Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Allogeneic Peripheral Stem Cell Transplant After Antithymocyte Globulin, High-Dose Melphalan, and Fludarabine in Treating Women With Metastatic Adenocarcinoma of the Breast

Basic Trial Information

Objectives

Primary

1. 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.
2. Determine the ability of this preparative regimen to facilitate long-term engraftment of allogeneic stem cells and lymphocytes in these patients.
3. 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

1. Determine the progression-free and overall survival of patients treated with this regimen.
2. 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.
3. Determine the frequency and durability of the induction of full donor chimerism of lymphocytes in patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• Histologically confirmed adenocarcinoma of the breast
  • Metastatic disease
• Meets 1 of the following criteria:
  • Chemotherapy-unresponsive disease defined as 1 of the following:
    • Less than a partial response to 2 consecutive chemotherapy regimens that included an anthracycline and a taxane in combination or succession
    • Progression of disease during or within 3 months of completion of a taxane, anthracycline, or platinol-based regimen
  • Histologically confirmed tumor involvement on bone marrow biopsy
• Measurable or evaluable disease* defined as the following:
  • Bidimensionally reproducible measurable mass by physical examination, ultrasonography, radiography, CT scan, or MRI
  • Evaluable lesions apparent on clinical exam, x-ray, CT scan, or MRI which do not fit the criteria for measurability (e.g., ill-defined post-surgical masses or masses assessable in 1 dimension only)
    • Elevation of biological markers (e.g., CA 27.29) is considered evaluable disease

   [Note: *Bone lesions or pleural or peritoneal effusion alone are not considered measurable or evaluable disease]

• Appropriate candidate for allogeneic stem cell transplantation
• No active CNS metastases
• Available HLA-identical sibling donor
  • 6/6 antigen match
  • Donor CD34 cells at least 2 times 10⁶/kg recipient weight
• Hormone receptor status:
  • Estrogen receptor negative or positive
    • Estrogen receptor positive tumors must demonstrate progression on at least 1 hormonal manipulation

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• No concurrent glucocorticoids

Radiotherapy

• No prior radiotherapy to an indicator lesion unless the lesion shows evidence of progression after discontinuation of the therapy

Surgery

• Not specified

Other

• No concurrent immunosuppressive medication

Patient Characteristics:

Age

• 18 to 60

Sex

• Female

Menopausal status

• Not specified

Performance status

• Karnofsky 70-100%

  OR

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• WBC at least 1,500/mm³
• Platelet count at least 30,000/mm³

Hepatic

• Bilirubin less than 3 times normal*
• AST and ALT less than 3 times normal*

 [Note: *Unless abnormality due to malignancy]

Renal

• Creatinine no greater than 1.6 mg/dL

Cardiovascular

• LVEF greater than 40% by echocardiography or MUGA
• No myocardial infarction within the past 6 months

Pulmonary

• DLCO greater than 40% of predicted

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No serious localized or systemic infection
• No hypersensitivity to E. coli-derived products
• No history of non-breast malignant disease within the past 5 years except completely excised nonmelanoma skin cancer or carcinoma in situ of the cervix
• No chronic inflammatory disorder requiring concurrent glucocorticosteroids or other immunosuppressive medication
• No psychological condition or social situation that would preclude study participation

Expected Enrollment

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

Outcomes

Toxicity
Facilitation of long-term engraftment
Incidence and severity of acute and chronic graft-versus-host disease (GVHD)

Progression-free survival
Overall survival
Response (partial and complete) as measured at 1, 3, 6, and 12 months post allografting and within 1 week after the onset of documented GVHD if > 1 month separates any of the response evaluation timepoints
Frequency and durability of the induction of full donor chimerism of lymphocytes as measured at 1, 3, 6, and 12 months post allografting

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.

Trial Contact Information

Trial Lead Organizations

Rebecca and John Moores UCSD Cancer Center

Edward Ball, MD, Principal investigator		Ph: 858-822-6600

Registry Information
Official Title		Pilot Study Of Allogeneic Peripheral Blood Progenitor Cell Transplantation In Patients With Chemotherapy-Refractory Or Poor-Prognosis Metastatic Breast Cancer
Trial Start Date		2003-07-17
Trial Completion Date		2008-03-20
Registered in ClinicalTrials.gov		NCT00074269
Date Submitted to PDQ		2003-10-31
Information Last Verified		2008-04-10
NCI Grant/Contract Number		CA23100

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