Efficacy and Safety of Idelalisib in Combination With Obinutuzumab Compared to Chlorambucil in Combination With Obinutuzumab for Previously Untreated Chronic Lymphocytic Leukemia

Gilead Sciences

Status and phase: Terminated; Phase 3

Conditions: Chronic Lymphocytic Leukemia

Treatments: Drug: Chlorambucil; Drug: Obinutuzumab; Drug: Idelalisib

Study type: Interventional

Funder types: Industry

Identifiers

NCT01980875

GS-US-312-0118

2013-004551-20 (EudraCT Number)

Details and patient eligibility

About

The primary objective of this study is to evaluate the effects of idelalisib with obinutuzumab versus the combination of chlorambucil and obinutuzumab on progression-free survival (PFS) in participants with previously untreated chronic lymphocytic leukemia (CLL).

An increased rate of deaths and serious adverse events (SAEs) among participants with front-line CLL and early-line indolent non-Hodgkin lymphoma (iNHL) treated with idelalisib in combination with standard therapies was observed by the independent data monitoring committee (DMC) during regular review of 3 Gilead Phase 3 studies. Gilead reviewed the unblinded data and terminated those studies in agreement with the DMC recommendation and in consultation with the US Food and Drug Administration (FDA). All front-line studies of idelalisib, including this study, were also terminated.

Enrollment: 57 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Not a candidate for fludarabine therapy based on either:

  1. creatinine clearance < 70 mL/min, or
  2. Cumulative Illness Rating Scale score > 6, by assessment of the investigator

• Diagnosis of B-cell CLL, with diagnosis established according to International Workshop on Chronic Lymphocytic Leukemia (IWCLL)

• No prior therapy for CLL other than corticosteroids for disease complications.

• CLL that warrants treatment

• Presence of measurable lymphadenopathy

• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2

Key Exclusion Criteria:

• Known histological transformation from CLL to an aggressive lymphoma (ie, Richter transformation)
• Known presence of myelodysplastic syndrome
• Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of randomization
• Ongoing liver injury
• Ongoing drug-induced pneumonitis
• Ongoing inflammatory bowel disease
• History of prior allogeneic bone marrow progenitor cell or solid organ transplantation
• Ongoing immunosuppressive therapy other than corticosteroids
• Concurrent participation in another therapeutic clinical trial
• Undergone major surgery within 30 days prior to randomization
• Known hypersensitivity or intolerance to any of the active substances or excipients in the formulations for idelalisib, obinutuzumab, or chlorambucil
• History of non-infectious pneumonitis
• Received last dose of study drug on another therapeutic clinical trial within 30 days prior to randomization

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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57 participants in 3 patient groups

Safety Run-In: Idelalisib+obinutuzumab

Experimental group

Description:

Participants will receive idelalisib for 96 weeks and obinutuzumab over 21 weeks. Following 4 weeks of treatment, safety data will be reviewed by an independent data monitoring committee (DMC). If acceptable tolerability is observed, the randomized portion of the study will begin.

Treatment:

Drug: Obinutuzumab

Drug: Idelalisib

Randomized: Idelalisib+obinutuzumab

Experimental group

Description:

Participants will receive idelalisib for 96 weeks and obinutuzumab over 21 weeks.

Treatment:

Drug: Obinutuzumab

Drug: Idelalisib

Randomized: Obinutuzumab+chlorambucil

Active Comparator group

Description:

Participants will receive obinutuzumab over 21 weeks and chlorambucil over 23 weeks.

Treatment:

Drug: Obinutuzumab

Drug: Chlorambucil