucil

Idelalisib + Rituximab + Chlorambucil

Idelalisib + Rituximab + Lenalidomide

Arm Description

Participants with chronic lymphocytic leukemia (CLL) and indolent non-Hodgkin lymphoma (iNHL) will receive treatments as follows: Cohort 1a: Idelalisib (IDELA) 100 mg orally twice daily (BID) on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 intravenously (IV) on Days 1, 8, 15 & 22, Cycles 1 & 2 Cohort 2a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2 Cohort 3e: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2 Cohort 4a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle, starting Cycle 2 Day 1 with the 5th dose of rituximab + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2

Participants with CLL, iNHL and mantle cell lymphoma (MCL) will receive treatments as follows: Cohort 3a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle from Cycles 1 - 6 Cohort 5c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Participants with CLL and iNHL will receive treatments as follows: Cohort 1b: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 2b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3f: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3g: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 4b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle starting Cycle 2, Day 3 (after the Cycle 2 bendamustine dosing) + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

Participants with CLL will receive treatments as follows: Cohort 3c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + ofatumumab 12 doses (300 mg (Day 1 or Day 2, Dose 1), followed 1 week later by 1,000 mg weekly for 7 doses (Doses 2 - 8), followed 5 weeks later by 1,000 mg every 4 weeks for 4 doses (Doses 9 - 12))

Participants with CLL will receive treatments as follows: Cohort 3d: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + fludarabine 40 mg/m^2 orally on Days 1 - 5 of each 28-day cycle, Cycles 1 - 6

Participants with MCL will receive treatments as follows: Cohort 5a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + everolimus 10 mg orally once daily on Days 1 - 28 of each 28-day cycle

Participants with MCL will receive treatments as follows: Cohort 5b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bortezomib 1.3 mg/m^2 subcutaneously on Days 1, 8 & 15 of each 28-day cycle

Participants with CLL will receive treatments as follows: Cohort 6a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12

Participants with CLL will receive treatments as follows: Cohort 6b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12

Participants with CLL and iNHL will receive treatments as follows: Cohort 7a: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) & Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of Cycle 1 & Day 1 of Cycles 2 - 6 + lenalidomide 5 mg orally once daily on Days 8 - 28 of Cycle 1 (35 days) & Days 1 - 21 of next five 28-day cycles Cohort 7b: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) & Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of Cycle 1 & Day 1 of Cycles 2 - 6 + lenalidomide 10 mg orally once daily on Days 8 - 28 of Cycle 1 (35 days) & Days 1 - 21 of next five 28-day cycles Cohort 7c: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) & Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of Cycle 1 & Day 1 of Cycles 2 - 6 + lenalidomide 20 mg orally once daily on Days 8 - 28 of Cycle 1 (35 days) & Days 1 - 21 of next five 28-day cycles

Outcomes

Primary Outcome Measures

Duration of Exposure to IDELA
Duration of exposure to IDELA was summarized using descriptive statistics.
Toxicity of Administration of IDELA
Percentage of participants experiencing toxicities of administration of IDELA were measured according to the Common Terminology Criteria for Adverse Events v4.02

Secondary Outcome Measures

Overall Response Rate
Overall Response Rate (ORR) was defined as the percentage of participants achieving a complete response (CR) or partial response (PR). The response definitions were based on the following standard criteria established for each indication: CLL: International Workshop on chronic lymphocytic leukemia (IWCLL),2008 iNHL & MCL: Cheson, 2007
Duration of Response
Duration of response (DOR) was defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of disease progression or death from any cause.
Time to Response
Time to response (TTR) was defined as the interval from the start of study drug to the first documentation of CR or PR.
Progression-free Survival
Progression free survival (PFS) was defined as the interval from the start of study drug to the earlier of the first documentation of disease progression or death from any cause. The response definitions were based on the following standard criteria established for each indication: CLL: International Workshop on chronic lymphocytic leukemia (IWCLL), 2008 iNHL & MCL: Cheson, 2007
Overall Survival
Overall Survival (OS) was defined as the interval from the start of study drug to death from any cause.
Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5)
Plasma Concentration of IDELA (Cohort 4)
Plasma Concentration of IDELA (Cohort 6)
Plasma Concentration of IDELA (Cohort 7)
Sub-study: Plasma Concentration of IDELA (Cohorts 1-4)
Plasma Concentration of Bendamustine
Plasma Concentration of Everolimus
Plasma Concentration of Lenalidomide

