Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03112174
Recruitment Status : Recruiting
First Posted : April 13, 2017
Last Update Posted : April 3, 2020
Sponsor:
Collaborator:
Janssen Research & Development, LLC
Information provided by (Responsible Party):
Pharmacyclics LLC.

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.

Condition or disease Intervention/treatment Phase
Mantle-Cell Lymphoma Drug: Ibrutinib Drug: Venetoclax Drug: Placebo Oral tablet to match Venetoclax Phase 3

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 362 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase 3 Study of Ibrutinib in Combination With Venetoclax in Subjects With Mantle Cell Lymphoma
Actual Study Start Date : May 12, 2017
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : September 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
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.

 Drug: Ibrutinib
Administered orally once daily

Drug: Venetoclax
Administered orally once daily
Experimental: Phase 3: Ibrutinb + Venetoclax
Subjects will be randomized to receive ibrutinib and venetoclax/placebo until clinical disease progression or unacceptable toxicity
 Drug: Ibrutinib
Administered orally once daily

Drug: Venetoclax
Administered orally once daily
Placebo Comparator: Phase 3: Ibrutinib + Placebo
Subjects will be randomized to receive ibrutinib and venetoclax/placebo until clinical disease progression or unacceptable toxicity
 Drug: Ibrutinib
Administered orally once daily

Drug: Placebo Oral tablet to match Venetoclax
Administered orally once daily
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.

 Drug: Ibrutinib
Administered orally once daily

Drug: Venetoclax
Administered orally once daily


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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): NCT03112174


Contacts
Layout table for location contacts
Contact: Brandon Bishop +1-855-427-8846 medinfo@pcyc.com

Locations
Show Show 134 study locations
Sponsors and Collaborators
Pharmacyclics LLC.
Janssen Research & Development, LLC
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for additonal information
Responsible Party: Pharmacyclics LLC.
ClinicalTrials.gov Identifier: NCT03112174    
Other Study ID Numbers: PCYC-1143-CA
First Posted: April 13, 2017    Key Record Dates
Last Update Posted: April 3, 2020
Last Verified: April 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pharmacyclics LLC.:
PCYC
MCL
Non-Hodgkin's Lymphoma
NHL
 ibrutinib
venetoclax
Pharmacyclics
Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
 Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Venetoclax
Antineoplastic Agents