Single Patient Protocol: A Phase II Study Using the Administration of Autologous T-Cells Genetically Engineered to Express T-Cell Receptors Reactive Against Mutated Neoantigens in a Patient With Metastatic Cancer Plus the Administration of Pembrolizumab

NCT ID: NCT04135092

Last Updated: 2020-09-04

Basic Information

• Recruitment Status: NO_LONGER_AVAILABLE
• Study Classification: EXPANDED_ACCESS

Brief Summary

Single Patient Expanded Access

Detailed Description

Background:

Please refer to National Cancer Institute Surgery Branch (NCI-SB) protocol 18-C-0049, Amendment F.

Objective:

Under Individual Patient Expanded Access, to treat a patient with metastatic prostate cancer with autologous peripheral blood lymphocytes (PBL) that have been transduced with genes encoding T-cell receptors that recognize the mutated TP53 shared oncogene in the autologous cancer.

Eligibility:

• Must have measurable, metastatic disease as assessed per RECIST v1.1 criteria.
• Must sign the informed consent document.
• Willing to sign Durable Power of Attorney Form.
• Must have all regulatory approvals prior to start of treatment.

Design:

• Please refer to NCI-SB protocol 18-C-0049, Amendment F.
• The patient will be treated with a non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine, followed by the infusion of autologous transduced PBL and then high-dose aldesleukin. The patient will also receive pembrolizumab on Day -2 prior to cell administration and additional doses every 3 weeks following cell infusion until the time of disease progression.

Interventions

Individual Patient TCR Transduced PBL

Day 0: Cells will be infused at a dose not to exceed .5e11 in 400 mL IV on the Patient Care Unit over 20-30 minutes (2-4 days after the last dose of fludarabine).

Intervention Type: BIOLOGICAL

Cyclophosphamide

Days -7 and -6: Cyclophosphamide 60 mg/kg/day x 2 days IV in 250 mL D5W infused simultaneously with mesna 15 mg/kg/day over 1 hour x 2 days.

Intervention Type: DRUG

Fludarabine

Days -7 to -3: Fludarabine 25 mg/m2 /day IVPB daily over 30 minutes for 5 days.

Intervention Type: DRUG

Aldesleukin

Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 10 doses).

Intervention Type: DRUG

Pembrolizumab

Pembrolizumab 2 mg /kg IV over approximately 30 minutes on Day -2 and then every 3 weeks until time of disease progression.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Measurable (per RECIST v1.1 criteria), metastatic prostate cancer.
• Refractory to approved standard systemic therapy.
• Ability of subject to understand and the willingness to sign a written informed consent document.
• Willing to sign a Durable Power of Attorney Form.
• Willing to practice birth control from the time of enrollment on this study and for four months after treatment.
• Subject must be co-enrolled on protocol 03-C-0277.

Exclusion Criteria

Not applicable.

• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health Clinical Center (CC)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Other Identifiers

209950

Identifier Type: -

Identifier Source: org_study_id