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

Alternate Title

Comparison of Biological Therapies Following Combination Chemotherapy and Bone Marrow or Peripheral Stem Cell Transplantation in Women With Stage II or Stage III Breast Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Completed	18 to physiologic 65	NCI	CPMC-IRB-7608 CPMC-CAMP-014, NCI-G00-1890, NCT00008203

Objectives

1. 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.
2. Determine the safety of immunomodulation consisting of cyclosporine and interferon gamma versus low-dose interleukin-2 in this patient population.
3. Determine parameters associated with immune activation and autologous graft-versus-host disease.
4. Determine which immunomodulation regimen is more efficacious with respect to DSF.

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

Expected Enrollment

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

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.

Cohen DJ, Vahdat LT, Zipin D, et al.: Randomized trial of low-dose interleukin-2 vs. cyclosporine A and interferon- after high dose chemotherapy with peripheral blood progenitor support in women with high risk primary breast cancer (HRPBC). [Abstract] Breast Cancer Res Treat 88 (1): A-2079, 2004.

Trial Contact Information

Trial Lead Organizations

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

Charles Hesdorffer, MD, Protocol chair		Ph: 212-305-4907 Email: csh1@columbia.edu

Registry Information
Official Title		High-Dose Chemotherapy Followed By Autologous Hematopoietic Stem Cell Support And One Of Two Regimens Aimed At Modifying Immune Reconstitution In Women With High Risk Stage 2 And Stage 3 Breast Cancer
Trial Start Date		1996-05-14
Trial Completion Date		2005-12-01
Registered in ClinicalTrials.gov		NCT00008203
Date Submitted to PDQ		2000-11-21
Information Last Verified		2003-05-06
NCI Grant/Contract Number		CA13696