T-Cell-Depleted Allogeneic Stem Cell Transplantation Followed By Donor T Cells, Given After Chemotherapy and Reduced-Intensity Transplantation Conditioning in Treating Patients With Metastatic Breast Cancer - Full Text View

Sponsor:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00082953

Purpose

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.

Condition	Intervention	Phase
Breast Cancer	Biological: filgrastim Biological: graft-versus-tumor induction therapy Biological: peripheral blood lymphocyte therapy Drug: cyclophosphamide Drug: cyclosporine Drug: fludarabine phosphate Procedure: peripheral blood stem cell transplantation	Phase I

Study Type:	Interventional
Study Design:	Treatment
Official Title:	Allogeneic Breast Protocol 2: Phase I Trial Of T Cell Exchange With Th2/Tc2 Cells For Allogeneic Stem Cell Transplantation After Reduced Intensity Conditioning For Metastatic Breast Cancer

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Cyclophosphamide Fludarabine Cyclosporine Fludarabine monophosphate Cyclosporin Filgrastim

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment:	45
Study Start Date:	March 2004
Estimated Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00082953

Locations

United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, United States, 20892-1182

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

Study Chair:

Michael R. Bishop, MD

National Cancer Institute (NCI)

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Featured trial article This link exits the ClinicalTrials.gov site

Publications:

Bishop MR. Nonmyeloablative allogeneic hematopoietic stem cell transplantation for metastatic breast cancer. Clin Breast Cancer. 2003 Apr;4(1):39-45. Review.

Jung U, Foley JE, Erdmann AA, Eckhaus MA, Fowler DH. CD3/CD28-costimulated T1 and T2 subsets: differential in vivo allosensitization generates distinct GVT and GVHD effects. Blood. 2003 Nov 1;102(9):3439-46. Epub 2003 Jul 10.

Study ID Numbers:	CDR0000361744, NCI-04-C-0131
Study First Received:	May 14, 2004
Last Updated:	August 12, 2009
ClinicalTrials.gov Identifier:	NCT00082953 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

stage IV breast cancer
recurrent breast cancer
male breast cancer

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Vidarabine
Antimetabolites, Antineoplastic
Cyclosporine
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Cyclophosphamide
Cyclosporins
Neoplasms by Site
Therapeutic Uses
Antifungal Agents
Dermatologic Agents

Alkylating Agents
Breast Diseases
Skin Diseases
Breast Neoplasms
Enzyme Inhibitors
Fludarabine monophosphate
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Myeloablative Agonists
Fludarabine
Antineoplastic Agents, Alkylating
Antirheumatic Agents

ClinicalTrials.gov processed this record on November 09, 2009