Radiation Therapy, Plasma Exchange, and Immunotherapy (Pembrolizumab or Nivolumab) for the Treatment of Melanoma

Radiation Therapy, Plasma Exchange, and Immunotherapy in Melanoma

This early phase I trial investigates how well radiation therapy, plasma exchange, and pembrolizumab or nivolumab work in treating patients with melanoma. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Plasma exchange (also known as "plasmapheresis") is a way to "clean" or "flush out" the blood. Immunotherapy with monoclonal antibodies, such as pembrolizumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Plasma exchange may help to improve the effect of standard radiation therapy and immunotherapy treatment on tumor cells of patients with melanoma.

Study Overview

• Status: Completed
• Conditions: Melanoma
• Intervention / Treatment: Biological: Nivolumab; Procedure: Magnetic Resonance Imaging; Procedure: Computed Tomography; Biological: Pembrolizumab; Procedure: Biospecimen Collection; Radiation: Radiation Therapy; Procedure: Positron Emission Tomography; Biological: Therapeutic Exchange Plasma

Detailed Description

PRIMARY OBJECTIVE:

I. To determine the kinetics of soluble (s)PD-L1 removal and regeneration by plasma exchange in patients with melanoma.

SECONDARY OBJECTIVES:

I. To observe response at 3 months after plasma exchange plus immunotherapy. II. To observe ongoing response at approximate 3 month intervals after plasma exchange plus immunotherapy.

CORRELATIVE RESEARCH OBJECTIVES:

I. To determine the effects of plasma exchange on immune cell function. II. To observe the kinetics of extracellular vesicles (EVs) after plasma exchange in patients with melanoma.

OUTLINE:

Patients undergo radiation therapy daily on days 1-5 (weekdays). Patients then undergo therapeutic plasma exchange over 1-2 hours on the first session starting on the last day of radiation therapy and the last session ending prior to immunotherapy. Beginning day 5, patients receive pembrolizumab intravenously (IV) or nivolumab IV. Treatment with pembrolizumab continues every 3 weeks or treatment with nivolumab continues every 2 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection throughout the study and standard of care (SOC) computed tomography (CT), positron emission tomography (PET), and/or magnetic resonance imaging (MRI) scans as clinically indicated during follow-up.

After completion of study treatment, patients are followed up at 3 weeks and then for up to 2 years.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histological confirmation of melanoma. Patients may have completed biopsy outside of Mayo Clinic, but there must be an internal review done to confirm diagnosis prior to confirming eligibility
• Measurable or non-measurable disease
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) =< 3
• sPD-L1 levels > 1.7 ng/ml by enzyme-linked immunosorbent assay (ELISA)
• Negative pregnancy test done =< 7 days prior to radiation therapy, for women of childbearing potential only
• Provide written informed consent
• Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)
• Willing to provide blood samples for correlative research purposes

Exclusion Criteria:

• Persons taking a biotin supplement
• sPD-L1 level < 1.7 ng/ml by ELISA
• Pregnant or nursing women
• Men or women of childbearing potential who are unwilling to employ adequate contraception

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (radiation therapy, plasma exchange, immunotherapy); Patients undergo radiation therapy daily on days 1-5 (weekdays). Patients then undergo therapeutic plasma exchange over 1-2 hours on the first session starting on the last day of radiation therapy and the last session ending prior to immunotherapy. Beginning day 5, patients receive pembrolizumab IV or nivolumab IV. Treatment with pembrolizumab continues every 3 weeks or treatment with nivolumab continues every 2 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection throughout the study and SOC CT, PET, and/or MRI scans as clinically indicated during follow-up.

Biological: Nivolumab; Given IV; Other Names: BMS-936558; MDX-1106; NIVO; ONO-4538; Opdivo; CMAB819; Nivolumab Biosimilar CMAB819; Nivolumab Biosimilar ABP 206; Nivolumab Biosimilar BCD-263; Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; NMR Imaging; NMRI; nuclear magnetic resonance imaging; Magnetic Resonance Imaging (MRI); sMRI; Magnetic resonance imaging (procedure); MRIs; Structural MRI; MRS Scan; Procedure: Computed Tomography; Undergo CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Tomography; tomography; CT SCAN; computerized axial tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Biological: Pembrolizumab; Given IV; Other Names: Keytruda; MK-3475; Lambrolizumab; SCH 900475; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Radiation: Radiation Therapy; Undergo radiation therapy; Other Names: Cancer Radiotherapy; ENERGY_TYPE; Irradiate; Irradiated; Irradiation; Radiation; Radiation Therapy, NOS; Radiotherapeutics; Radiotherapy; RT; Therapy, Radiation; Procedure: Positron Emission Tomography; Undergo PET; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; PT; positron emission tomography scan; Positron emission tomography (procedure); Biological: Therapeutic Exchange Plasma; Undergo therapeutic plasma exchange; Other Names: TEP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of treatment approach	Feasibility will be assessed by being able to complete the study accrual in a reasonable time period.	Up to 2 years
Kinetics of soluble (s)PD-L1 removal and regeneration by plasma exchange in patients with melanoma	Graphical methods and descriptive statistics will be used to explore this endpoint. Assessed by the change in the sPD-L1 levels over time across the different timepoints of interest.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate	Overall response rate is the proportion of patients with a tumor response (partial response or complete response at least 4 weeks apart).	Up to 2 years
Progression-free survival (PFS)	PFS is defined as the time from registration to the first of either disease progression or death from any cause.	Up to 2 years
Overall survival (OS)	OS is defined as the time from registration to death from any cause.	Up to 2 years
Incidence of adverse events (AEs)	The descriptions and grading scales found in the revised National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for AE reporting. The maximum grade for each type of AE will be recorded for each patient.	Up to 2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effects of plasma exchange on immune cell function		Up to 2 years
Kinetics of extracellular vesicles after plasma exchange in patients with melanoma	Will associate the kinetics with clinical outcome data (response rate, OS, PFS).	Up to 2 years

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Jacob J. Orme, M.D., Ph.D., Mayo Clinic in Rochester; Principal Investigator: Sean S. Park, M.D., Ph.D., Mayo Clinic in Rochester

Publications and helpful links

General Publications

• Davidson TM, Foster N, Lucien F, Markovic S, Dong H, Winters JL, Park SS, Orme JJ. Rescuing Cancer Immunity by Plasma Exchange in Metastatic Melanoma (ReCIPE-M1): protocol for a single-institution, open-label safety trial of plasma exchange to clear sPD-L1 for immunotherapy. BMJ Open. 2022 May 12;12(5):e050112. doi: 10.1136/bmjopen-2021-050112.

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2020
• Primary Completion (Actual): October 6, 2024
• Study Completion (Actual): October 6, 2024

Study Registration Dates

• First Submitted: September 18, 2020
• First Submitted That Met QC Criteria: October 5, 2020
• First Posted (Actual): October 9, 2020

Study Record Updates

• Last Update Posted (Actual): July 10, 2025
• Last Update Submitted That Met QC Criteria: July 7, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Melanoma; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Nivolumab; Pembrolizumab
• Other Study ID Numbers: MC200703 (Other Identifier: Mayo Clinic); NCI-2020-06970 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); R21CA259236 (U.S. NIH Grant/Contract); 20-003367 (Other Identifier: Mayo Clinic Institutional Review Board)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No