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 : February 26, 2021
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Mantle-Cell Lymphoma | Drug: Ibrutinib Drug: Venetoclax Drug: Placebo Oral tablet to match Venetoclax | Phase 3 |
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 |
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 |
- 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

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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

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
Contact: Brandon Bishop | +1-855-427-8846 | medinfo@pcyc.com |

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: | February 26, 2021 |
Last Verified: | February 2021 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
PCYC MCL Non-Hodgkin's Lymphoma NHL |
ibrutinib venetoclax Pharmacyclics |
Lymphoma Lymphoma, Mantle-Cell Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases |
Immunoproliferative Disorders Immune System Diseases Lymphoma, Non-Hodgkin Venetoclax Antineoplastic Agents |