Cellular Adoptive Immunotherapy in Treating a Patient Who Has Undergone a Donor Stem Cell Transplant for Breast Cancer That Has Spread to the Lung

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00301730

Collaborator

(none)

Enrollment

Location

Study Details

Study Description

Brief Summary

RATIONALE: Biological therapy, such as cellular adoptive immunotherapy, may stimulate the immune system in different ways and stop tumor cells from growing.

PURPOSE: This phase I trial is studying how well cellular adoptive immunotherapy works in treating a patient who has undergone a donor stem cell transplant for breast cancer that has spread to the lung.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Metastatic Cancer	Biological: aldesleukin Biological: therapeutic tumor infiltrating lymphocytes Biological: trastuzumab Drug: paclitaxel Procedure: conventional surgery	Phase 1

Detailed Description

OBJECTIVES:

Primary

Determine the antitumor response in a patient with persistent metastatic breast cancer after prior allogeneic hematopoietic stem cell transplantation (SCT) treated with tumor-derived, ex vivo expanded and costimulated T-lymphocytes.

Secondary

Evaluate the immune function of tumor-derived T-lymphocytes and the biology of residual tumor cells present after allogeneic hematopoietic SCT.

OUTLINE: This is a pilot study.

The patient undergoes surgical resection of the accessible lesions from which T cells are isolated, costimulated, and expanded ex vivo to produce the tumor-derived T-lymphocytes (TDTL). Beginning at least 2 weeks after surgery, the patient receives TDTL IV every 4 weeks for up to 5 doses in the presence of disease progression (DP) AND in the absence of ≥ grade 2 graft-versus-host disease. The patient is assessed 4 weeks after every dose.

In case of stable disease, partial response, or complete response, the patient is followed without intervention until DP.

In case of DP after dose 1 or 2 of the TDTL, the patient receives dose 2 or 3 of the TDTL. In case of DP after dose 3 of the TDTL, the patient receives low-dose interleukin-2 subcutaneously (SC) daily for 3 days and dose 4 of the TDTL. In case of DP after dose 4 of the TDTL, the patient receives 1 course of chemoimmunotherapy for cytoreduction and immunomodulation comprising paclitaxel IV over 3 hours once and trastuzumab (Herceptin®) IV over 30-90 minutes once weekly for 3 weeks (the patient may receive gemcitabine hydrochloride, vinorelbine ditartrate, docetaxel, or capecitabine in combination with trastuzumab [Herceptin®] as chemoimmunotherapy at the discretion of the principal investigator); interleukin-2 SC daily for 3 days; and dose 5 of the TDTL. In case of DP after dose 5 of the TDTL, the patient may receive cytotoxic chemotherapy and/or FDA-approved biologic therapy and/or immunotherapy with donor lymphocyte infusions from the same donor used for the prior allogeneic stem cell transplantation.

The patient may undergo core biopsy of the left mediastinal nodule in case of tumor regression of the indexing lesion at anytime OR after receiving dose 5 of the TDTL.

After completion of study treatment, the patient is followed periodically for 5 years.

PROJECTED ACCRUAL: One patient will be accrued for this study.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1 participants

Primary Purpose:

Treatment

Official Title:

Adoptive Immunotherapy With Costimulated Tumor-Derived T Cells After Allogeneic Hematopoietic Stem Cell Transplantation

Study Start Date :

Oct 1, 2005

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Diagnosis of stage IIB HER2/neu-expressing breast cancer 6½ years ago
Received a T-cell-depleted allogeneic stem cell transplantation (SCT) from a 6/6 HLA-matched sibling donor for refractory metastatic breast cancer
Developed pulmonary metastases during adjuvant chemotherapy following modified radical mastectomy
Pulmonary metastases progressed after prior allogeneic SCT
Responded in an objective and measurable manner to prior allogeneic lymphocyte infusion, post-transplantation chemotherapy, and trastuzumab (Herceptin®)
Disease limited to the thoracic cavity
Operable tumor with at least 1 cm of surgically accessible lesion
Preoperative risk assessment indicating ≤ 5% risk of mortality and < 15% risk of significant morbidity for pulmonary metastasectomy
Enrolled on protocol CC# 00-C-0119
Hormone receptor status not specified

PATIENT CHARACTERISTICS:

Female
Menopausal status not specified
ECOG performance status 0-2
Life expectancy > 6 months
Negative pregnancy test
Adequate pulmonary reserve
Prior graft-versus-host disease (GVHD) ≤ grade 1
No concurrent GVHD
No active infection nonresponsive to antimicrobial therapy
No active psychiatric disorder that would preclude study compliance

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
At least 4 weeks since prior systemic immunosuppressive therapy
At least 2 weeks since prior cytotoxic therapy and immunotherapy (e.g. trastuzumab [Herceptin®])
No concurrent immunosuppressive therapy