Full Information

First Posted
March 12, 2010
Last Updated
February 22, 2021
Sponsor
Gilead Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT01088048
Brief Title
Study to Investigate Idelalisib in Combination With Chemotherapeutic Agents, Immunomodulatory Agents and Anti-CD20 Monoclonal Antibody (mAb) in Participants With Relapsed or Refractory Indolent B-cell Non-Hodgkin's Lymphoma, Mantle Cell Lymphoma or Chronic Lymphocytic Leukemia
Official Title
A Phase I Study to Investigate the Safety and Clinical Activity of Idelalisib in Combination With Chemotherapeutic Agents, Immunomodulatory Agents and Anti-CD20 mAb in Subjects With Relapsed or Refractory Indolent B-cell Non-Hodgkin Lymphoma, Mantle Cell Lymphoma or Chronic Lymphocytic Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
March 25, 2010 (Actual)
Primary Completion Date
April 28, 2015 (Actual)
Study Completion Date
April 28, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The primary objective of the study is to evaluate the safety of idelalisib in combination with an anti-CD20 monoclonal antibody (mAb), a chemotherapeutic agent, a mammalian target of rapamycin (mTOR) inhibitor, a protease inhibitor, an antiangiogenic agent, and/or an immunomodulatory agent in participants with relapsed or refractory indolent B-cell non-Hodgkin lymphoma (NHL), mantle cell lymphoma (MCL), or chronic lymphocytic leukemia (CLL).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Indolent Non-Hodgkin's Lymphoma, Chronic Lymphocytic Leukemia, Mantle Cell Lymphoma
Keywords
phosphatidylinositol 3-kinase, Ofatumumab, indolent non-Hodgkin lymphoma (iNHL)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
241 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Idelalisib + Rituximab
Arm Type
Experimental
Arm Description
Participants with chronic lymphocytic leukemia (CLL) and indolent non-Hodgkin lymphoma (iNHL) will receive treatments as follows: Cohort 1a: Idelalisib (IDELA) 100 mg orally twice daily (BID) on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 intravenously (IV) on Days 1, 8, 15 & 22, Cycles 1 & 2 Cohort 2a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2 Cohort 3e: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2 Cohort 4a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle, starting Cycle 2 Day 1 with the 5th dose of rituximab + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2
Arm Title
Idelalisib + Rituximab + Bendamustine
Arm Type
Experimental
Arm Description
Participants with CLL, iNHL and mantle cell lymphoma (MCL) will receive treatments as follows: Cohort 3a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle from Cycles 1 - 6 Cohort 5c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6
Arm Title
Idelalisib + Bendamustine
Arm Type
Experimental
Arm Description
Participants with CLL and iNHL will receive treatments as follows: Cohort 1b: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 2b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3f: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3g: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 4b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle starting Cycle 2, Day 3 (after the Cycle 2 bendamustine dosing) + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6
Arm Title
Idelalisib + Ofatumumab
Arm Type
Experimental
Arm Description
Participants with CLL will receive treatments as follows: Cohort 3c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + ofatumumab 12 doses (300 mg (Day 1 or Day 2, Dose 1), followed 1 week later by 1,000 mg weekly for 7 doses (Doses 2 - 8), followed 5 weeks later by 1,000 mg every 4 weeks for 4 doses (Doses 9 - 12))
Arm Title
Idelalisib + Fludarabine
Arm Type
Experimental
Arm Description
Participants with CLL will receive treatments as follows: Cohort 3d: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + fludarabine 40 mg/m^2 orally on Days 1 - 5 of each 28-day cycle, Cycles 1 - 6
Arm Title
Idelalisib + Everolimus
Arm Type
Experimental
Arm Description
Participants with MCL will receive treatments as follows: Cohort 5a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + everolimus 10 mg orally once daily on Days 1 - 28 of each 28-day cycle
Arm Title
Idelalisib + Bortezomib
Arm Type
Experimental
Arm Description
Participants with MCL will receive treatments as follows: Cohort 5b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bortezomib 1.3 mg/m^2 subcutaneously on Days 1, 8 & 15 of each 28-day cycle
Arm Title
Idelalisib + Chlorambucil
Arm Type
Experimental
Arm Description
Participants with CLL will receive treatments as follows: Cohort 6a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12
Arm Title
Idelalisib + Rituximab + Chlorambucil
Arm Type
Experimental
Arm Description
Participants with CLL will receive treatments as follows: Cohort 6b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12
Arm Title
Idelalisib + Rituximab + Lenalidomide
Arm Type
Experimental
Arm Description
