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

NCT ID: NCT00008203

Last Updated: 2013-02-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 1996-05-31
• Study Completion Date: 2008-05-31

Brief Summary

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.

Detailed Description

OBJECTIVES:

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

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: TREATMENT

Interventions

aldesleukin

Intervention Type: BIOLOGICAL

recombinant interferon gamma

Intervention Type: BIOLOGICAL

carboplatin

Intervention Type: DRUG

cyclophosphamide

Intervention Type: DRUG

cyclosporine

Intervention Type: DRUG

thiotepa

Intervention Type: DRUG

autologous bone marrow transplantation

Intervention Type: PROCEDURE

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• No metastasis to brain (confirmed by CT or MRI)
• Hormone receptor status:

• 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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Herbert Irving Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Principal Investigators

Charles S. Hesdorffer, MD

Role: STUDY_CHAIR

Herbert Irving Comprehensive Cancer Center

Locations

Herbert Irving Comprehensive Cancer Center

New York, New York, United States

Countries

United States

References

Vahdat LT, Cohen DJ, Zipin D, Lo KS, Donovan D, Savage D, Tiersten A, Nichols G, Troxel A, Hesdorffer CS. Randomized trial of low-dose interleukin-2 vs cyclosporine A and interferon-gamma after high-dose chemotherapy with peripheral blood progenitor support in women with high-risk primary breast cancer. Bone Marrow Transplant. 2007 Aug;40(3):267-72. doi: 10.1038/sj.bmt.1705692. Epub 2007 Jun 11.

Reference Type: RESULT

PMID: 17563739 (View on PubMed)

Other Identifiers

CPMC-IRB-7608

Identifier Type: -

Identifier Source: secondary_id

CPMC-CAMP-014

Identifier Type: -

Identifier Source: secondary_id

NCI-G00-1890

Identifier Type: -

Identifier Source: secondary_id

CDR0000068387

Identifier Type: -

Identifier Source: org_study_id