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

NCT00074269 | Terminated Phase 2 Results DMC

• 2 other identifiers: 020815CDR0000343758
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer

Keywords

recurrent breast cancer; stage IV breast cancer

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Adverse Events

  5 years post transplant

• Number of Participants With Long-term Engraftment of Allogeneic Stem Cells and Lymphocytes

  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

  30 days post transplant

• Number of Participants With Acute and Chronic Graft-versus-host Disease (GVHD)

  100 days post transplant

Secondary Outcomes (4)

• 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

• 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

• Frequency of the Induction of Full Donor Chimerism of Lymphocytes as Measured at 1 Month Post Allografting

  1 month post allografting

Study Arms (1)

treatment

EXPERIMENTAL

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

Interventions

anti-thymocyte globulin BIOLOGICAL

treatment

filgrastim BIOLOGICAL

treatment

graft-versus-tumor induction therapy BIOLOGICAL

treatment

therapeutic allogeneic lymphocytes BIOLOGICAL

treatment

cyclosporine DRUG

treatment

fludarabine phosphate DRUG

treatment

melphalan DRUG

treatment

methotrexate DRUG

treatment

peripheral blood stem cell transplantation PROCEDURE

treatment

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of California, San Diego: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Rebecca and John Moores UCSD Cancer Center

La Jolla, California, 92093-0658, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Antilymphocyte Serum; Filgrastim; Cyclosporine; fludarabine phosphate; Melphalan; Methotrexate; Peripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Limitations and Caveats

Terminated early due to small numbers of subjects enrolled on study

Results Point of Contact

• Title: Dr. Edward Ball, Director BMT Program
• Organization: UCSD

tball@ucsd.edu

858-822-6600

Study Officials

• Edward D. Ball, MD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: December 10, 2003
• First Posted: December 11, 2003
• Study Start: July 1, 2003
• Primary Completion: March 1, 2008
• Study Completion: March 1, 2008
• Last Updated: June 5, 2023
• Results First Posted: November 24, 2014

Record last verified: 2023-05

Locations

US (1)