Participants with CLL and iNHL will receive treatments as follows: Cohort 7a: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) & Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of Cycle 1 & Day 1 of Cycles 2 - 6 + lenalidomide 5 mg orally once daily on Days 8 - 28 of Cycle 1 (35 days) & Days 1 - 21 of next five 28-day cycles Cohort 7b: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) & Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of Cycle 1 & Day 1 of Cycles 2 - 6 + lenalidomide 10 mg orally once daily on Days 8 - 28 of Cycle 1 (35 days) & Days 1 - 21 of next five 28-day cycles Cohort 7c: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) & Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of Cycle 1 & Day 1 of Cycles 2 - 6 + lenalidomide 20 mg orally once daily on Days 8 - 28 of Cycle 1 (35 days) & Days 1 - 21 of next five 28-day cycles
Intervention Type
Drug
Intervention Name(s)
Idelalisib
Other Intervention Name(s)
GS-1101, CAL-101, Zydelig®
Intervention Description
Idelalisib tablet administered orally
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Rituxan
Intervention Description
Rituximab administered intravenously
Intervention Type
Drug
Intervention Name(s)
Bendamustine
Other Intervention Name(s)
Treanda
Intervention Description
Bendamustine administered intravenously
Intervention Type
Drug
Intervention Name(s)
Ofatumumab
Other Intervention Name(s)
Arzerra
Intervention Description
Ofatumumab administered intravenously
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
Fludara
Intervention Description
Fludarabine administered orally
Intervention Type
Drug
Intervention Name(s)
Everolimus
Other Intervention Name(s)
Afinitor, RAD-001
Intervention Description
Everolimus administered orally twice daily until disease progression
Intervention Type
Drug
Intervention Name(s)
Bortezomib
Other Intervention Name(s)
Velcade, codenamed PS-341
Intervention Description
Bortezomib administered as a subcutaneous injection
Intervention Type
Drug
Intervention Name(s)
Chlorambucil
Other Intervention Name(s)
Leukeran
Intervention Description
Chlorambucil administered on Days 1-7 every 28 days to allow appropriate therapy for participants with CLL and to coordinate into a cycle period equivalent to other study treatment regimens.
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Other Intervention Name(s)
Revlimid
Intervention Description
Lenalidomide administered orally
Primary Outcome Measure Information:
Title
Duration of Exposure to IDELA
Description
Duration of exposure to IDELA was summarized using descriptive statistics.
Time Frame
First dose date up to 12 months
Title
Toxicity of Administration of IDELA
Description
Percentage of participants experiencing toxicities of administration of IDELA were measured according to the Common Terminology Criteria for Adverse Events v4.02
Time Frame
First dose date up to 5 years
Secondary Outcome Measure Information:
Title
Overall Response Rate
Description
Overall Response Rate (ORR) was defined as the percentage of participants achieving a complete response (CR) or partial response (PR). The response definitions were based on the following standard criteria established for each indication: CLL: International Workshop on chronic lymphocytic leukemia (IWCLL),2008 iNHL & MCL: Cheson, 2007
Time Frame
Up to 5 years
Title
Duration of Response
Description
Duration of response (DOR) was defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of disease progression or death from any cause.
Time Frame
Up to 5 years
Title
Time to Response
Description
Time to response (TTR) was defined as the interval from the start of study drug to the first documentation of CR or PR.
Time Frame
Up to 5 years
Title
Progression-free Survival
Description
Progression free survival (PFS) was defined as the interval from the start of study drug to the earlier of the first documentation of disease progression or death from any cause. The response definitions were based on the following standard criteria established for each indication: CLL: International Workshop on chronic lymphocytic leukemia (IWCLL), 2008 iNHL & MCL: Cheson, 2007
Time Frame
Up to 5 years
Title
Overall Survival
Description
Overall Survival (OS) was defined as the interval from the start of study drug to death from any cause.
Time Frame
Up to 5 years
Title
Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5)
Time Frame
Predose, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0 hours postdose at Week 0; predose, 1.5 hours postdose at Weeks 4, 12, and 24
Title
Plasma Concentration of IDELA (Cohort 4)
Time Frame
Predose at Week 0; predose, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0 hours postdose at Week 4; predose, 1.5 hours postdose at Week 12; and predose, 1.5 hours postdose at Week 24
Title
Plasma Concentration of IDELA (Cohort 6)
Time Frame
Predose, 1.5 hours postdose at Weeks 0, 4, 12 and 24
Title
Plasma Concentration of IDELA (Cohort 7)
Time Frame
Predose, 1.5 hours postdose at Weeks 0, 5 and 13
Title
Sub-study: Plasma Concentration of IDELA (Cohorts 1-4)
Time Frame
pre dose and 0.5, 1, 1.5, 2.0, 3.0, 4.0, and 6.0 hours post dose
Title
Plasma Concentration of Bendamustine
Time Frame
Predose, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0 hours postdose at Week 0
Title
Plasma Concentration of Everolimus
Time Frame
Predose, 1.5 hours postdose at Weeks 0 and 4
Title
Plasma Concentration of Lenalidomide
Time Frame
Predose, 1.5 hours postdose at Week 1 and predose at Week 5

