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
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
Sponsors
Source
National Cancer Institute (NCI)
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.
Overall Status
Completed
Start Date
1996-05-01
Completion Date
2008-05-01
Primary Completion Date
2005-12-01
Phase
Phase 3
Study Type
Interventional
Condition
Intervention
Eligibility
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
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
Gender
Female
Minimum Age
18 Years
Maximum Age
65 Years
Healthy Volunteers
No
Overall Official
Last Name |
Role |
Affiliation |
|
Charles S. Hesdorffer, MD |
Study Chair |
Herbert Irving Comprehensive Cancer Center |
Location
Facility |
|
Herbert Irving Comprehensive Cancer Center New York New York 10032 United States |
Location Countries
Country
United States
Verification Date
2003-05-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Keywords
Has Expanded Access
No
Condition Browse
Secondary Id
CPMC-IRB-7608
CPMC-CAMP-014
NCI-G00-1890
Intervention Browse
Mesh Term
Interferons
Aldesleukin
Interferon-gamma
Cyclosporine
Cyclophosphamide
Thiotepa
Carboplatin
Cyclosporins
Results Reference
Citation
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. Epub 2007 Jun 11.
PMID
17563739
Firstreceived Results Date
N/A
Firstreceived Results Disposition Date
N/A
Study Design Info
Allocation
Randomized
Primary Purpose
Treatment
Study First Submitted
January 6, 2001
Study First Submitted Qc
June 4, 2003
Study First Posted
June 5, 2003
Last Update Submitted
February 1, 2013
Last Update Submitted Qc
February 1, 2013
Last Update Posted
February 4, 2013
ClinicalTrials.gov processed this data on December 06, 2019
Conditions
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conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.