Dendritic Cell Therapy, Cryosurgery, and Pembrolizumab in Treating Patients With Non-Hodgkin Lymphoma

NCT03035331 | Completed Phase 1 Results DMC FDA Drug

• 4 other identifiers: MC1685P50CA09727416-005856R01CA219960
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Aggressive Non-Hodgkin Lymphoma; Indolent Non-Hodgkin Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent T-Cell Non-Hodgkin Lymphoma; Small Lymphocytic Lymphoma; Recurrent Primary Mediastinal (Thymic) Large B-Cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  24 months

Secondary Outcomes (7)

• Progression Free Survival

  24 months

• Treatment Free Survival

  34 months

• Duration of Response

  11 months

• Disease Free Survival Rate

  2 years

• Overall Survival

  5 years

Other Outcomes (2)

• Radiologic Analysis

  Up to 4 years

• Change in Immunologic Correlates

  Baseline up to 4 years

Study Arms (1)

Treatment (pembrolizumab, dendritic cell therapy, cryosurgery)

EXPERIMENTAL

Patients receive pembrolizumab 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 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 SD after completion of therapy, may receive pembrolizumab for an additional 18 cycles in the absence of disease progression or unacceptable toxicity.

Procedure: Cryosurgery; Biological: Dendritic Cell Therapy; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Biological: Pneumococcal 13-valent Conjugate Vaccine; Other: Quality-of-Life Assessment

Interventions

Cryosurgery PROCEDURE

Undergo cryosurgery

Also known as: Ablation, Cryo, Cryoablation, cryosurgical ablation

Treatment (pembrolizumab, dendritic cell therapy, cryosurgery)

Dendritic Cell Therapy BIOLOGICAL

Given IT

Also known as: Dendritic Cell Vaccine Therapy

Treatment (pembrolizumab, dendritic cell therapy, cryosurgery)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (pembrolizumab, dendritic cell therapy, cryosurgery)

Pembrolizumab BIOLOGICAL

Given IV

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

Treatment (pembrolizumab, dendritic cell therapy, cryosurgery)

Pneumococcal 13-valent Conjugate Vaccine BIOLOGICAL

Given by injection

Also known as: PCV 13, PCV13 Vaccine, Prevnar 13

Treatment (pembrolizumab, dendritic cell therapy, cryosurgery)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (pembrolizumab, dendritic cell therapy, cryosurgery)

Eligibility Criteria

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

You may qualify if:

• Age \>= 18 years
• Histological confirmation of biopsy-proven non-Hodgkin lymphoma, excluding chronic lymphocytic leukemia, primary central nervous system (CNS) lymphoma and Burkitt's lymphoma; Note: small lymphocytic lymphoma (SLL) is allowed
• Patients with indolent non-Hodgkin lymphoma (NHL) must have had \>= 1 regimen of rituximab-containing regimen; Note: this includes follicular lymphoma (FL), marginal lymphoma and mucosa-associated lymphoid tissue (MALT)
• Patients with aggressive NHL must have had \>= 2 regimens; Note: This includes diffuse large B cell lymphoma (DLBCL), mantle cell lymphoma (MCL), primary mediastinal large B-cell lymphoma (PMBCL), and T cell lymphoma
• Patient with aggressive NHL must have received prior therapy - at a minimum:
• Anti-CD20 monoclonal antibody unless tumor is CD20 negative and
• An anthracycline containing regimen
• Transformed FL must have had therapy for FL and be refractory to chemotherapy for DLBCL
• Chemotherapy refractory disease in aggressive NHL is defined as
• Stable disease of =\< 12 months or progressive disease as best response to most recent chemotherapy containing regimen
• Disease progression or recurrence =\< 12 months of prior autologous stem cell transplantation (SCT)
• Patients with aggressive NHL must have failed autologous hematopoietic stem cell transplantation (HSCT), or are ineligible or not consenting to autologous HSCT
• Patient must have at least 3 measurable lesions that are \>= 1.5 cm in one dimension; one of the lesions must be \>= 2.0 cm and is amenable to image-guided cryoablation and multiple vaccine injections as determined by interventional radiology and principal investigator (PI) (including tumors that can be safely accessed using imaging guidance and treated with minimal risk to adjacent structures)
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
• Absolute neutrophil count (ANC) \>= 1000/mm\^3 (obtained =\< 14 days prior to registration)

You may not qualify if:

• Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
• Pregnant women
• Nursing women
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
• Serious non-malignant disease such as active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations or other conditions which in the opinion of the investigator would compromise protocol objectives
• Currently receiving or have received any other investigational agent considered as a treatment for the primary neoplasm =\< 28 days or within 4 half-lives (whichever is shorter) of the agent prior to registration
• History of other primary malignancy requiring systemic treatment within 6 months of protocol enrollment; patients must not be receiving chemotherapy or immunotherapy for another cancer; patients must not have another active malignancy requiring active treatment with the following acceptable EXCEPTIONS:
• Basal cell carcinoma, squamous cell carcinoma, or melanoma of the skin that has undergone or will undergo potentially curative therapy
• In situ cervical cancer that has undergone or will undergo potentially curative therapy
• Prior allogeneic bone marrow or peripheral blood stem cell transplantation
• Prior autologous bone marrow or peripheral blood stem cell transplantation =\< 100 days prior to registration or if recovery from the transplant is inadequate
• Major surgery other than diagnostic surgery =\< 4 weeks prior to registration
• Prior chemotherapy or radiation therapy =\< 2 weeks prior to registration or who has not recovered (i.e. to =\< grade 1 or baseline) from an adverse event due to the previously administered therapy
• History of hypersensitivity and anaphylactoid reactions to pneumococcal vaccine or any component of the formulation, including diphtheria toxoid
• Active autoimmune disease such as Crohn's disease, rheumatoid arthritis, Sjogren's disease, systemic lupus erythematosus, or similar conditions requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease/syndrome difficult to control in the past

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Cryosurgery; pembrolizumab; 13-valent pneumococcal vaccine

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ablation Techniques; Surgical Procedures, Operative

Results Point of Contact

• Title: Yi Lin
• Organization: Mayo Clinic

Lin.Yi@mayo.edu

507-293-5189

Study Officials

• Yi Lin, MD, PhD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2017
• First Posted: January 30, 2017
• Study Start: August 15, 2017
• Primary Completion: January 25, 2022
• Study Completion: September 10, 2022
• Last Updated: May 4, 2026
• Results First Posted: May 16, 2025

Record last verified: 2024-12

Locations

US (1)