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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03112174




Registration number
NCT03112174
Ethics application status
Date submitted
4/04/2017
Date registered
13/04/2017
Date last updated
26/06/2020

Titles & IDs
Public title
Study of Ibrutinib Combined With Venetoclax in Subjects With Mantle Cell Lymphoma (SYMPATICO)
Scientific title
Phase 3 Study of Ibrutinib in Combination With Venetoclax in Subjects With Mantle Cell Lymphoma
Secondary ID [1] 0 0
PCYC-1143-CA
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mantle-Cell Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ibrutinib
Treatment: Drugs - Venetoclax
Treatment: Drugs - Placebo Oral tablet to match Venetoclax

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.

Experimental: Phase 3: Ibrutinb + Venetoclax - Subjects will be randomized to receive ibrutinib and venetoclax/placebo until clinical disease progression or unacceptable toxicity

Placebo Comparator: Phase 3: Ibrutinib + Placebo - Subjects will be randomized to receive ibrutinib and venetoclax/placebo until clinical disease progression or unacceptable toxicity

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.


Treatment: Drugs: Ibrutinib
Administered orally once daily

Treatment: Drugs: Venetoclax
Administered orally once daily

Treatment: Drugs: Placebo Oral tablet to match Venetoclax
Administered orally once daily

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Occurrence of Tumor Lysis Syndrome (TLS) - To evaluate the occurrence of tumor lysis syndrome (TLS) with the concurrent administration of ibrutinib and venetoclax.
Timepoint [1] 0 0
Approximately 3 months after last subject enrolled into safety run-in portion
Primary outcome [2] 0 0
Occurrence of Dose Limiting Toxicities (DLT) - To evaluate the occurrence of DLTs with the concurrent administration of ibrutinib and venetoclax.
Timepoint [2] 0 0
Approximately 3 months after last subject enrolled into safety run-in portion
Primary outcome [3] 0 0
Progression-free Survival (PFS) - To evaluate PFS of ibrutinib and venetoclax compared to ibrutinib and placebo.
Timepoint [3] 0 0
approximately 1 year after last subject has stopped treatment with study drug(s)
Primary outcome [4] 0 0
Complete Response (CR) - To evaluate the complete response (CR) rate with the combination of ibrutinib and venetoclax in subjects with treatment-naive MCL
Timepoint [4] 0 0
approximately 1 year after last subject has stopped treatment with study drug(s)

Eligibility
Key inclusion criteria
Relapsed/Refractory Arm



- 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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



- 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
The Canberra Hospital - Canberra
Recruitment hospital [2] 0 0
Border Medical Oncology Research Unit - Albury
Recruitment hospital [3] 0 0
Icon Cancer Care - Auchenflower
Recruitment hospital [4] 0 0
Austin Health - Heidelberg
Recruitment hospital [5] 0 0
Peter MacCallum Cancer - Melbourne
Recruitment hospital [6] 0 0
St.Vincent's Hospital - Melbourne
Recruitment hospital [7] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
2605 - Canberra
Recruitment postcode(s) [2] 0 0
2640 - Albury
Recruitment postcode(s) [3] 0 0
4101 - Auchenflower
Recruitment postcode(s) [4] 0 0
3084 - Heidelberg
Recruitment postcode(s) [5] 0 0
3000 - Melbourne
Recruitment postcode(s) [6] 0 0
3065 - Melbourne
Recruitment postcode(s) [7] 0 0
6009 - Nedlands
Recruitment outside Australia
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Pharmacyclics LLC.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Janssen Research & Development, LLC
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03112174
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Brandon Bishop
Address 0 0
Country 0 0
Phone 0 0
+1-855-427-8846
Fax 0 0
Email 0 0
medinfo@pcyc.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03112174