A Pilot Study Using Short-Term Cultured Anti-Tumor Autologous Lymphocytes

• Status: Active, not recruiting
• Trial end date: 2020-12-01
• Target enrollment: 0
• Participant gender: All

Summary

To determine the feasibility and safety of administering a regimen of TIL/IL-2, using a cell product manufactured in the Yale Advanced Cell Therapy Laboratories, in subjects with metastatic melanoma who are not responding or have progressed after receiving prior therapy with a PD-1/PD-L1 antagonist used alone or in combination with anti-CTLA-4. Additionally, a second cohort of patients with metastatic melanoma who are not responding or have progressed after receiving prior therapy with a PD-1/PD-L1 antagonist alone or in combination with anti-CTLA-4 will receive anti-PD-1 and anti-CTLA-4 therapy with Nivolumab and Ipilimumab.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Yale University
• Treatments: Ipilimumab; Nivolumab

Criteria

Inclusion Criteria:

For Cohorts 1 and 2:

• Metastatic melanoma;

• A metastatic lesion at least 1.5 cm in diameter that can be removed surgically

• Measurable or evaluable disease not including the resected lesion

• ECOG PS of 0 or 1 prior to cell harvest

• Assessment by the treating physician that ECOG performance status of no higher than 2 can be maintained at least for the period of cell generation, lymphoablation, cell infusion and IL-2 administration (for at least 6 weeks following cell harvest)

• Tumor refractory to or progressing following prior PD-1/PD-L1 therapy alone or in combination with an anti-CTLA-4 agent

• Ability to understand risks and benefits of the treatment and to give informed consent

Exclusion Criteria:

For Cohorts 1 and 2:

• Received prior cell transfer therapy that included non-myeloablative or ablative chemotherapy

• Any significant major organ dysfunction (see protocol)

• Residual toxicity > gr1 from immune checkpoint inhibitor other than persistent endocrinopathy on hormone replacement; all symptoms of prior colitis and enteritis must have resolved completely as assessed by history

• Any contraindication to neutropenia or thrombocytopenia for up to 2 weeks (no active major infection, no site of active, clinically significant bleeding)

• Concurrent major medical illnesses

• Any form of immunodeficiency

• Requirement for steroids > 10 mg prednisone daily or equivalent

• Severe hypersensitivity to any of the agents used in this study

• Contraindications for IL-2 administration

At the time of lymphoablation subjects must meet baseline eligibility criteria with the following additions and exceptions:

• Confirmation by lab that cell product can be ready for harvest and infusion within 7 days

For Cohort 2 only:

At the time of the start of anti-PD-1/anti-CTLA-4 therapy, subjects must meet baseline eligibility criteria with the following additions and exceptions:

• Patient cannot have a steroid requirement > 10 mg prednisone daily or equivalent

• Patients who have received prior PD-1/PD-L1 antagonist therapy and developed severe autoimmune disease precluding further immune checkpoint therapy

• Any organ dysfunction that makes the subject ineligible for anti-PD1 and anti-CTLA-4 treatment as deemed by the treating investigator

• ECOG PS of 0-2

• Hgb of at least 8.0 gm/dl (may be transfused to this level)

• Creatinine not greater than 2.5 mg/dl

• AST or ALT not > 5x ULN and total bilirubin not > 2.5 mg/dl

• No clinically significant change in major organ function compared to initial eligibility evaluation

• Prior to initiating the lymphoablation regimen, there can be no untreated brain lesion > 1.0 cm, and/or with significant evidence of hemorrhage. Subjects may begin lymphoablation no less than 1 full day after completing WBRT or stereotactic radiotherapy for brain lesions.