Allogeneic Stem Cell Transplant After ATG, High-Dose Melphalan, and Fludarabine for Patients With Breast Cancer

Phase 2

Terminated

Conditions: Breast Cancer

Interventions: Biological: anti-thymocyte globulin
Biological: filgrastim
Biological: graft-versus-tumor induction therapy
Biological: therapeutic allogeneic lymphocytes
Drug: cyclosporine
Drug: fludarabine phosphate
Drug: melphalan
Drug: methotrexate
Procedure: peripheral blood stem cell transplantation

Registration Number: NCT00074269

Lead Sponsor: University of California, San Diego

Brief Summary: RATIONALE: Giving chemotherapy, such as fludarabine and melphalan, before a donor peripheral blood stem cell transplant helps stop the growth of tumor cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining tumor cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving antithymocyte globulin, cyclosporine, and methotrexate before or after the transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well antithymocyte globulin, high-dose melphalan, fludarabine, and allogeneic peripheral stem cell transplant work in treating patients with metastatic adenocarcinoma of the breast.

Detailed Description: OBJECTIVES:

Primary

* Determine the toxicity and tolerability of allogeneic peripheral blood stem cell transplantation after a nonmyeloablative preparative regimen comprising anti-thymocyte globulin, high-dose melphalan, and fludarabine in women with chemotherapy-refractory or poor-prognosis metastatic adenocarcinoma of the breast.

* Determine the ability of this preparative regimen to facilitate long-term engraftment of allogeneic stem cells and lymphocytes in these patients.

* Determine the response in measurable/evaluable disease and its temporal relationship to the preparative chemotherapy used and to the onset of clinical graft-versus-host disease (GVHD) in patients treated with this regimen.

Secondary

* Determine the progression-free and overall survival of patients treated with this regimen.

* Determine the tumor response and its temporal relationship to administration of high-dose chemotherapy and to the onset of GVHD in patients treated with this regimen.

* Determine the frequency and durability of the induction of full donor chimerism of lymphocytes in patients treated with this regimen.

OUTLINE: This is a nonrandomized, pilot study.

* Nonmyeloablative preparative regimen: Patients receive fludarabine IV over 30 minutes on days -8 to -4, anti-thymocyte globulin IV over 4 hours on days -7 to -4, and high-dose melphalan IV over 30 minutes on days -3 and -2.

* Graft-versus-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV (and then orally when tolerated) every 12 hours beginning on day -4 and tapered after day 42 (if no GVHD occurs) or after day 90 (if grade I acute GVHD occurs). Patients also receive methotrexate IV on days 1, 3, and 6.

* Allogeneic peripheral blood stem cell transplantation (PBSCT): Patients undergo allogeneic PBSCT on day 0. Patients also receive filgrastim (G-CSF) IV or subcutaneously beginning on day 0 and continuing until blood counts recover.

* Donor lymphocyte infusion (DLI): Patients who show disease progression or fail to achieve full donor type T-cell chimerism (at least 90% donor derived T-cells) by the 90-day assessment posttransplantation, and have no evidence of active GVHD may receive DLI. Patients who have unresponsive disease with no active GVHD receive subsequent DLIs every 6-8 weeks.

Patients are followed at 1, 3, 6, 12, 18, 24, 30, and 36 months.

PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study.

Recruitment & Eligibility

Status: TERMINATED

Sex: Female

Target Recruitment: 5

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
treatment	melphalan	-
treatment	methotrexate	-
treatment	peripheral blood stem cell transplantation	-
treatment	graft-versus-tumor induction therapy	-
treatment	therapeutic allogeneic lymphocytes	-
treatment	anti-thymocyte globulin	-
treatment	filgrastim	-
treatment	fludarabine phosphate	-
treatment	cyclosporine	-

Primary Outcome Measures

Name	Time	Method
Number of Participants With Acute and Chronic Graft-versus-host Disease (GVHD)	100 days post transplant
Number of Participants With Long-term Engraftment of Allogeneic Stem Cells and Lymphocytes	30 days post transplant	Long-term Engraftment of Allogeneic Stem Cells and Lymphocytes based on cell counts of ANC \>1000 for 3 consecutive days and platelet count of \>50,000
Number of Participants With Adverse Events	5 years post transplant

Secondary Outcome Measures

Name	Time	Method
Progression-free Survival	From date of transplant until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months	Progression assessed by CT scan
Overall Survival	1 year from the time of transplant
Response as Measured at 12 Months Post Allografting	From date of transplant until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months	response (partial and complete) assessed by CT scan at 12 months post allografting
Frequency of the Induction of Full Donor Chimerism of Lymphocytes as Measured at 1 Month Post Allografting	1 month post allografting