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Combination Chemotherapy and Peripheral Blood Stem Cell Transplant Followed By Aldesleukin and Sargramostim in Treating Patients With Inflammatory Stage IIIB or Metastatic Stage IV Breast Cancer

Primary Purpose

Estrogen Receptor-negative Breast Cancer, Estrogen Receptor-positive Breast Cancer, Inflammatory Breast Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
tamoxifen citrate
busulfan
thiotepa
melphalan
aldesleukin
sargramostim
peripheral blood stem cell transplantation
radiation therapy
Sponsored by
Fred Hutchinson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Estrogen Receptor-negative Breast Cancer

Eligibility Criteria

19 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients with inflammatory (stage IIIb) or responsive stage IV breast cancer with metastasis to soft tissue and/or bone; responsive stage IV disease is defined as patients who achieve a PR (>= 50% reduction in measurable tumor burden) or CR following initial chemotherapy for metastatic disease or patients with locally recurrent disease (chest wall/axillary nodes) who are rendered disease-free following surgery or radiation therapy without receiving chemotherapy; bone disease is categorized as responsive if there is demonstrated sclerosis of prior lesions with no new lesions Patients should have received 4-7 cycles of an Adriamycin and/or taxane-based regimen for stage IIIb or stage IV disease; locally recurrent (chest wall/axillary nodes) patients rendered NED by RT or surgery do not need to receive chemotherapy for stage IV disease prior to Cytoxan/Taxol Patient has received Cytoxan 4 gm/m^2 x 1 and Taxol 250 mg/m^2 x 1 per FHCRC protocol 506.03; Cytoxan/Taxol must be given after all other chemotherapy is completed and before transplant Stem cells were collected after mobilization with Cytoxan/Taxol or after mobilization from an FHCRC approved cytokine protocol; if syngeneic collection, PBSC's were collected by using G-CSF according to FHCRC protocol 753; patient has an adequate number of peripheral blood stem cells stored (>= 2.5 x 10^6 CD34+ cells/kg) The patient must have the capacity to give informed consent; the patient must have signed an approved consent form conforming with federal and institutional guidelines Hepatic function: Bilirubin =< 2 mg%; SGOT or SGPT =< 2.5 x institutional normal Renal function: Creatinine =< 2.0 mg/dl or a creatinine clearance >= 50 mg/min Pre-Study tests have been performed as outlined in the Study Calendar Patients will begin IL-2/GM-CSF therapy if they meet the following criteria post-transplant: Can start therapy 30 to 100 days after transplant Karnofsky performance status > 60 ANC > 1,000 cells/mm^3 and platelets > 30,000/cells/mm^3 (transfusion independent) for at least 5 days before starting therapy Total bilirubin =< 2.5 x upper limit of normal SGOT =< 2.5 x upper limit of normal Creatinine =< 2.0 mg/dl Exclusion Criteria: Patients with a Karnofsky Performance Score less than 70 Patients with a left ventricular ejection fraction less than 50 % (LVEF must be performed in patients with symptoms of CHF, abnormal cardiac exam or history of Adriamycin therapy total dose > 400 mg/m^2) Patient is pregnant Patient is seropositive for the human immunodeficiency virus Patients with a history of seizures Patients with hypersensitivity to E.coli preparations Patients with active auto-immune disease Patients with clinically significant pulmonary disease, i.e., diffusion capacity corrected < 60% of predicted; patients with pulmonary problems should be evaluated with appropriate pulmonary studies and/or consult Patients with a history of CNS lesion (brain or carcinoid meningitis) Patients with significant active infection precluding transplant Patients who have had more than one prior chemotherapy regimen for stage IV disease or a prior transplant for any stage disease Patients who have had CD34+ selection of their PBSC products Patients will not receive IL-2/GM-CSF therapy if they: Are > 100 days from transplant Have documented disease progression after transplant Have an active infection Manifested cardiac complications during the initial transplant period, including arrhythmias (that required therapy), congestive heart failure, angina, myocardial infarct, or decreased LVEF to < 45% Currently have pericardial effusions, pleural effusions or ascites Manifested pulmonary toxicity during the initial transplant period and have a diffusion capacity corrected =< 60% Are on steroids Currently have a Grade 3 toxicity from BuMelTT If the patient does not wish to receive the therapy

Sites / Locations

  • Fred Hutchinson Cancer Research Center/Puget Sound Oncology Consortium

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm I

Arm Description

See Detailed Description.