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: Age ≥ 18 Previously treated with relapsed or refractory disease (refractory defined as not responding to a standard regimen or progressing within 6 months of the last course of a standard regimen) Disease status requirement: For CLL patients, symptomatic disease that mandates treatment as defined by the International Workshop on Chronic Lymphocytic Lymphoma (IWCLL) 2008 criteria For indolent NHL and MCL patients, measurable disease by CT scan defined as at least 1 lesion that measures > 2 cm in a single dimension WHO performance status of ≤ 2 For men and women of child-bearing potential, willing to use adequate contraception (ie, latex condom, cervical cap, diaphragm, abstinence, etc.) for the entire duration of the study. For Cohort 7 only: Women of child bearing potential must have 2 negative pregnancy tests prior to starting lenalidomide. Able to provide written informed consent Key Exclusion Criteria: Is not a good candidate to receive any of the drugs administered in the study for a given disease (idelalisib, bendamustine, rituximab, ofatumumab, fludarabine, everolimus, bortezomib, or chlorambucil), according to the clinical judgment of the investigator Patients with atypical immunophenotype with t(11:14) translocation or cyclin D1 over-expression (CLL patients only) Had radiotherapy, radioimmunotherapy, biological therapy, chemotherapy, or treatment with an investigational product within 4-weeks prior to the baseline disease status tests Had treatment with a short course of corticosteroids for symptom relief within 1-week prior to the baseline disease status tests Has had an allogeneic hematopoietic stem cell transplant Has known active central nervous system involvement of the malignancy Is pregnant or nursing Has active, serious infection requiring systemic therapy. Patients may receive prophylactic antibiotics and antiviral therapy at the discretion of the investigator Has absolute neutrophil count (ANC) < 1000/µL, unless it is related to underlying CLL, MCL or indolent NHL, the latter documented by > 50% infiltration of bone marrow by tumor cells Has platelet count < 75000/µL, unless it is related to underlying CLL, MCL, or iNHL, the latter documented by > 50% infiltration of bone marrow by tumor cells Has serum creatinine ≥ 2.0 mg/dL For Cohort 7 only: Has creatinine clearance < 60 mL/min Has serum bilirubin ≥ 2 mg/dL (unless due to Gilbert's syndrome) for patients with iNHL or CLL; for patients with MCL, serum bilirubin ≥ 1.5 x upper limit of normal Has serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≥ 2 x upper limit of normal Has Child-Pugh Class B or C hepatic impairment Has a positive test for HIV antibodies Has active hepatitis B or C (confirmed by RNA test). Patients with serologic evidence of prior exposure are eligible. Prior treatment with idelalisib Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
Clearview Cancer Institute
City
Huntsville
State/Province
Alabama
ZIP/Postal Code
35805
Country
United States
Facility Name
UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90024
Country
United States
Facility Name
Stanford Cancer Center
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304-5548
Country
United States
Facility Name
Center for Cancer and Blood Disorders
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20817
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Long Island Jewish Medical Center
