This phase I/II trial studies the best dose and side effects of dendritic cell therapy, cryosurgery and pembrolizumab in treating patients with non-Hodgkin lymphoma. Vaccines, such as dendritic cell therapy made from a person's tumor cells and white blood cells may help the body build an effective immune response to kill tumor cells. Cryosurgery kills cancer cells by freezing them. 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 dendritic cell therapy, cryosurgery and pembrolizumab may work better at treating non-Hodgkin lymphoma.
PRIMARY OBJECTIVES: I. Evaluate the optimal dose schedule, safety and tolerability as measured by the incidence of significant toxicity of combination therapy with anti-PD-1 monoclonal antibody, cryoablation, and intra-tumor injection of autologous dendritic cell into the cryoablated tumor. (Phase I) II. Test the efficacy (overall response rate) of combination therapy with anti-PD-1 monoclonal antibody, cryoablation, and intra-tumor injection of autologous dendritic cell vaccine. (Phase II) SECONDARY OBJECTIVES: I. Evaluate the feasibility of this combination immunotherapy. (Phase I) II. Evaluate patient quality of life. (Phase I) III. Evaluate the partial response (PR) and complete response (CR) rate of this combination immunotherapy. (Phase II) IV. Evaluate the progression free survival, treatment free survival, duration of response, disease-free rate at 2 years, and overall survival of this combination immunotherapy. (Phase II) V. Evaluate the safety of this combination immunotherapy. (Phase II) CORRELATIVE OBJECTIVES: I. Assess the effect of combination immunotherapy on patients' immune status and anti-tumor immune response. (Phase II) II. Assess the potential association between PD-1/PD-L1/PD-L2 expression in tumor and blood with clinical efficacy. (Phase II) III. Assess the potential association between tumor antigen mutations and antigen-specific immune response with clinical efficacy. (Phase II) IV. Evaluate patient quality of life. (Phase II) OUTLINE: This is a phase I, dose-escalation study followed by a phase II study. Patients receive pembrolizumab intravenously (IV) on day 1. Treatment repeats every 21 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive dendritic cell therapy intratumorally (IT) on days 2, 8, and 15 of cycles 2 and 3, and day 2 of cycles 4 and 5. Patients undergo cryosurgery on day 2 of cycle 2 and receive pneumococcal 13-valent conjugate vaccine by injection on day 2 of cycles 2-5. Treatment repeats every 21 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity. Patients who are CR, PR, or stable disease (SD) after completion of therapy, may receive pembrolizumab for an additional 18 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months during the first year post-treatment, every 4 months during the second year post-treatment, and then every 6 months for up to 2 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
11
Undergo cryosurgery
Given IT
Correlative studies
Given IV
Given by injection
Ancillary studies
Mayo Clinic in Rochester
Rochester, Minnesota, United States
Number of Patients That Experienced a Dose Limiting Toxicity (DLT)
Maximum tolerated dose (MTD) will be defined as the dose level that does not induce dose limiting toxicity in at least one-third of patients. DLTs are defined as Grade 4 or 5 ANC or PLT for at least 7 days, grade 3 plus Infections and infestations, febrile neutropenia defined as fever ≥38.5oC (38 \>1 hour) with grade 4 plus neutropenia, at least Grade 3 erythema multiforme, ulceration, or urticaria that does not resolve to Grade 2 or less within \> three weeks, at least grade 3 bronchial obstruction, pneumonitis, or wheezing at least grade 3 allergic reaction or autoimmunity at least grade 3 that does not resolve to less than Grade 2\> less than or equal to 72 hours per NCI Common Terminology Criteria for Adverse Events.
Time frame: 56 days
Percentage of Complete Responses of Combination Therapy With Pembrolizumab, Cryoablation, and Intra-tumor Injection of Autologous Dendritic Cells (DC) at Maximum Tolerated Dose (MTD) Dose
The percentage of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated.
Time frame: 24 months
Progression Free Survival
The distribution of survival time will be estimated using the method of Kaplan-Meier.
Time frame: 24 months
Treatment Free Survival
The distribution of treatment-free survival will be estimated using the method of Kaplan-Meier.
Time frame: 34 months
Duration of Response
The distribution of duration of complete response will be estimated using the method of Kaplan-Meier.
Time frame: 11 months
Disease Free Survival Rate
The percentage of patients without disease at two years post start of treatment.
Time frame: 2 years
Overall Survival
The distribution of survival time will be estimated using the method of Kaplan-Meier.
Time frame: 5 years
Percentage of Patients With Grade 4 or 5 Adverse Events
Will be assessed by Common Terminology Criteria for Adverse Events version 4.0.
Time frame: Up to 4 years
Percent of Patients With Improved Quality of Life
Will be measured using the Functional Assessment of Cancer Therapy-lymphoma. The assessment will be scored according to the scoring algorithm. Changes from baseline will be calculated at each assessment time points. Mean change scores at each time point will be calculated to determine if quality of life is reduced over the course of treatment. Longitudinal techniques will be employed to describe changes over time.
Time frame: 4 years
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