Clinical trial NCT01088048
Conditions: Indolent Non-Hodgkin's Lymphoma Chronic Lymphocytic Leukemia Mantle Cell Lymphoma
Keywords: phosphatidylinositol 3-kinase Ofatumumab indolent non-Hodgkin lymphoma (iNHL)
Sponsor: Gilead Sciences
Start date: 2010-03-25; Completion date: 2015-04-28
Enrollment: 241 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

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).

Detailed description:

Arms: arm 1: 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 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 arm 3: 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 4: 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 5: 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 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 arm 7: 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 8: 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 9: 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 10: 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
Interventions: intervention 1: Idelalisib intervention 2: Rituximab intervention 3: Bendamustine intervention 4: Ofatumumab intervention 5: Fludarabine intervention 6: Everolimus intervention 7: Bortezomib intervention 8: Chlorambucil intervention 9: Lenalidomide
Intervention descriptions: intervention 1: Idelalisib tablet administered orally intervention 2: Rituximab administered intravenously intervention 3: Bendamustine administered intravenously intervention 4: Ofatumumab administered intravenously intervention 5: Fludarabine administered orally intervention 6: Everolimus administered orally twice daily until disease progression intervention 7: Bortezomib administered as a subcutaneous injection intervention 8: 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 9: Lenalidomide administered orally

Protocol documents: