Clinical Trials /

Study of Ibrutinib Combined With Venetoclax in Subjects With Mantle Cell Lymphoma (SYMPATICO)

NCT03112174

Description:

This Phase 3 multinational, randomized, double-blind study is designed to compare the efficacy and safety of the combination of ibrutinib and venetoclax vs. ibrutinib and placebo in subjects with MCL.

Related Conditions:
  • Mantle Cell Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Study of Ibrutinib Combined With Venetoclax in Subjects With Mantle Cell Lymphoma (SYMPATICO)
  • Official Title: Phase 3 Study of Ibrutinib in Combination With Venetoclax in Subjects With Mantle Cell Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: PCYC-1143-CA
  • NCT ID: NCT03112174

Conditions

  • Mantle-Cell Lymphoma

Interventions

DrugSynonymsArms
IbrutinibPhase 3: Ibrutinb + Venetoclax
VenetoclaxPhase 3: Ibrutinb + Venetoclax
Placebo Oral tablet to match VenetoclaxPhase 3: Ibrutinib + Placebo

Purpose

This Phase 3 multinational, randomized, double-blind study is designed to compare the efficacy and safety of the combination of ibrutinib and venetoclax vs. ibrutinib and placebo in subjects with MCL.

Trial Arms

NameTypeDescriptionInterventions
Safety Run-in PeriodExperimentalSubjects are enrolled into the open-label Safety Run-in Period to evaluate the occurrence of tumor lysis syndrome (TLS) and DLTs with the concurrent administration of ibrutinib and venetoclax. Safety run-in phase for the study is closed to further enrollment as of 07-Nov-2018.
  • Ibrutinib
  • Venetoclax
Phase 3: Ibrutinb + VenetoclaxExperimentalSubjects will be randomized to receive ibrutinib and venetoclax/placebo until clinical disease progression or unacceptable toxicity
  • Ibrutinib
  • Venetoclax
Phase 3: Ibrutinib + PlaceboPlacebo ComparatorSubjects will be randomized to receive ibrutinib and venetoclax/placebo until clinical disease progression or unacceptable toxicity
  • Ibrutinib
  • Placebo Oral tablet to match Venetoclax
Treatment-naiveExperimentalThis open-label arm is designed to explore the efficacy and safety of the combination of ibrutinib and venetoclax in subjects with treatment-naive MCL. Approximately 75 subjects (of which ~25 subjects with TP53 mutation) will be enrolled and treated with ibrutinib and venetoclax.
  • Ibrutinib
  • Venetoclax

Eligibility Criteria

        Relapsed/Refractory Arm

        Inclusion Criteria:

          -  Pathologically confirmed MCL (in tumor tissue), with documentation of either
             overexpression of cyclin D1 in association with other relevant markers (eg, CD19,
             CD20, PAX5, CD5) or evidence of t(11;14) as assessed by cytogenetics, fluorescent in
             situ hybridization (FISH), or polymerase chain reaction (PCR)

          -  At least 1 measurable site of disease on cross-sectional imaging (CT/PET)

          -  At least 1, but no more than 5, prior treatment regimens for MCL

          -  Failure to achieve at least partial response (PR) with, or documented disease
             progression after, the most recent treatment regimen

          -  Subjects must have adequate fresh or paraffin embedded tissue

        Exclusion Criteria:

          -  History or current evidence of central nervous system lymphoma

          -  Concurrent enrollment in another therapeutic investigational study or prior therapy
             with ibrutinib or other BTK inhibitors

          -  Prior treatment with venetoclax or other BCL2 inhibitors

        Treatment Naïve Arm

        Inclusion Criteria:

          -  ≥65 years of age, or <65 years of age with a TP53 mutation

          -  Eastern Cooperative Oncology Group (ECOG) performance status score 0-2

          -  Adequate hematologic, hepatic, and renal function

          -  Pathologically confirmed treatment-naïve MCL

          -  At least 1 measurable site of disease

        Exclusion Criteria:

          -  Blastoid variant of MCL

          -  History or current evidence of CNS lymphoma

          -  Concurrent enrollment in another therapeutic investigational study or prior therapy
             including ibrutinib or other BTK inhibitors

          -  Prior treatment with venetoclax or other BCL2 inhibitors

          -  History of stroke or intracranial hemorrhage within 6 months prior to enrollment

          -  History of HIV or active HCV or HBV

          -  Currently active, clinically significant cardiovascular disease; or a history of
             myocardial infarction, unstable angina, or acute coronary syndrome within 6 months
             prior to randomization
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Occurrence of Tumor Lysis Syndrome (TLS)
Time Frame:Approximately 3 months after last subject enrolled into safety run-in portion
Safety Issue:
Description:To evaluate the occurrence of tumor lysis syndrome (TLS) with the concurrent administration of ibrutinib and venetoclax.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Pharmacyclics LLC.

Trial Keywords

  • PCYC
  • MCL
  • Non-Hodgkin's Lymphoma
  • NHL
  • ibrutinib
  • venetoclax
  • Pharmacyclics

Last Updated

February 28, 2020