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

Gilead Sciences

Status and phase: Completed; Phase 1

Conditions: Mantle Cell Lymphoma; Chronic Lymphocytic Leukemia; Indolent Non-Hodgkin's Lymphoma

Treatments: Drug: Bendamustine; Drug: Everolimus; Drug: Bortezomib; Drug: Ofatumumab; Drug: Idelalisib; Drug: Fludarabine; Drug: Rituximab; Drug: Chlorambucil; Drug: Lenalidomide

Study type: Interventional

Funder types: Industry

Identifiers

NCT01088048

101-07

Details and patient eligibility

About

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).

Enrollment: 241 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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241 participants in 10 patient groups

Idelalisib + Rituximab

Experimental group

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

Treatment:

Drug: Rituximab

Drug: Idelalisib

Idelalisib + Rituximab + Bendamustine

Experimental group

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

Treatment:

Drug: Rituximab

Drug: Idelalisib

Drug: Bendamustine

Idelalisib + Bendamustine

Experimental group

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

Treatment:

Drug: Idelalisib

Drug: Bendamustine

Idelalisib + Ofatumumab

Experimental group

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))

Treatment:

Drug: Ofatumumab

Drug: Idelalisib

Idelalisib + Fludarabine

Experimental group

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

Treatment:

Drug: Fludarabine

Drug: Idelalisib

Idelalisib + Everolimus

Experimental group

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

Treatment:

Drug: Idelalisib

Drug: Everolimus

Idelalisib + Bortezomib

Experimental group

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

Treatment:

Drug: Idelalisib

Drug: Bortezomib

Idelalisib + Chlorambucil

Experimental group

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

Treatment:

Drug: Chlorambucil

Drug: Idelalisib

Idelalisib + Rituximab + Chlorambucil

Experimental group

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

Treatment:

Drug: Chlorambucil

Drug: Rituximab

Drug: Idelalisib

Idelalisib + Rituximab + Lenalidomide

Experimental group

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

Treatment:

Drug: Lenalidomide

Drug: Rituximab

Drug: Idelalisib