RADVAX™ for Relapsed/Refractory Non-Hodgkin Lymphoma: A Phase II Trial of Pembrolizumab + Low Dose Radiotherapy

NCT04827862 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: UPCC 56419844686
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This study is an open-label Phase II trial of non-Hodgkin lymphoma patients receiving initial treatment with the immunomodulatory agent, pembrolizumab, plus low-dose (4 Gy x 5) involved-site radiotherapy. Eligible patients will have r/r disease with at least 2 sites of measurable disease (≥1.0 cm), and must be eligible for treatment with pembrolizumab. Biosamples (blood and, where available, tumor) will be collected as outlined below. Pembrolizumab will be continued after RT until disease progression, drug intolerance, or at the discretion of the treating medical oncologist.

Conditions

Non Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• CR rate

  12 weeks

Secondary Outcomes (5)

• Time to best response

  20 weeks

• Duration of best response

  5 years

• Progression-free survival (PFS)

  5 years

• Overall survival

  5 years

• Duration of immunotherapy use for the pembrolizumab + RT induction CR cohort

  5 years

Study Arms (1)

Pembrolizumab and Radiation Therapy

EXPERIMENTAL

pembrolizumab plus low-dose (4 Gy x 5) involved-site radiotherapy

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

pembrolizumab plus low-dose (4 Gy x 5) involved-site radiotherapy

Pembrolizumab and Radiation Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of relapsed/refractory non-Hodgkin lymphoma (defined below) will be enrolled in this study.
• Male participants:
• \- A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period.
• Female participants:
• \- A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
• A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 120 days after the last dose of study treatment.
• \- The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• \- Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the start date of radiation.
• Have adequate organ function as defined in the following table (Table 1). Specimens must be collected within 10 days prior to the start of study drug Pembrolizumab.
• Note: The patient can be considered eligible and started on RT prior to confirming adequate organ function is met provided they meet the rest of the eligibility criteria. Adequate organ function needs to be confirmed prior to starting the Pembrolizumab. If it is found that the patient does not have adequate organ function post starting RT and prior to administering Pembrolizumab they will be withdrawn from the study and considered as a screen failure.
• \- Pathologically confirmed B-cell, T-cell, aggressive, or indolent non-Hodgkin lymphoma for whom pembrolizumab is clinically indicated per physician discretion as documented in a separate Medical Oncology note.
• \- Relapsed/refractory disease treated with at least 2 lines of prior therapy.

You may not qualify if:

• A WOCBP who has a positive urine pregnancy test within 72 hours prior to the first fraction of radiation (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.
• A patient may be considered eligible pending negative pregnancy test within 72 hours prior to the first fraction of radiation.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137).
• Has received prior systemic anti-cancer therapy including investigational agents within 2 weeks prior to the first fraction of radiation.
• Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.
• Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
• \- Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
• \- Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
• \- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
• Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• \- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• \- Has a known additional malignancy that is progressing or has required active treatment within the past 1 year. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, breast cancer, prostate cancer, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
• \- Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• \- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead

Study Sites (1)

Abamson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Michael LaRiviere, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2021
• First Posted: April 1, 2021
• Study Start: July 1, 2022
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: December 5, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)