Pembrolizumab and Radiotherapy for Previously Untreated Patients With Limited Stage NK/T Cell Lymphoma Who Are Not Eligible to Chemotherapy
Overview
- Phase
- Phase 2
- Intervention
- Pembrolizumab
- Conditions
- Lymphoma, Extranodal NK-T-Cell
- Sponsor
- International Extranodal Lymphoma Study Group (IELSG)
- Enrollment
- 30
- Locations
- 2
- Primary Endpoint
- Progression Free Survival (PFS) rate at 2 years - The proportion of patients without disease progression after 2 years from treatment start
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
Aim of the trial is to evaluate the activity and tolerability of the anti PD1 agent Pembrolizumab in combination with RadioTherapy for the initial treatment of previously untreated patients with limited stage NK/T cell lymphoma who are not eligible to chemotherapy.
It is planned to enroll 30 patients in chinese sites.
All eligible patients will be treated with standard radiotherapy and concurrent pembrolizumab administered intravenously every 3 weeks. After 6 cycles of pembrolizumab patients with complete remission, partial response and stable disease will continue with pembrolizumab maintenance up to 2 years.
Patients will be followed up to 4 years from treatment start.
Detailed Description
This is an interventional, phase II, open label, single arm, multicentric clinical trial to be conducted in China. The primary objective is to test the efficacy of concurrent RT-Pembrolizumab in patients with limited stage NK/T cell lymphoma and who are not eligible to receive chemotherapy. The secondary objectives are to further explore the efficacy and safety of a the combination of RT and Pembrolizumab as initial treatment of the patients population. All eligible patients will be treated with standard IFRT and concurrent pembrolizumab administered intravenously, over 30 minutes starting on day 1 of RT (C1D1, at the dose of 200 mg, every 3 weeks). After 6 cycles of pembrolizumab patients will undergo restaging imaging. Patients with complete remission (CR), partial response (PR) and stable disease (SD) will continue with pembrolizumab maintenance up to 2 years that will be administered intravenously, at the dose of 200 mg, over 30 minutes on day 1 every 3 weeks up to 34 cycles. The follow-up period will last up to 4 years from treatment start.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Confirmed histological diagnosis of NK/T Cell Lymphoma
- •No previous anti-lymphoma treatment
- •Age ≥ 18 years
- •Ann Arbor stage I-II
- •At least one measurable/evaluable site after diagnostic biopsy before treatment start
- •At least one of the following high-risk features: age \> 60 years, elevated LDH, stage II, primary tumor invasion
- •Patient ineligible to receive full dose standard chemotherapy
- •ECOG performance status of 0-1
- •Signed Informed consent
- •Ability to comply with the protocol
Exclusion Criteria
- •Advanced stage disease (AA stage III-IV)
- •Extranasal type NKTCL
- •History of autoimmune disease
- •History of other(s) infiltrating cancer(s) in the previous 3 years that were not treated with curative intent or who are still receiving anticancer therapy (including hormone therapy for breast or prostate cancer).
- •History of (non-infectious) pneumonitis that required steroids; evidence of interstitial lung disease or active, non-infectious pneumonitis
- •Active infection requiring systemic therapy
- •Significant cardiovascular disease, myocardial infarction in the previous 3 months, unstable arrhythmias, or unstable angina.
- •Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
- •HBsAg, HCV or HIV positivity. Positive serology is admitted for HBV and HCV but DNA/RNA test must be negative
- •Administration of a live attenuated vaccine within 4 weeks before cyle 1 day
Arms & Interventions
Pembrolizumab and Radiotherapy
Induction Phase: Standard Involved Field Radiation Therapy (IFRT) and pembrolizumab. Pembrolizumab 200 mg IV will be given over 30 minutes on day 1 of each 21 day cycle for a total of 6 cycles. IFRT will start at first cycle of Pembrolizumab and will be delivered concurrently. Patients with complete remission (CR), partial response (PR) and stable disease (SD) after Induction Phase will continue with pembrolizumab maintenance. Maintenance Phase: Pembrolizumab 200 mg IV will be given over 30 minutes on day 1 of each 21 day cycle up to 34 cycles or until disease progression or unaccepted toxicity
Intervention: Pembrolizumab
Pembrolizumab and Radiotherapy
Induction Phase: Standard Involved Field Radiation Therapy (IFRT) and pembrolizumab. Pembrolizumab 200 mg IV will be given over 30 minutes on day 1 of each 21 day cycle for a total of 6 cycles. IFRT will start at first cycle of Pembrolizumab and will be delivered concurrently. Patients with complete remission (CR), partial response (PR) and stable disease (SD) after Induction Phase will continue with pembrolizumab maintenance. Maintenance Phase: Pembrolizumab 200 mg IV will be given over 30 minutes on day 1 of each 21 day cycle up to 34 cycles or until disease progression or unaccepted toxicity
Intervention: Involved Field Radiation Therapy
Outcomes
Primary Outcomes
Progression Free Survival (PFS) rate at 2 years - The proportion of patients without disease progression after 2 years from treatment start
Time Frame: 2 years from treatment start
Response will be assessed using international criteria for response assessment in lymphomas (Cheson 2014) and their update for patients receiving checkpoint inhibitors (Cheson 2016 Lyric)
Secondary Outcomes
- 2-year Event-free survival - Proportion of patient without disease related events after 2 years from treatment start(2 years from treatment start)
- Treatment related mortality - Number of treatment related deaths(From informed consent signature to 90 days after the last study treatment administration)
- Overall Response Rate (ORR) - calculated as the sum of the complete and partial remission rates(After 4 months from treatment start (End of Induction phase) Maintenance Phase: every 4 months during the first year and then every 6 months until end of treatment. Follow up: every 4 months during first year, then every 6 months during second year)
- 2-year Overall survival - Proportion of patients alive after 2 years from treatment start(2 years from treatment start)
- Rate of adverse events - Analysis of incidence, severity and relationship of adverse events(From Informed Consent signature to 30 days for AEs or 90 for SAEs after end of treatment)
- Complete remission rate (CRR) - Proportion of patients with complete responses(After 4 months from treatment start (End of Induction phase), Maintenance Phase:every 4 months during the first year and then every 6 months until end of treatment. Follow up: every 4 months during first year, then every 6 months during second year)