Pembrolizumab and External Beam Radiation Therapy in Treating Patients With Relapsed or Refractory Non-Hodgkin Lymphoma

NCT03210662 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2017-0341NCI-2018-01123
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well pembrolizumab and external beam radiation therapy work in treating patients with non-Hodgkin lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving pembrolizumab and external beam radiation therapy may work better in treating patients with non-Hodgkin lymphoma than pembrolizumab alone.

Conditions

Refractory Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma; Primary Mediastinal (Thymic) Large B-Cell Lymphoma; Recurrent Aggressive Non-Hodgkin Lymphoma; Recurrent Mature T- Cell and NK-Cell Non-Hodgkin Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent T-Cell Non-Hodgkin Lymphoma; Recurrent Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma; Refractory Aggressive Non-Hodgkin Lymphoma; Refractory Non-Hodgkin Lymphoma; Refractory T-Cell Non-Hodgkin Lymphoma; Transformed Marginal Zone Lymphoma to Diffuse Large B-Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate of Pembrolizumab With Concurrent Fractionated External Beam Radiotherapy (EBRT) Among Patients With Relapsed and Refractory Non-Hodgkin Lymphoma (NHL)

  Disease response will be assessed via revised Lugano classification for the response assessment of Hodgkin and non-Hodgkin lymphoma. The end of treatment assessment is determined by positron emission tomography (PET)-computed tomography (CT) imaging for patients with fluoro-deoxyglucose (FDG) avid hematologic malignancies. For patients with FDG-avid disease, the Deauville Criteria will be utilized for PET-CT scoring on a 5 point 5-point scale, in accordance with standard response criteria. A score of 1-3 is considered negative a score of 4-5 is considered positive for the presence of active lymphoma.

  Every 3 months until withdrawal of consent, becoming lost to follow-up, or death (an average of 14 months).

Secondary Outcomes (4)

• Progression Free Survival

  1.8 ~ 6.5 months

• Overall Survival

  Every 3 months until withdrawal of consent, becoming lost to follow-up, or death.

• Overall and Complete Response Rate of Irradiated vs Non-Irradiated Lesions

  Every 3 months until withdrawal of consent, becoming lost to follow-up, or death (an average of 14 months).

• Safety of Pembrolizumab With Fractionated EBRT

  Through Study Completion (an average of 14 months)

Study Arms (1)

Treatment (EBRT, pembrolizumab)

EXPERIMENTAL

Beginning on day 1, patients undergo fractionated EBRT daily for 5 consecutive days a week for up to 12 or 22 treatments. Patients also receive pembrolizumab IV over 1 hour on day 2. Treatment with pembrolizumab repeats every 21 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity.

Radiation: External Beam Radiation Therapy; Biological: Pembrolizumab

Interventions

External Beam Radiation Therapy RADIATION

Undergo EBRT

Also known as: Definitive Radiation Therapy, EBRT, External Beam Radiotherapy, External Beam RT, external radiation, External Radiation Therapy, external-beam radiation

Treatment (EBRT, pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (EBRT, pembrolizumab)

Eligibility Criteria

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

You may qualify if:

• Have at least one site of lymphomatous disease amenable to external beam radiation therapy (EBRT)
• Have pathologic confirmation of aggressive non-Hodgkin lymphoma (including diffuse large B cell lymphoma, transformed follicular lymphoma, transformed marginal zone lymphoma, primary mediastinal B-cell lymphoma, T cell lymphoma and NK T-cell lymphoma). Patients with indolent B cell lymphoma are excluded
• Be willing and able to provide written informed consent/assent for the trial
• Have measurable disease (\>= 1.5 cm in the longest diameter for nodal or extranodal disease)
• 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. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen. Note: If submitting unstained cut slides, newly cut slides should be submitted to the testing laboratory within 14 days from the date slides are cut
• 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 date of allocation/randomization
• Absolute neutrophil count (ANC) \>= 1,000 /mcL (performed within 10 days of treatment initiation)
• Platelets \>= 50,000 / mcL (performed within 10 days of treatment initiation)
• Hemoglobin \>= 8 g/dL or \>= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment) (performed within 10 days of treatment initiation)
• Serum creatinine OR measured or calculated creatinine clearance (creatinine clearance should be calculated per institutional standard) (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) =\< 1.5 x upper limit of normal (ULN) OR \>= 60 mL/min for subject with creatinine levels \> 1.5 x institutional ULN (performed within 10 days of treatment initiation)
• Serum total bilirubin =\< 1.5 x ULN OR direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 ULN (performed within 10 days of treatment initiation)
• Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) =\< 2.5 x ULN OR =\< 5 x ULN for subjects with liver metastases (performed within 10 days of treatment initiation)
• Albumin \>= 2.5 mg/dL (performed within 10 days of treatment initiation)
• International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (performed within 10 days of treatment initiation)
• Activated partial thromboplastin time (aPTT) =\< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (performed within 10 days of treatment initiation)

You may not qualify if:

• Has had prior radiation therapy to the potential radiation target such that additional radiation therapy is considered unsafe by the treating radiation oncologist
• Has a history of allogeneic stem cell transplantation
• Has a diagnosis of active scleroderma or lupus or any other autoimmune disease that by the opinion of the treating radiation oncologist would put the patient at unacceptable risk of toxicity
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
• Has a known history of active Bacillus tuberculosis (TB)
• Hypersensitivity to pembrolizumab or any of its excipients
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to a previously administered agent
• Note: subjects with =\< grade 2 neuropathy are an exception to this criterion and may qualify for the study
• Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
• Has a known additional malignancy that is progressing or requires active treatment within the past 3 years. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
• Has known active central nervous system (CNS) lymphoma or lymphomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment
• 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
• Has history of (non-infectious) pneumonitis that required steroids, evidence of interstitial lung disease or active, non-infectious pneumonitis

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Lymphoma, T-Cell; 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

Results Point of Contact

• Title: Chelsea C. Pinnix, MD
• Organization: M.D. Anderson Cancer Center

ccpinnix@mdanderson.org

713-563-2300

Study Officials

• Chelsea C Pinnix

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: July 5, 2017
• First Posted: July 7, 2017
• Study Start: February 1, 2018
• Primary Completion: October 28, 2025
• Study Completion: October 31, 2025
• Last Updated: January 13, 2026
• Results First Posted: January 13, 2026

Record last verified: 2026-01

Locations

US (1)