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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Edward Ball, University of California, San Diego
ClinicalTrials.gov Identifier:
NCT00074269
First received: December 10, 2003
Last updated: July 22, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Breast Cancer
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
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Study Of Allogeneic Peripheral Blood Progenitor Cell Transplantation In Patients With Chemotherapy-Refractory Or Poor-Prognosis Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by University of California, San Diego:

Primary Outcome Measures:
  • Toxicity [ Time Frame: period of the treatment ] [ Designated as safety issue: Yes ]
  • Facilitation of long-term engraftment [ Time Frame: post treatment ] [ Designated as safety issue: No ]
  • Incidence and severity of acute and chronic graft-versus-host disease (GVHD) [ Time Frame: post treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: post treatment ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: post treatment ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: post treatment ] [ Designated as safety issue: No ]
  • Frequency and durability of the induction of full donor chimerism of lymphocytes as measured at 1, 3, 6, and 12 months post allografting [ Time Frame: post treatment ] [ Designated as safety issue: No ]

Enrollment: 5
Study Start Date: July 2003
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: treatment 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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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 10^6/kg recipient weight
  • Hormone receptor status:

    • Estrogen receptor negative or positive

      • Estrogen receptor positive tumors must demonstrate progression on at least 1 hormonal manipulation

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/mm^3
  • Platelet count at least 30,000/mm^3

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00074269

Locations
United States, California
Rebecca and John Moores UCSD Cancer Center
La Jolla, California, United States, 92093-0658
Sponsors and Collaborators
University of California, San Diego
Investigators
Principal Investigator: Edward D. Ball, MD University of California, San Diego
  More Information

Additional Information:
No publications provided

Responsible Party: Edward Ball, MD, University of California, San Diego
ClinicalTrials.gov Identifier: NCT00074269     History of Changes
Other Study ID Numbers: UCSD-020815, CDR0000343758
Study First Received: December 10, 2003
Last Updated: July 22, 2013
Health Authority: United States: Federal Government

Keywords provided by University of California, San Diego:
recurrent breast cancer
stage IV breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Antilymphocyte Serum
Fludarabine
Fludarabine phosphate
Melphalan
Methotrexate
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Alkylating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 19, 2014