Expired Study
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Bethesda, Maryland 20892


RATIONALE: Drugs used in chemotherapy, such as fludarabine and cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Allogeneic stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy. Sometimes the transplanted cells can make an immune response against the body's normal tissues. Eliminating the T cells from the donor cells before transplanting them and giving cyclosporine may prevent this from happening. Infusing donor T cells that have been treated in the laboratory may be effective in killing metastatic tumor cells by making an immune response against the person's tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of laboratory-treated donor T cells when given after chemotherapy, reduced-intensity transplantation conditioning (chemotherapy given before the transplant in doses that will not destroy all bone marrow cells), and T cell-depleted (T cells removed) donor stem cell transplantation in treating patients with metastatic breast cancer.

Study summary:

OBJECTIVES: Primary - Determine the safety, in terms of the incidence of acute graft-versus-host disease, and feasibility of using in vitro-generated donor T cells of Th2/Tc2 phenotype to augment a T-cell-depleted allogeneic stem cell transplantation after immunoablative induction chemotherapy and reduced-intensity transplantation conditioning in patients with metastatic breast cancer. Secondary - Determine the effect of this treatment regimen on donor chimerism in these patients. - Determine the effect of this treatment regimen on clinical response in these patients. - Determine the progression-free and overall survival of patients treated with this regimen. OUTLINE: This is a dose-escalation study of Th2/Tc2 cells. - Immunoablative induction chemotherapy: Patients receive fludarabine IV over 30 minutes and cyclophosphamide IV over 2 hours on days 1-4. Patients also receive filgrastim (G-CSF) subcutaneously (SC) beginning on day 5 and continuing until blood counts recover. In order to achieve the greatest immunosuppression before transplantation, patients may receive a second course of immunoablative induction chemotherapy beginning on day 21 depending on CD4+ count. - Transplantation preparative regimen: Beginning 7-21 days after recovery from induction chemotherapy, patients receive fludarabine IV over 30 minutes and cyclophosphamide IV over 2 hours on days -6 to -3 before transplantation. - Graft-versus-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV over 2 hours or orally every 12 hours beginning on day -1 and continuing until day 28, followed by a taper until day 40. - Allogeneic stem cell transplantation (SCT): Patients undergo T-cell-depleted allogeneic peripheral blood SCT on day 0. Patients receive G-CSF SC beginning on day 0 and continuing until blood counts recover. - Donor Th2/Tc2 cell administration: Patients receive donor Th2/Tc2 cells IV on day 0 after SCT. Cohorts of 6-12 patients receive escalating doses of donor Th2/Tc2 cells until feasibility is determined. Feasibility is defined as the dose level at which no more than 6 of 12 patients experience grade II-IV acute GVHD by day 42 post-transplantation. - Donor lymphocyte infusion (DLI): Patients with progressive malignant disease and less than grade II acute GVHD at day 42 post-transplantation may receive DLI on days 42, 70, and 98. Patients are followed every 2 weeks until approximately day 100 and then at 6, 9, 12, 18 and 24 months. PROJECTED ACCRUAL: A total of 45 patients will be accrued for this study within 2-3 years.


DISEASE CHARACTERISTICS: - Diagnosis of stage IV breast cancer - Measurable disease - Received at least 1 prior chemotherapy regimen for treatment of distant metastases and achieved less than a complete response - Must have received prior therapy with a taxane (e.g., paclitaxel) and an anthracycline (e.g., doxorubicin) either as adjuvant therapy or as treatment of metastatic disease - If tumor expresses Her2-neu, patient must have received trastuzumab (Herceptin®) in either the adjuvant or metastatic setting - If tumor expresses estrogen and/or progesterone receptors, patient must have received at least 1 hormonal therapy (e.g., tamoxifen) in either the adjuvant or metastatic setting - CNS metastases allowed if treated and stable for at least 4 weeks after completion of therapy - Consenting sibling donor with 6 of 6 matching HLA antigens - Hormone receptor status: - Not specified PATIENT CHARACTERISTICS: Age - 18 to 75 Sex - Not specified Menopausal status - Not specified Performance status - ECOG 0-2 OR - Karnofsky 60-100% Life expectancy - More than 6 months Hematopoietic - Not specified Hepatic - Bilirubin ≤ 2.5 mg/dL* - SGOT < 4 times upper limit of normal* - Hepatitis B surface antigen negative - Hepatitis C antibody negative NOTE: *Unless due to liver involvement by malignancy Renal - Creatinine ≤ 1.5 mg/dL - Creatinine clearance ≥ 50 mL/min Cardiovascular - LVEF ≥ 45% by MUGA or 2-dimensional echocardiogram Pulmonary - DLCO ≥ 50% of expected value (corrected for hemoglobin) Other - HIV negative - No active infection that does not respond to antimicrobial therapy - No history of a psychiatric disorder that would preclude study compliance - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for at least 1 year after study participation PRIOR CONCURRENT THERAPY: Biologic therapy - See Disease Characteristics - Prior autologous stem cell transplantation allowed Chemotherapy - See Disease Characteristics Endocrine therapy - See Disease Characteristics Radiotherapy - Not specified Surgery - Not specified



Primary Contact:

Study Chair
Michael R. Bishop, MD
National Cancer Institute (NCI)

Backup Contact:


Location Contact:

Bethesda, Maryland 20892
United States

There is no listed contact information for this specific location.

Site Status: N/A

Data Source: ClinicalTrials.gov

Date Processed: October 09, 2019

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