Ibrutinib Plus Venetoclax in Subjects With Treatment-naive Chronic Lymphocytic Leukemia /Small Lymphocytic Lymphoma (CLL/SLL) (Captivate)

Pharmacyclics

Status and phase: Completed; Phase 2

Conditions: Small Lymphocytic Lymphoma; Chronic Lymphocytic Leukemia; Leukemia

Treatments: Drug: venetoclax; Drug: ibrutinib; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02910583

2016-002293-12 (EudraCT Number)

PCYC-1142-CA

Details and patient eligibility

About

This is a multicenter, 2-cohort Phase 2 study assessing both minimal residual disease (MRD)-guided discontinuation and fixed duration therapy with the combination of ibrutinib + venetoclax in subjects with treatment-naïve CLL or SLL.

Enrollment: 323 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of CLL/SLL that meets 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) diagnostic criteria (Hallek et al), with active disease meeting at least 1 IWCLL criteria for requiring treatment.
• Measurable nodal disease by computed tomography (CT)
• Adequate hepatic, and renal function
• Adequate hematologic function
• absolute neutrophil count >750/µL
• platelet count >30,000 /μL
• hemoglobin >8.0 g/dL

Exclusion criteria

• Any prior therapy used for treatment of CLL/SLL
• Known allergy to xanthine oxidase inhibitors and/or rasburicase for subjects at risk for tumor lysis syndrome (TLS)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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323 participants in 5 patient groups, including a placebo group

Fixed Duration (FD) Cohort: Open Label Ibrutinib + Venetoclax

Experimental group

Description:

Participants receive 420 mg of single-agent ibrutinib for first 3 cycles followed by ibrutinib plus venetoclax combination treatment (ibrutinib 420 mg and venetoclax 400 mg orally once daily on a continuous schedule) for 12 cycles (a cycle is defined by 28 days) or until disease progression or unacceptable toxicity.

Treatment:

Drug: ibrutinib

Drug: venetoclax

MRD Cohort/Confirmed Undetectable MRD (uMRD): Randomized to Ibrutinib (Blinded)

Experimental group

Description:

Participants receive 420 mg of single-agent ibrutinib for the first 3 cycles followed by ibrutinib plus venetoclax combination treatment for at least 12 cycles (a cycle is defined as 28 days) prior to randomization (pre-randomization phase). Participants with confirmed uMRD are randomized to receive ibrutinib 420 mg orally once daily on a continuous schedule until MRD-positive relapse, disease progression (PD), or unacceptable toxicity. After MRD-positive relapse or disease progression (PD) by iwCLL criteria, participants can reintroduce 400 mg venetoclax with a 5-week ramp up. If venetoclax is to be reintroduced, venetoclax treatment is to continue at the dose of 400 mg/day for up to approximately 2 years (cumulative) until PD or unacceptable toxicity.

Treatment:

Drug: ibrutinib

Drug: venetoclax

MRD Cohort/Confirmed uMRD: Randomized Placebo (Blinded)

Placebo Comparator group

Description:

Participants receive 420 mg of single-agent ibrutinib for the first 3 cycles followed by ibrutinib plus venetoclax combination treatment for at least 12 cycles (a cycle is defined as 28 days) prior to randomization (pre-randomization phase). Participants with confirmed uMRD are randomized to receive placebo orally once daily on a continuous schedule until MRD-positive relapse, PD or unacceptable toxicity. If MRD-positive relapse or PD is confirmed after restaging per iwCLL criteria, participants can first reintroduce oral daily ibrutinib with the option of subsequently reintroducing 400 mg venetoclax with a 5-week ramp up, if subsequent disease relapse per iwCLL criteria occurs after ibrutinib reintroduction. If venetoclax is to be reintroduced, venetoclax treatment is to continue at the dose of 400 mg/day for up to approximately 2 years (cumulative) until PD or unacceptable toxicity.

Treatment:

Drug: ibrutinib

Drug: venetoclax

Drug: Placebo

MRD Cohort/uMRD Not Confirmed: Randomized to Ibrutinib (Open-Label)

Experimental group

Description:

Participants receive 420 mg of single-agent ibrutinib for the first 3 cycles followed by ibrutinib plus venetoclax combination treatment for at least 12 cycles (a cycle is defined as 28 days) prior to randomization (pre randomization phase). Participants with uMRD not confirmed are randomized to receive open-label ibrutinib 420 mg orally once daily on a continuous schedule until PD or unacceptable toxicity. In case of confirmed PD after restaging per iwCLL criteria, participants can continue ibrutinib and reintroduce venetoclax treatment. If venetoclax is to be reintroduced, venetoclax treatment is to continue at the dose of 400 mg/day for up to approximately 2 years (cumulative) until PD or unacceptable toxicity.

Treatment:

Drug: ibrutinib

Drug: venetoclax

MRD Cohort/uMRD Not Confirmed: Randomized Ibrutinib + Venetoclax (Open-Label)

Experimental group

Description:

Participants receive 420 mg of single-agent ibrutinib for the first 3 cycles followed by ibrutinib plus venetoclax combination treatment for at least 12 cycles (a cycle is defined as 28 days) prior to randomization (pre randomization phase). Participants with uMRD not confirmed are randomized to receive open-label ibrutinib 420 mg and venetoclax 400 mg orally once daily on a continuous schedule until PD or unacceptable toxicity. Venetoclax was allowed for administration up to 2 years cumulatively from first dose started in the pre-randomization phase to last dose in the randomization phase.

Treatment:

Drug: ibrutinib

Drug: venetoclax