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

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ClinicalTrials.gov Identifier: NCT03112174
Recruitment Status : Recruiting
First Posted : April 13, 2017
Last Update Posted : October 9, 2020
Sponsor:
Collaborator:
Janssen Research & Development, LLC
Information provided by (Responsible Party):
Pharmacyclics LLC.

Tracking Information
First Submitted Date  ICMJE April 4, 2017
First Posted Date  ICMJE April 13, 2017
Last Update Posted Date October 9, 2020
Actual Study Start Date  ICMJE May 12, 2017
Estimated Primary Completion Date March 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 26, 2019)
  • Occurrence of Tumor Lysis Syndrome (TLS) [ Time Frame: Approximately 3 months after last subject enrolled into safety run-in portion ]
    To evaluate the occurrence of tumor lysis syndrome (TLS) with the concurrent administration of ibrutinib and venetoclax.
  • Occurrence of Dose Limiting Toxicities (DLT) [ Time Frame: Approximately 3 months after last subject enrolled into safety run-in portion ]
    To evaluate the occurrence of DLTs with the concurrent administration of ibrutinib and venetoclax.
  • Progression-free Survival (PFS) [ Time Frame: approximately 1 year after last subject has stopped treatment with study drug(s) ]
    To evaluate PFS of ibrutinib and venetoclax compared to ibrutinib and placebo.
  • Complete Response (CR) [ Time Frame: approximately 1 year after last subject has stopped treatment with study drug(s) ]
    To evaluate the complete response (CR) rate with the combination of ibrutinib and venetoclax in subjects with treatment-naive MCL
Original Primary Outcome Measures  ICMJE
 (submitted: April 7, 2017)
  • Occurrence of Tumor Lysis Syndrome (TLS) [ Time Frame: Approximately 3 months after last subject enrolled into safety run-in portion ]
    To evaluate the occurrence of tumor lysis syndrome (TLS) with the concurrent administration of ibrutinib and venetoclax.
  • Occurrence of Dose Limiting Toxicities (DLT) [ Time Frame: Approximately 3 months after last subject enrolled into safety run-in portion ]
    To evaluate the occurrence of DLTs with the concurrent administration of ibrutinib and venetoclax.
  • Progression-free Survival (PFS) [ Time Frame: approximately 1 year after last subject has stopped treatment with study drug(s) ]
    To evaluate PFS of ibrutinib and venetoclax compared to ibrutinib and placebo.
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Ibrutinib Combined With Venetoclax in Subjects With Mantle Cell Lymphoma (SYMPATICO)
Official Title  ICMJE Phase 3 Study of Ibrutinib in Combination With Venetoclax in Subjects With Mantle Cell Lymphoma
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Mantle-Cell Lymphoma
Intervention  ICMJE
  • Drug: Ibrutinib
    Administered orally once daily
  • Drug: Venetoclax
    Administered orally once daily
  • Drug: Placebo Oral tablet to match Venetoclax
    Administered orally once daily
Study Arms  ICMJE
  • Experimental: Safety Run-in Period

    Subjects 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.

    Interventions:
    • Drug: Ibrutinib
    • Drug: Venetoclax
  • Experimental: Phase 3: Ibrutinb + Venetoclax
    Subjects will be randomized to receive ibrutinib and venetoclax/placebo until clinical disease progression or unacceptable toxicity
    Interventions:
    • Drug: Ibrutinib
    • Drug: Venetoclax
  • Placebo Comparator: Phase 3: Ibrutinib + Placebo
    Subjects will be randomized to receive ibrutinib and venetoclax/placebo until clinical disease progression or unacceptable toxicity
    Interventions:
    • Drug: Ibrutinib
    • Drug: Placebo Oral tablet to match Venetoclax
  • Experimental: Treatment-naive

    This 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.

    Interventions:
    • Drug: Ibrutinib
    • Drug: Venetoclax
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 26, 2019)
362
Original Estimated Enrollment  ICMJE
 (submitted: April 7, 2017)
287
Estimated Study Completion Date  ICMJE September 2022
Estimated Primary Completion Date March 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Brandon Bishop +1-855-427-8846 medinfo@pcyc.com
Listed Location Countries  ICMJE Australia,   Belgium,   Canada,   Czechia,   France,   Germany,   Greece,   Hungary,   Italy,   Korea, Republic of,   Netherlands,   Poland,   Spain,   Turkey,   Ukraine,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03112174
Other Study ID Numbers  ICMJE PCYC-1143-CA
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pharmacyclics LLC.
Study Sponsor  ICMJE Pharmacyclics LLC.
Collaborators  ICMJE Janssen Research & Development, LLC
Investigators  ICMJE Not Provided
PRS Account Pharmacyclics LLC.
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP