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Pembrolizumab and Radiotherapy for Patients With NK/T Cell Lymphoma

Primary Purpose

Lymphoma, Extranodal NK-T-Cell

Status

Recruiting

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Pembrolizumab

Involved Field Radiation Therapy

About this trial

This is an interventional treatment trial for Lymphoma, Extranodal NK-T-Cell

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

Shanghai Rui-Jin HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Pembrolizumab and Radiotherapy

Arm Description

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

Outcomes

Primary Outcome Measures

Progression Free Survival (PFS) rate at 2 years - The proportion of patients without disease progression after 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 Outcome Measures

Complete remission rate (CRR) - Proportion of patients with complete responses

CRR defined according to Cheson 2014 criteria

2-year Event-free survival - Proportion of patient without disease related events after 2 years from treatment start

Treatment related mortality - Number of treatment related deaths

2-year Overall survival - Proportion of patients alive after 2 years from treatment start

Rate of adverse events - Analysis of incidence, severity and relationship of adverse events

Adverse Events severity will be classified according to the National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) V. 5.0

Overall Response Rate (ORR) - calculated as the sum of the complete and partial remission rates

ORR defined according to Cheson 2014 criteria

Full Information

NCT ID

NCT04417166

First Posted

June 2, 2020

Last Updated

May 19, 2023

Sponsor

International Extranodal Lymphoma Study Group (IELSG)

1. Study Identification

Unique Protocol Identification Number

NCT04417166

Brief Title

Pembrolizumab and Radiotherapy for Patients With NK/T Cell Lymphoma

Official Title

Pembrolizumab and Radiotherapy for Previously Untreated Patients With Limited Stage NK/T Cell Lymphoma Who Are Not Eligible to Chemotherapy

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Recruiting

Study Start Date

February 11, 2022 (Actual)

Primary Completion Date

December 2024 (Anticipated)

Study Completion Date

December 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

International Extranodal Lymphoma Study Group (IELSG)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lymphoma, Extranodal NK-T-Cell

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Pembrolizumab and Radiotherapy

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Pembrolizumab

Other Intervention Name(s)

Keytruda

Intervention Description

50 mg powder for concentrate for solution for infusion

Intervention Type

Radiation

Intervention Name(s)

Involved Field Radiation Therapy

Intervention Description

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.

Primary Outcome Measure Information:

Title

Progression Free Survival (PFS) rate at 2 years - The proportion of patients without disease progression after 2 years from treatment start

Description

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)

Time Frame

2 years from treatment start

Secondary Outcome Measure Information:

Title

Complete remission rate (CRR) - Proportion of patients with complete responses

Description

CRR defined according to Cheson 2014 criteria

Time Frame

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

Title

2-year Event-free survival - Proportion of patient without disease related events after 2 years from treatment start

Time Frame

2 years from treatment start

Title

Treatment related mortality - Number of treatment related deaths

Time Frame

From informed consent signature to 90 days after the last study treatment administration

Title

2-year Overall survival - Proportion of patients alive after 2 years from treatment start

Time Frame

2 years from treatment start

Title

Rate of adverse events - Analysis of incidence, severity and relationship of adverse events

Description

Adverse Events severity will be classified according to the National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) V. 5.0

Time Frame

From Informed Consent signature to 30 days for AEs or 90 for SAEs after end of treatment

Title

Overall Response Rate (ORR) - calculated as the sum of the complete and partial remission rates

Description

ORR defined according to Cheson 2014 criteria

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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)

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Emanuele Zucca, MD

Phone

+41 58 666

Ext

7321

ielsg@ior.usi.ch

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Stefano Luminari, MD

Organizational Affiliation

Ematologia, AUSL IRCCS Reggio Emilia

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Weili Zhao, MD

Organizational Affiliation

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

Official's Role

Study Chair

Facility Information:

Facility Name

Shanghai Rui-Jin Hospital

City

Shanghai

ZIP/Postal Code

200025

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Weili Zhao, MD, PhD

zhao.weili@yahoo.com

First Name & Middle Initial & Last Name & Degree

Weili Zhao, MD, PhD

12. IPD Sharing Statement

Learn more about this trial

Pembrolizumab and Radiotherapy for Patients With NK/T Cell Lymphoma

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