Phase II Study of Pembrolizumab and Fractionated External Beam Radiotherapy in Patients With Relapsed and Refractory Non-Hodgkin Lymphoma
Overview
- Phase
- Phase 2
- Intervention
- External Beam Radiation Therapy
- Conditions
- Primary Mediastinal (Thymic) Large B-Cell Lymphoma
- Sponsor
- M.D. Anderson Cancer Center
- Enrollment
- 17
- Locations
- 1
- Primary Endpoint
- Overall Response Rate of Pembrolizumab With Concurrent Fractionated External Beam Radiotherapy (EBRT) Among Patients With Relapsed and Refractory Non-Hodgkin Lymphoma (NHL)
- Status
- Completed
- Last Updated
- 3 months ago
Overview
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.
Detailed Description
PRIMARY OBJECTIVES: I. To determine the overall response rate (ORR) of pembrolizumab with concurrent fractionated external beam radiotherapy (EBRT) among patients with relapsed and refractory non-Hodgkin lymphoma (NHL). SECONDARY OBJECTIVES: I. To determine the safety of pembrolizumab with fractionated EBRT in patients with relapsed and refractory NHL. II. To determine the overall response rate and complete response rate (CRR) of irradiated and non-irradiated lesions to treatment with concurrent pembrolizumab and fractionated EBRT in patients with relapsed and refractory NHL. III. To determine the progression free survival (PFS) of pembrolizumab in combination with fractionated EBRT. IV. To determine the overall survival (OS) of pembrolizumab in combination with fractionated EBRT. V. To determine the duration of response of irradiated and non-irradiated lesions after concurrent pembrolizumab and fractionated EBRT. EXPLORATORY OBJECTIVES: I. To identify tumor and peripheral blood markers predictive of response to concurrent pembrolizumab and low to moderate dose EBRT in the setting of relapsed and refractory NHL. II. To determine if a course of hypo-fractionated EBRT can improve response after progressive disease among patients treated with fractionated EBRT and pembrolizumab. OUTLINE: 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 intravenously (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. After completion of study treatment, patients are followed up at 30 days, every 3 months for 1 year and then every 6 months thereafter.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
- •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
- •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)
Exclusion Criteria
- •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
Arms & Interventions
Treatment (EBRT, pembrolizumab)
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.
Intervention: External Beam Radiation Therapy
Treatment (EBRT, pembrolizumab)
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.
Intervention: Pembrolizumab
Outcomes
Primary Outcomes
Overall Response Rate of Pembrolizumab With Concurrent Fractionated External Beam Radiotherapy (EBRT) Among Patients With Relapsed and Refractory Non-Hodgkin Lymphoma (NHL)
Time Frame: Every 3 months until withdrawal of consent, becoming lost to follow-up, or death (an average of 14 months).
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.
Secondary Outcomes
- 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).)
- Progression Free Survival(1.8 ~ 6.5 months)
- Overall Survival(Every 3 months until withdrawal of consent, becoming lost to follow-up, or death.)
- Safety of Pembrolizumab With Fractionated EBRT(Through Study Completion (an average of 14 months))