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

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ClinicalTrials.gov Identifier: NCT02910583
Recruitment Status : Active, not recruiting
First Posted : September 22, 2016
Last Update Posted : September 26, 2018
Sponsor:
Collaborator:
Janssen Research & Development, LLC
Information provided by (Responsible Party):
Pharmacyclics LLC.

Brief Summary:
This is a multicenter, 2-cohort Phase 2 study assessing both MRD-guided discontinuation and fixed duration therapy with the combination of ibrutinib + venetoclax in subjects with treatment-naïve CLL or SLL

Condition or disease Intervention/treatment Phase
Leukemia, Chronic Lymphocytic Lymphoma, Small Lymphocytic Drug: ibrutinib Drug: placebo to match ibrutinib Drug: venetoclax Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 289 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase 2 Study of the Combination of Ibrutinib Plus Venetoclax in Subjects With Treatment-naïve Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Study Start Date : October 2016
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020


Arm Intervention/treatment
Experimental: MRD Cohort Randomized ibrutinib (blinded)
Subjects will receive 420 mg capsules of single-agent ibrutinib for the first 3 cycles followed by ibrunitib plus venetoclax combination treatment for at least 12 cycles (a cycle is defined as 28 days) prior to randomization. Subjects that are MRD-negative will be randomized to receive ibrutinib 420 mg capsules orally once daily on a continuous schedule until clinical disease progression or unacceptable toxicity
Drug: ibrutinib
ibrutinib 420mg capsules administered orally once daily

Drug: venetoclax
venetoclax tablets will be administered orally once daily starting with a 5 week ramp up of 20 mg, 50 mg, 100 mg, 200 mg and 400 mg. After ramp up, venetoclax will be administered at 400 mg.

Placebo Comparator: MRD Cohort Randomized Placebo to match ibrutinib (blinded)
Subjects will receive 420 mg capsules 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. Subjects that are MRD-negative will be randomized to receive matching ibrutinib placebo capsules orally once daily on a continuous schedule until MRD-positive relapse, clinical disease progression or unacceptable toxicity.
Drug: ibrutinib
ibrutinib 420mg capsules administered orally once daily

Drug: placebo to match ibrutinib
placebo capsules to match ibrutinib administered orally once daily

Drug: venetoclax
venetoclax tablets will be administered orally once daily starting with a 5 week ramp up of 20 mg, 50 mg, 100 mg, 200 mg and 400 mg. After ramp up, venetoclax will be administered at 400 mg.

Experimental: MRD Cohort Randomized open-label ibrutinib + venetoclax
Subjects will receive 420 mg capsules of single-agent ibrutinib for the first 3 cycles followed by ibrunitib plus venetoclax combination treatment for at least 12 cycles (a cycle is defined as 28 days) prior to randomization. Subjects that are MRD-positive will be randomized to receive ibrutinib 420 mg capsules and venetoclax 400 mg tablets orally once daily on a continuous schedule until clinical disease progression or unacceptable toxicity.
Drug: ibrutinib
ibrutinib 420mg capsules administered orally once daily

Drug: venetoclax
venetoclax tablets will be administered orally once daily starting with a 5 week ramp up of 20 mg, 50 mg, 100 mg, 200 mg and 400 mg. After ramp up, venetoclax will be administered at 400 mg.

Experimental: MRD Cohort Randomized open-label ibrutinib
Subjects will receive 420 mg capsules of single-agent ibrutinib for the first 3 cycles followed by ibrunitib plus venetoclax combination treatment for at least 12 cycles (a cycle is defined as 28 days) prior to randomization. Subjects that are MRD-positive will be randomized to receive ibrutinib 420 mg capsules orally once daily on a continuous scheduled until clinical disease progression or unacceptable toxicity.
Drug: ibrutinib
ibrutinib 420mg capsules administered orally once daily

Drug: venetoclax
venetoclax tablets will be administered orally once daily starting with a 5 week ramp up of 20 mg, 50 mg, 100 mg, 200 mg and 400 mg. After ramp up, venetoclax will be administered at 400 mg.

Experimental: Fixed Duration Cohort - Open Label ibrutinib + venetoclax
Subjects will receive 420 mg capsules of single agent ibrutinib for first 3 cycles followed by ibrutinib plus venetoclax combination treatment for 12 cycles (a cycle is defined by 28 days) or until disease progression or unacceptable toxicity.
Drug: ibrutinib
ibrutinib 420mg capsules administered orally once daily

Drug: venetoclax
venetoclax tablets will be administered orally once daily starting with a 5 week ramp up of 20 mg, 50 mg, 100 mg, 200 mg and 400 mg. After ramp up, venetoclax will be administered at 400 mg.




Primary Outcome Measures :
  1. MRD-negative response rate [ Time Frame: approximately 40 months ]
  2. Disease free survival [ Time Frame: approximately 40 months ]
  3. Complete Response Rate [ Time Frame: approximately 24 months ]


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of CLL/SLL that meets IWCLL diagnostic criteria (Hallek 2008), 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 TLS

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02910583


  Show 40 Study Locations
Sponsors and Collaborators
Pharmacyclics LLC.
Janssen Research & Development, LLC
Investigators
Study Director: Joi Ninomoto, PharmD Pharmacyclics LLC.
Study Director: Jim Dean, MD, PhD Pharmacyclics LLC.

Responsible Party: Pharmacyclics LLC.
ClinicalTrials.gov Identifier: NCT02910583     History of Changes
Other Study ID Numbers: PCYC-1142-CA
First Posted: September 22, 2016    Key Record Dates
Last Update Posted: September 26, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Lymphoma
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Venetoclax
Antineoplastic Agents