Outcomes

Primary Outcome Measures

Event-free Survival
Event-free survival of patients treated for inflammatory (Stage IIIb) and responsive stage IV breast cancer with BUMELTT and PBSC support and low dose immunotherapy with IL2 and GM-CSF.

Secondary Outcome Measures

Overall Survival
Overall survival of patients treated for inflammatory (Stage IIIb) and responsive stage IV breast cancer with BUMELTT and PBSC support and low dose immunotherapy with IL2 and GM-CSF.
Number of Participants With Toxicity of a Combination of Low-dose IL-2 and GM-CSF
IL-2/GM-CSF toxicity assessed using the NCI Toxicity Criteria. Toxicity was defined as any grade 2, 3, 4 or 5 CNS (except grade 0-3 malaise and fatigue) toxicity; any grade 3, 4, or 5 non-CNS or non-hematological toxicity (except grade 0-3 bilirubin); or any grade 4 or 5 hematological toxicity.

Full Information

First Posted
November 1, 1999
Last Updated
June 16, 2017
Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00003199
Brief Title
Combination Chemotherapy and Peripheral Blood Stem Cell Transplant Followed By Aldesleukin and Sargramostim in Treating Patients With Inflammatory Stage IIIB or Metastatic Stage IV Breast Cancer
Official Title
A Phase II Trial for Patients With Inflammatory (Stage IIIB) and Responsive Metastatic Stage IV Breast Cancer Using Busulfan, Melphalan and Thiotepa Followed by Autologous or Syngeneic PBSC Rescue and 12 Weeks of Post-Engraftment Immunotherapy With Low-Dose IL-2 and GM-CSF
Study Type
Interventional

