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

• ClinicalTrials.gov Identifier: NCT03542266
• Recruitment Status: Completed
• First Posted: May 31, 2018
• Results First Posted: May 20, 2021
• Last Update Posted: August 22, 2023
• Sponsor: Weill Medical College of Cornell University
• Collaborator: Celgene Corporation
• Information provided by (Responsible Party): Weill Medical College of Cornell University

Tracking Information

• First Submitted Date: May 18, 2018
• First Posted Date: May 31, 2018
• Results First Submitted Date: March 10, 2021
• Results First Posted Date: May 20, 2021
• Last Update Posted Date: August 22, 2023
• Actual Study Start Date: June 1, 2018
• Actual Primary Completion Date: March 25, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 26, 2021)

Complete Response Rate [ Time Frame: After Cycle 6 at 18 weeks ]

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.

Original Primary Outcome Measures (submitted: May 18, 2018)

Complete Response Rate [ Time Frame: After Cycle 6 at 18 weeks ]

Complete response rate (CR) of CC486-CHOP in PTCL by 2014 International Working Group (IWG) criteria, and the Deauville Criteria for scan interpretation.

Current Secondary Outcome Measures (submitted: July 28, 2023)

• Kaplan-Meier Overall Survival [ Time Frame: 2 years ]
  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).
• Kaplan-Meier Progression-Free Survival [ Time Frame: 2 years ]
  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).

Original Secondary Outcome Measures (submitted: May 18, 2018)

• Overall Survival [ Time Frame: 2 years ]
  Overall Survival (OS) assessed by Kaplan-Meier survival analysis and 95% confidence intervals will be calculated using Greenwood's formula. OS will be defined as the time from first treatment day until death.
• Progression-Free Survival [ Time Frame: 2 years ]
  Progression-free survival (PFS), assessed by Kaplan-Meier survival analysis and 95% confidence intervals will be calculated using Greenwood's formula. PFS will be defined as the time from first treatment day until objective or symptomatic progression or death.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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.

• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention 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)
Primary Purpose: Treatment

• Condition: Previously Untreated Peripheral T-cell Lymphoma

Intervention

• Drug: CC-486 Administration
  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.
  Other Name: Oral Azacitidine
• Drug: CHOP Administration

  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

Study Arms

Experimental: CC486 +CHOP

CC486 +CHOP

Interventions:

• Drug: CC-486 Administration
• Drug: CHOP Administration

• Publications *: Yoon SE, Cho J, Kim YJ, Kim SJ, Kim WS. Real-World Efficacy of 5-Azacytidine as Salvage Chemotherapy for Angioimmunoblastic T-cell Lymphoma. Clin Lymphoma Myeloma Leuk. 2022 Nov;22(11):e972-e980. doi: 10.1016/j.clml.2022.07.009. Epub 2022 Jul 17.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 10, 2021): 21
• Original Estimated Enrollment (submitted: May 18, 2018): 20
• Actual Study Completion Date: July 25, 2022
• Actual Primary Completion Date: March 25, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03542266
• Other Study ID Numbers: 1711018777
• 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

• Plan to Share IPD: No

• Current Responsible Party: Weill Medical College of Cornell University
• Original Responsible Party: Same as current
• Current Study Sponsor: Weill Medical College of Cornell University
• Original Study Sponsor: Same as current
• Collaborators: Celgene Corporation

Investigators

• Principal Investigator: Jia Ruan, MD, Ph.D; Weill Medical College of Cornell University

• PRS Account: Weill Medical College of Cornell University
• Verification Date: July 2023