Treated Blood Cells, Cyclophosphamide, Fludarabine Phosphate, and Aldesleukin in Treating Patients With Cancer

Phase 1

Terminated

• Conditions: Breast Cancer; Colorectal Cancer; Gastric Cancer; Lung Cancer; Ovarian Cancer; Pancreatic Cancer; Unspecified Adult Solid Tumor, Protocol Specific

• Registration Number: NCT01212887
• Lead Sponsor: Cancer Research UK

Brief Summary

RATIONALE: Placing a gene into T cells may improve the body's ability to recognize cancer cells and build an immune response to fight cancer. Drugs used in chemotherapy, such as cyclophosphamide and fludarabine phosphate, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Biological therapies, such as aldesleukin, may stimulate the immune system in different ways and stop cancer cells from growing. Giving specially treated T cells together with cyclophosphamide, fludarabine phosphate, and aldesleukin may kill more tumor cells.

PURPOSE: This phase I clinical trial is studying the side effects and best dose of treated T cells when given together with cyclophosphamide, fludarabine phosphate, and aldesleukin in treating patients with cancer.

Detailed Description

OBJECTIVES:

Primary

* To evaluate the feasibility of MFE23 scFv-expressing autologous anti-CEA MFEz T lymphocytes in combination with preconditioning chemotherapy comprising cyclophosphamide and fludarabine phosphate plus aldesleukin in patients with CEA-positive tumors.

* To assess the toxicity of this regimen in these patients.

* To determine the dose of MFE23 scFv-expressing autologous anti-CEA MFEz T lymphocytes required to give optimal survival of these cells in the circulation (recommended phase II dose).

Secondary

* To assess whether MFE23 scFv-expressing autologous anti-CEA MFEz T lymphocytes isolated from the circulation are functional.

* To determine the preliminary tumor response to MFE23 scFv-expressing autologous anti-CEA MFEz T lymphocytes.

* To evaluate the safety of MFE23 scFv-expressing autologous anti-CEA MFEz T lymphocytes.

OUTLINE: This is a phase I, dose-escalation study of MFE23 scFv-expressing autologous anti-CEA MFEz T lymphocytes.

Patients undergo leukapheresis 7-14 days before study therapy begins. Cells are then transduced with a retrovirus vector and expanded to produce MFE23 scFv-expressing autologous anti-CEA MFEz T lymphocytes.

Patients receive preconditioning chemotherapy comprising fludarabine phosphate IV over 15 minutes on days -5 to -1 or cyclophosphamide IV over 1 hour on days -7 to -6 and fludarabine phosphate IV over 15 minutes on days -5 to -1. They receive MFE23 scFv-expressing autologous anti-CEA MFEz T lymphocytes IV over 30 minutes on day 0. Patients also receive high-dose aldesleukin IV over 15 minutes every 8 hours for up to 12 doses beginning on day 0, in the absence of disease progression or unacceptable toxicity. If there is evidence of MFE23 scFv-expressing autologous anti-CEA MFEz T lymphocytes survival, patients may receive additional high-dose aldesleukin.

Patients undergo blood sample collection periodically for pharmacokinetic and pharmacodynamic studies. Some patients may undergo a tumor biopsy.

After completion of study treatment, patients are followed up every 2 weeks for 6 weeks, every 4 weeks for 6 months, every 3 months for 1 year, and then every 6 months thereafter.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

Study Timeline

• Study Start: 2007-08
• Primary Completion: 2010-04
• Study Completion: 2010-04
• Study First Submitted: 2010-09-30
• Study First Submitted QC: 2010-09-30
• Study First Posted: 2010-10-01
• Status Verified: 2012-02
• Last Update Submitted: 2012-02-27
• Last Update Posted: 2012-02-28

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 14

Inclusion Criteria

Not provided

Read More

Exclusion Criteria

Not provided

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Percentage of patients (goal is 50%) who are evaluable for MFE23 scFv-expressing autologous anti-CEA MFEz T lymphocytes survival
Adverse event according to CTCAE version 3 criteria
Dose of MFE23 scFv-expressing autologous anti-CEA MFEz T lymphocytes that gives the highest frequency in the circulation as measured by the primary assays (recommended phase II dose)

Secondary Outcome Measures

Name	Time	Method
Presence of cells with a functional chimeric immune receptor on bCEA binding assay
Partial response or complete response on CT scans at 6, 12, 24, and 52 weeks as defined by RECIST criteria
Long-term follow up for insertional mutagenesis

Trial Locations

Locations (1)

Christie Hospital; 🇬🇧 Manchester, England, United Kingdom