City
New Hyde Park
State/Province
New York
ZIP/Postal Code
11040
Country
United States
Facility Name
Weill Medical College of Cornell
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Willamette Valley Cancer Institute and Research Center
City
Springfield
State/Province
Oregon
ZIP/Postal Code
97477
Country
United States
Facility Name
Sarah Cannon Research Institute
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
MD Anderson Cancer
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
North Star Lodge Cancer Center
City
Yakima
State/Province
Washington
ZIP/Postal Code
98902
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy.
IPD Sharing Time Frame
18 months after study completion
IPD Sharing Access Criteria
A secured external environment with username, password, and RSA code.
IPD Sharing URL
https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy
Citations:
Citation
Barrientos JC, Coutre SE, de Vos S, et al. Long-term follow-up of a Phase 1b trial of idelalisib in combination with chemoimmunotherapy in patients with relapsed/refractory chronic lymphocytic leukemia including patients with del17p/TP53 mutation. 51st Annual Meeting of the American Society of Clinical Oncology (ASCO). 29 May-02 June 2015; Chicago, IL, USA. [Poster 7011].
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Barrientos J, Coutre S, de Vos S, et al. Long-term follow-up of a Phase 1 study evaluating the selective PI3K-delta inhibitor idelalisib in combination with bendamustine (B), bendamustine/rituximab (BR), fludarabine (F), chlorambucil (Chl), Or chlorambucil/rituximab (ChlR) in patients with relapsed or refractory chronic lymphocytic leukemia. Society of Hematology (ASH) Annual Meeting. December 6-9, 2014; San Francisco, CA, USA. Poster 3343.
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de Vos S, Wagner-Johnston N, Coutre S, et al. Durable responses following treatment with the PI3K-delta inhibitor idelalisib in combination with rituximab, bendamustine, or both, in recurrent indolent non-Hodgkin lymphoma: Phase I/II results. Society of Hematology (ASH) Annual Meeting. December 6-9, 2014; San Francisco, CA, USA. Poster 3063.
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Barrientos J, Leonard J, Furman R, Flinn I, De Vos S, Coutre S, et al. Phase 1b study of idelalisib (GS-1101) plus chlorambucil ± rituximab in patients with relapsed and refractory chronic lymphocytic leukemia (CLL). European Hematology Association (EHA) 2013 Congress, 13-16 June 2013; Stockholm, Sweden. Abstract P100.
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Barrientos J, Sharman J, De Vos S, et al. GS-1101 (CAL-101), selective phosphatidylinositol 3-Kinase inhibitor, in combination with ofatumumab for treatment of relapsed/refractory chronic lymphocytic leukemia. European Hematology Association (EHA) 2012 Congress, 14-17 June 2012; Amsterdam, The Netherlands. Abstract 1062.
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Coutre S, Leonard J, Furman R, et al. Combinations of the selective phosphatidylinositol 3 Kinase-delta (PI3Kd) inhibitor GS-1101 (CAL-101) with rituximab and/or bendamustine are tolerable and highly active in patients with relapsed or refractory chronic lymphocytic leukemia (CLL): results from a phase 1 study. American Society of Hematology (ASH) Annual Meeting. 8-11 December 2012; Atlanta, GA, USA. Abstract 642.
