CC486-CHOP in Patients With Previously Untreated Peripheral T-cell Lymphoma

Study Overview
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Brief Summary
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This is a phase II, multi-center study to determine the efficacy and safety of first-line CC-486 plus CHOP in patients with PTCL who have received no prior systemic therapy. The study has a sample size of 20, and follows two-stage minimax design for primary efficacy analysis.

Detailed Description
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Study Summary: This is a phase II, multi-center study to determine the efficacy and safety of first-line CC-486 plus CHOP in patients with Peripheral T-cell Lymphoma (PTCL) who have received no prior systemic therapy. The main objective is to determine the complete response rate (CR) of CC486-CHOP in PTCL. CR rate after cycle 6 will be used for the purpose of interim efficacy analysis. The study includes 6 cycles ( 18 weeks) of treatment and 2 years of follow-up. The projected end date is 12/31/2022. Patients achieving complete remission will be evaluated every 6 months for 2 years or until disease progression. Patients who have disease progression will be contacted every 6 months to assess for survival status. Standard dose CHOP will be provided on day 1 of each cycle and repeat every 3 weeks for a total of 6 cycles. CC486 at 300 mg daily will be administered orally from day -6 to day 0 for cycle 1 priming, and on days 8-21 following cycles 1-5. Patients in CR/PR following 6 cycles of treatment have the option to proceed to consolidative autologous stem cell transplant. Will continue on treatment as long as they are responding to therapy and not experiencing unacceptable side effects.

Official Title
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A Multi-center Phase II Study of CC486-CHOP in Patients With Previously Untreated Peripheral T-cell Lymphoma

Conditions
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Previously Untreated Peripheral T-cell Lymphoma

Intervention / Treatment
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* Drug: CC-486 Administration
* Drug: CHOP Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Histologically confirmed diagnosis of PTCL of the following subtypes: Nodal T-cell lymphoma with T-follicular helper (TFH) phenotype (tumor cells must express 2 or 3 TFH-related antigens, including PD1, CD10, BCL6, CXCL13, ICOS, SAP and CCR5)* Angioimmunoblastic T-cell lymphoma Follicular T-cell lymphoma PTCL/NOS, T-follicular helper (TFH) variant PTCL-NOS Anaplastic large cell lymphoma, ALK negative Anaplastic large cell lymphoma, ALK positive with IPI > 2 Adult T-cell leukemia / lymphoma No prior systemic therapy for lymphoma Measurable disease defined by a tumor mass ≥ 1.5 cm in one dimension and measurable in two dimensions ECOG performance status ≤ 2 Exclusion Criteria: Known central nervous system (CNS) involvement by lymphoma Active viral infection with HIV or hepatitis type B or C (seropositive HBV patients are eligible if they are negative for HBV DNA by PCR and receive concomitant antiviral therapy). Prior history of malignancies other than PTCL unless the patient has been disease free for ≥ 5 years from the signing of the ICF.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This is a phase II, multi-center study to determine the efficacy and safety of first-line CC-486 plus CHOP in patients with PTCL who have received no prior systemic therapy. The study has a sample size of 20, and follows two-stage minimax design for primary efficacy analysis.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CC486 +CHOP<br>CC486 +CHOP | Drug: CC-486 Administration<br>* CC-486 at 300 mg once daily is to be administered Cycle 1, Day -6 to 0 and Cycles 1 to 5, Day 8 to 21. Antiemetic prophylaxis is recommended before dosing. All efforts should be made to administer CC-486 on all scheduled days of the Cycle 1 priming dosing (7 days, Cycle 1 Day -6 to Cycle 1 Day 0) and the Cycle 1-5 dosing (14 days, Day 8-21). A dose missed earlier in a day can be administered later that day as long as it is taken at least 8 hours before the next scheduled dose. Any missed dose should not be taken beyond the last scheduled day of CC-486 administration for the cycle, but should be returned by the subject for CC 486 accountability. If vomiting occurs after a dose of CC-486 is administrated, that dose should not be made up later that day.<br>* Other names: Oral Azacitidine;Drug: CHOP Administration<br>* CHOP is to be administered on Days 1 to 5 of Cycles 1-6. Chemotherapy can be administer within +72h or -24h of Day 1 of each scheduled Cycle. Preparation and infusion rate are according to the package insert and local practice. The doses to be used are: Cyclophosphamide: 750 mg/m2 IV on day 1 Doxorubicin: 50 mg/m2 IV on day 1 Vincristine: 1.4 mg/m2 IV (not to exceed 2.0 mg total) on day 1 Prednisone: 100 mg PO days 1-5<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response Rate | Complete response rate (CR) of CC486-CHOP in PTCL by Lugano Criteria for target lesions, and the Deauville Criteria (5 point scale) assessed by PET or CT; CR (complete metabolic or radiologic response) defined as Deauville score of 1, 2 or 3 by PET or regression of all target lesions to < 1.5cm in longest diameter by CT. | After Cycle 6 at 18 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kaplan-Meier Overall Survival | Overall Survival (OS) assessed by Kaplan-Meier survival analysis. The Kaplan-Meier overall survival estimate at 2 years (with 95% confidence interval) is reported. OS defined as the time from first treatment day until death (or until last follow-up if alive). | 2 years | 
| Kaplan-Meier Progression-Free Survival | Progression-free survival (PFS) assessed by Kaplan-Meier survival analysis. The Kaplan-Meier progression-free survival estimate at 2 years (with 95% confidence interval) is reported. PFS defined as the time from first treatment day until objective or symptomatic progression or death (or date of last follow-up if no progression/death). | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Peripheral T-cell Lymphoma, Azacitidine, Lymphoma