RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation or bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Biological therapy may interfere with the growth of the cancer cells. It is not yet known which post-transplant biological therapy regimen is more effective for breast cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of cyclosporine and interferon gamma to that of interleukin-2 following combination chemotherapy and bone marrow or peripheral stem cell transplantation in women who have stage II or stage III breast cancer.

Condition	Treatment or Intervention	Phase
stage IIIB breast cancer stage IIIA breast cancer stage II breast cancer	Procedure: chemotherapy  Procedure: biological response modifier therapy  Procedure: autologous bone marrow transplantation  Procedure: non-specific immune-modulator therapy  Procedure: interferon therapy  Procedure: bone marrow transplantation  Procedure: peripheral blood stem cell transplantation  Procedure: cytokine therapy  Procedure: interleukin therapy  Drug: bone marrow ablation with stem cell support  Drug: carboplatin  Drug: cyclophosphamide  Drug: cyclosporine  Drug: interferon gamma  Drug: interleukin-2  Drug: thiotepa	Phase III

Further Study Details: 

OBJECTIVES: I. Determine the response, disease-free survival (DFS), and overall survival of women with high-risk stage II or III breast cancer treated with high-dose cyclophosphamide, thiotepa, and carboplatin with autologous marrow and/or peripheral blood stem cell transplantation. II. Determine the safety of immunomodulation consisting of cyclosporine and interferon gamma versus low-dose interleukin-2 in this patient population. III. Determine parameters associated with immune activation and autologous graft-versus-host disease. IV. Determine which immunomodulation regimen is more efficacious with respect to DSF.

PROTOCOL OUTLINE: This is a randomized study. Patients are stratified according to stage (II vs III), age, lymph node status, and inflammatory histology. Patients are randomized to one of two immunomodulation arms. Autologous harvest of at least 1 million CD34+ cells /kg or 400 million mononuclear cells/kg must be achieved. All patients receive cyclophosphamide IV continuously and thiotepa IV continuously over 96 hours on days -6 through -3 and carboplatin IV over 5 hours daily on days -6 through -3. Patients undergo autologous bone marrow and/or peripheral blood stem cell transfusion on day 0. Arm I: Patients receive cyclosporine IV over 4 hours twice a day, beginning on day 0 and continuing until discharge from the hospital, and interferon gamma subcutaneously (SC) every 2 days on days 7-28. Arm II: Patients receive interleukin-2 SC daily for 28 days following recovery of blood counts. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 1 year and then annually for 5 years.

PROJECTED ACCRUAL: A total of 70 patients (30 with stage II disease and 40 with stage III disease) will be accrued over 2 years.

Ages Eligible for Study:  18 Years   -   65 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

Histologically confirmed breast cancer

• Stage II with at least 10 lymph nodes involved with malignancy OR
• Stage III (any T3b-T4, N2 or N3, M0)

Ineligible for other high priority national or institutional study

No metastasis to brain (confirmed by CT or MRI)

Hormone receptor status: Not specified

--Prior/Concurrent Therapy--

Biologic therapy: Not specified

Chemotherapy:

• At least 3 cycles of prior chemotherapy required
• Stage II patients must have completed 4-6 courses of doxorubicin and/or taxol-based adjuvant chemotherapy
• Stage III patients must have achieved complete or partial response to 4-6 courses of doxorubicin and/or taxol-based induction chemotherapy
• No other concurrent chemotherapy

Endocrine therapy: Not specified

Radiotherapy: Not specified

Surgery: Not specified

--Patient Characteristics--

Age: 18 to physiologic 65

Sex: Female

Menopausal status: Not specified

Performance status: ECOG 0-1

Life expectancy: Not specified

Hematopoietic: Not specified

Hepatic: Bilirubin less than 2 times normal

Renal: Creatinine less than 1.5 times normal

Cardiovascular: LVEF at least 45%

Other:

• HIV negative
• Not pregnant or nursing

New York
      Herbert Irving Comprehensive Cancer Center, New York,  New York,  10032,  United States

Study chairs or principal investigators

Charles S. Hesdorffer,  Study Chair,  Herbert Irving Comprehensive Cancer Center   

Study ID Numbers:  CDR0000068387; CPMC-IRB-7608; NCI-G00-1890; CPMC-CAMP-014
Record last reviewed:  June 2003
Last Updated:  October 13, 2004
Record first received:  January 6, 2001
ClinicalTrials.gov Identifier:  NCT00008203
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08