Pembrolizumab and Radiotherapy for Patients With NK/T Cell Lymphoma

NCT ID: NCT04417166

Last Updated: 2025-01-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-11
• Study Completion Date: 2026-12-31

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.

Conditions

Lymphoma, Extranodal NK-T-Cell

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Pembrolizumab

Intervention Type: DRUG

50 mg powder for concentrate for solution for infusion

Involved Field Radiation Therapy

Intervention Type: RADIATION

50-54 Gy Involved Field Radiation Therapy (IFRT) as proposed by the International Lymphoma Radiation Oncology Group (ILROG) guidelines. 50 Gy is recommended in patients without primary tumor invasiveness (invasion to adjacent tissue and/or organs), 54 Gy in locally advanced cases (invasion to adjacent tissue and/or organs) or with other risk factors (age > 60 years, stage II, elevated serum LDH levels).

Intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) are recommended but not mandatory; 3-dimensional conformal RT (3D-CRT) is allowed.

Interventions

Pembrolizumab

50 mg powder for concentrate for solution for infusion

Intervention Type: DRUG

Involved Field Radiation Therapy

50-54 Gy Involved Field Radiation Therapy (IFRT) as proposed by the International Lymphoma Radiation Oncology Group (ILROG) guidelines. 50 Gy is recommended in patients without primary tumor invasiveness (invasion to adjacent tissue and/or organs), 54 Gy in locally advanced cases (invasion to adjacent tissue and/or organs) or with other risk factors (age > 60 years, stage II, elevated serum LDH levels).

Intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) are recommended but not mandatory; 3-dimensional conformal RT (3D-CRT) is allowed.

Intervention Type: RADIATION

Other Intervention Names

Keytruda

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
• Adequate hematological and organ function;
• Tumor tissue (fresh preferred, archival tissue is also acceptable)
• For women of childbearing potential a negative pregnancy test on day 1 of cycle 1 and agree to adopt an adequate measure to avoid pregnancy during study treatment and for at least one year from end of treatment
• For men agreement to remain abstinent or to use barrier contraception

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 1. Patients must not receive live, attenuate vaccines, including influenza vaccines at any time during study.
• Treatment with systemic immunosuppressive medications, including prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide and anti tumor necrosis factor (anti-TNF) agents within 2 weeks prior to cycle 1 day 1; inhaled corticosteroids are allowed.
• Evidence of suspect of CNS disease
• Clinically significant hypersensitivity (e.g., anaphylactic or anaphylactoid reactions to the compound Pembrolizumab itself or to the excipients in its formulation).
• Has had an allogenic tissue/solid organ transplant
• Known history of active TB (Bacillus Tuberculosis)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

International Extranodal Lymphoma Study Group (IELSG)

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stefano Luminari, MD

Role: STUDY_CHAIR

Ematologia, AUSL IRCCS Reggio Emilia

Weili Zhao, MD

Role: STUDY_CHAIR

Shanghai Rui Jin Hospital,Shanghai Jiao Tong University - School of Medicine

Locations

Sun Yat-sen University Cancer Center

Guangzhou, , China

Site Status: RECRUITING

Shanghai Rui-Jin Hospital

Shanghai, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Emanuele Zucca, MD

Role: CONTACT

ielsg@ior.usi.ch

+41 58 666 ext. 7321

Facility Contacts

Zhiming Li, MD

Role: primary

lizhm@sysucc.org.cn

Weili Zhao, MD, PhD

Role: primary

zhao.weili@yahoo.com

Other Identifiers

IELSG50

Identifier Type: -

Identifier Source: org_study_id