Recruitment

Recruitment Status
Completed
Estimated Enrollment
107

Summary

Conditions
  • Breast Cancer
  • Cervical Cancer
  • Melanoma
  • Renal Cancer
  • Urothelial Cancer
Type
Interventional
Phase
Phase 1 & Phase 2
Design
  • Allocation: Non-Randomized
  • Intervention Model: Sequential Assignment
  • Masking: None (Open Label)
  • Primary Purpose: Treatment

Participation Requirements

Age
Between 18 years and 70 years
Gender
Both males and females

Description

Background: We have constructed a single retroviral vector that contains both and $ <= chains of a T cell receptor (TCR) that recognizes the DP0401/0402 restricted MAGE-A3 tumor antigen, which can be used to mediate genetic transfer of this TCR with high efficiency. In co-cultures with HLA-DP0401/04...

Background: We have constructed a single retroviral vector that contains both and $ <= chains of a T cell receptor (TCR) that recognizes the DP0401/0402 restricted MAGE-A3 tumor antigen, which can be used to mediate genetic transfer of this TCR with high efficiency. In co-cultures with HLA-DP0401/0402 and MAGE-A3 double positive tumors, the anti- MAGE-A3- DP0401/0402 restricted (anti-MAGE-A3-DP4) TCR transduced T cells secreted significant amounts of IFN-y with high specificity. Objectives: Primary objectives: Determine a safe dose of the administration of autologous CD4 cells transduced with an anti- MAGE-A3-DP0401/0402 restricted (MAGE-A3-DP4) TCR and aldesleukin to patients following a nonmyeloablative but lymphoid depleting preparative regimen. Determine if this approach will result in objective tumor regression in patients with metastatic cancer expressing MAGE-A3-DP4. Determine the toxicity profile of this treatment regimen. Eligibility: Patients who are HLA-DP0401/0402 positive and 18 years of age or older must have Metastatic cancer whose tumors express the MAGE-A3-DP4 antigen; Previously received and have been a non-responder to or recurred following at least one first line treatment for metastatic disease; Patients may not have: - Contraindications for high dose aldesleukin administration. Design: PBMC obtained by leukapheresis will be enriched for CD4 cells and transduced with the retroviral vector supernatant encoding the anti-MAGE-A3-DP4 TCR. The study will begin in a standard phase 1 dose escalation. After the MTD cell dose has been determined, patients will be enrolled into the phase 2 portion of the trial at the MTD established during the phase 1 portion of the study. In the phase 2 portion, patients will be entered into two cohorts: cohort 1 will include patients with metastatic melanoma; cohort 2 will include patients with renal cancer and other types of metastatic cancer. Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of ex vivo tumor reactive, TCR gene-transduced PBMC plus IV aldesleukin. Patients will undergo complete evaluation of tumor response every 1-6 months until off study criteria are met. For each of the 2 strata evaluated in the phase 2 portion, the study will be conducted using a phase 2 optimal design where initially 21 evaluable patients will be enrolled. For each of these two arms of the trial, if 0 or 1 of the 21 patients experiences a clinical response, then no further patients will be enrolled but if 2 or more of the first 21 evaluable patients enrolled have a clinical response, then accrual will continue until a total of 41 evaluable patients have been enrolled in that stratum. For both strata, the objective will be to determine if the treatment regimen is able to be associated with a clinical response rate that can rule out 5% (p0=0.05) in favor of a modest 20% PR + CR rate (p1=0.20).

Locations

Bethesda, Maryland, 20892
Bethesda, Maryland, 20892

Tracking Information

NCT #
NCT02111850
Collaborators
Not Provided
Investigators
  • Principal Investigator: Steven A Rosenberg, M.D. National Cancer Institute (NCI)
  • Steven A Rosenberg, M.D. National Cancer Institute (NCI)