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de Vos S, Schreeder M, Finn I, et al. A phase 1 study of the selective phosphatidylinositol 3 Kinase-delta (PI3Kd) inhibitor CAL-101 (GS-1101) in combination with rituximab and/or bendamustine in patients with relapsed or refractory indolent non-Hodgkin lymphoma (iNHL). American Society of Hematology (ASH) 2011 Annual Meeting, 10-13 December 2011; San Diego, CA, USA. Abstract 2699.
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Flinn I, Schreeder M, Wagner-Johnson N, et al. A phase 1 study of CAL-101, an isoform-selective inhibitor of phosphatidylinositol 3-Kinase P110δ, in combination with rituximab and/or bendamustine in patients with relapsed or refractory B-cell malignancies. American Society of Hematology (ASH) 2010 Annual Meeting, 04-07 December 2010; Orlando, FL, USA. Blood (ASH Annual Meeting Abstracts) 2010 116: Abstract 2832.
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Flinn I, Schreeder M, Coutre S, et al. A phase 1 study of CAL-101, an isoform-selective inhibitor of phosphatidylinositol 3-Kinase P110δ, in combination with anti-CD20 monoclonal antibody therapy and/or bendamustine in patients with previously treated B-cell malignancies. 47th Annual Meeting of the American Society of Clinical Oncology (ASCO). 04-08 June 2011; Chicago, IL, USA. [Poster 3064].
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Fowler N, de Vos S, Schreeder M, et al. Combinations of the phosphatidylinositol 3 Kinase delta (PI3Kd) inhibitor idelalisib (GS-1101) with rituximab and/or bendamustine are tolerable and highly active in previously treated, indolent non-Hodgkin lymphoma: results from a phase 1 study. American Society of Hematology (ASH) 2012.
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Furman R, Barrientos J, Sharman J, et al. A phase 1/2 study of the selective phosphatidylinositol 3-Kinase-delta (PI3Kd) inhibitor CAL-101 (GS-1101) with ofatumumab in patients with previously treated chronic lymphocytic leukemia (CLL). [Poster 6518] 2012 American Society of Clinical Oncology (ASCO) Annual Meeting; 01 05 June, 2012; Chicago, IL, USA. Gilead Sciences, Inc. [Poster 6518].
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Sharman J, de Vos S, Leonard J, et al. A phase 1 study of the selective phosphatidylinositol 3-Kinase-delta (PI3Kd) inhibitor CAL-101 (GS-1101) in combination with rituximab and/or bendamustine in patients with relapsed or refractory chronic lymphocytic leukemia. American Society of Hematology (ASH) 2011 Annual Meeting, 10-13 December 2011; San Diego, CA, USA. Abstract 1787.
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Wagner-Johnston ND, De Vos S, Leonard J, Sharman JP, Schreeder MT, Boccia RV, et al. Preliminary results of PI3Kδ inhibitor idelalisib (GS-1101) treatment in combination with everolimus, bortezomib, or bendamustine/rituximab in patients with previously treated mantle cell lymphoma (MCL) [Abstract 8501]. J Clin Oncol (ASCO Annual Meeting Abstracts) 2013;31 (suppl).
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Learn more about this trial

Study to Investigate Idelalisib in Combination With Chemotherapeutic Agents, Immunomodulatory Agents and Anti-CD20 Monoclonal Antibody (mAb) in Participants With Relapsed or Refractory Indolent B-cell Non-Hodgkin's Lymphoma, Mantle Cell Lymphoma or Chronic Lymphocytic Leukemia

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