2. Study Status

Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
November 1997 (Actual)
Primary Completion Date
December 2009 (Actual)
Study Completion Date
December 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This phase II trial studies how well giving combination chemotherapy and peripheral blood stem cell transplant followed by aldesleukin and sargramostim works in treating patients with inflammatory stage IIIB or metastatic stage IV breast cancer. Drugs used in chemotherapy, such as busulfan, melphalan, and thiotepa, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. A peripheral stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy. This may allow more chemotherapy to be given so that more tumor cells are killed. Aldesleukin may stimulate the white blood cells to kill breast cancer cells. Giving aldesleukin together with sargramostim may kill more tumor cells
Detailed Description
PRIMARY OBJECTIVES: I. To determine the event-free survival and survival of patients treated for inflammatory (Stage IIIb) and responsive stage IV breast cancer with BUMELTT and PBSC support and low dose immunotherapy with IL2 and GM-CSF. SECONDARY OBJECTIVES: II. To determine the toxicity of a combination of low-dose IL-2 and GM-CSF in patients following HDC with BUMELTT and PBSC support. OUTLINE: PREPARATIVE REGIMEN: Patients receive busulfan orally (PO) once every 6 hours on days -8, -7, and -6; melphalan IV over 30 minutes on days -5 and -4; and thiotepa IV over 2 hours on days -3 and -2. TRANSPLANTATION: Patients undergo autologous peripheral blood stem cell infusion on day 0. POST-TRANSPLANT THERAPY: All patients receive tamoxifen citrate* PO once daily beginning prior to aldesleukin (IL-2) and sargramostim (GM-CSF) therapy and continuing for 5 years or until relapse (estrogen receptor [ER]- or progesterone receptor [PR]-positive patients) OR until completion of IL-2/GM-CSF therapy (ER-negative or PR-negative patients). Eligible patients receive IL-2 subcutaneously (SC) daily and GM-CSF SC 3 times weekly for 12 weeks beginning 30-100 days after transplantation. Patients may receive radiotherapy after completion of IL-2/GM-CSF treatment if no prior radiotherapy was given before transplantation. *Stage IV patients not receiving IL-2/GM-CSF therapy who received tamoxifen citrate as part of adjuvant therapy and subsequently failed, receive oral anastrozole once daily for 5 years or until progression instead of tamoxifen. [*For postmenopausal patients, the choice and duration of hormonal therapy given in addition to or an alternative to tamoxifen therapy will be at the physician's discretion] Patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Estrogen Receptor-negative Breast Cancer, Estrogen Receptor-positive Breast Cancer, Inflammatory Breast Cancer, Male Breast Cancer, Progesterone Receptor-negative Breast Cancer, Progesterone Receptor-positive Breast Cancer, Stage IIIB Breast Cancer, Stage IV Breast Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I
Arm Type
Experimental
Arm Description
See Detailed Description.
Intervention Type
Drug
Intervention Name(s)
tamoxifen citrate
Other Intervention Name(s)
Nolvadex, TAM, tamoxifen, TMX
Intervention Description
Given orally
Intervention Type
Drug
Intervention Name(s)
busulfan
Other Intervention Name(s)
BSF, BU, Misulfan, Mitosan, Myeloleukon
Intervention Description
Given orally
Intervention Type
Drug
Intervention Name(s)
thiotepa
Other Intervention Name(s)
Oncotiotepa, STEPA, TESPA, Tespamin, TSPA
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
melphalan
Other Intervention Name(s)
Alkeran, CB-3025, L-PAM, L-phenylalanine mustard, L-Sarcolysin
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
aldesleukin
Other Intervention Name(s)
IL-2, Proleukin, recombinant human interleukin-2, recombinant interleukin-2
Intervention Description
Given SC
Intervention Type
Biological
Intervention Name(s)
sargramostim
Other Intervention Name(s)
GM-CSF, Leukine, Prokine
Intervention Description
Given SC
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplantation
Other Intervention Name(s)
PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell
Intervention Description
Undergo autologous peripheral blood stem cell infusion
Intervention Type
Radiation
Intervention Name(s)
radiation therapy
Other Intervention Name(s)
irradiation, radiotherapy, therapy, radiation
Intervention Description
May undergo radiotherapy after completion of IL-2/GM-CSF
Primary Outcome Measure Information:
Title
Event-free Survival
Description
Event-free survival of patients treated for inflammatory (Stage IIIb) and responsive stage IV breast cancer with BUMELTT and PBSC support and low dose immunotherapy with IL2 and GM-CSF.
Time Frame
11 years
Secondary Outcome Measure Information:
Title
Overall Survival
Description
Overall survival of patients treated for inflammatory (Stage IIIb) and responsive stage IV breast cancer with BUMELTT and PBSC support and low dose immunotherapy with IL2 and GM-CSF.
Time Frame
11 years
Title
Number of Participants With Toxicity of a Combination of Low-dose IL-2 and GM-CSF
Description
IL-2/GM-CSF toxicity assessed using the NCI Toxicity Criteria. Toxicity was defined as any grade 2, 3, 4 or 5 CNS (except grade 0-3 malaise and fatigue) toxicity; any grade 3, 4, or 5 non-CNS or non-hematological toxicity (except grade 0-3 bilirubin); or any grade 4 or 5 hematological toxicity.
Time Frame
16 Weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with inflammatory (stage IIIb) or responsive stage IV breast cancer with metastasis to soft tissue and/or bone; responsive stage IV disease is defined as patients who achieve a PR (>= 50% reduction in measurable tumor burden) or CR following initial chemotherapy for metastatic disease or patients with locally recurrent disease (chest wall/axillary nodes) who are rendered disease-free following surgery or radiation therapy without receiving chemotherapy; bone disease is categorized as responsive if there is demonstrated sclerosis of prior lesions with no new lesions Patients should have received 4-7 cycles of an Adriamycin and/or taxane-based regimen for stage IIIb or stage IV disease; locally recurrent (chest wall/axillary nodes) patients rendered NED by RT or surgery do not need to receive chemotherapy for stage IV disease prior to Cytoxan/Taxol Patient has received Cytoxan 4 gm/m^2 x 1 and Taxol 250 mg/m^2 x 1 per FHCRC protocol 506.03; Cytoxan/Taxol must be given after all other chemotherapy is completed and before transplant Stem cells were collected after mobilization with Cytoxan/Taxol or after mobilization from an FHCRC approved cytokine protocol; if syngeneic collection, PBSC's were collected by using G-CSF according to FHCRC protocol 753; patient has an adequate number of peripheral blood stem cells stored (>= 2.5 x 10^6 CD34+ cells/kg) The patient must have the capacity to give informed consent; the patient must have signed an approved consent form conforming with federal and institutional guidelines Hepatic function: Bilirubin =< 2 mg%; SGOT or SGPT =< 2.5 x institutional normal Renal function: Creatinine =< 2.0 mg/dl or a creatinine clearance >= 50 mg/min Pre-Study tests have been performed as outlined in the Study Calendar Patients will begin IL-2/GM-CSF therapy if they meet the following criteria post-transplant: Can start therapy 30 to 100 days after transplant Karnofsky performance status > 60 ANC > 1,000 cells/mm^3 and platelets > 30,000/cells/mm^3 (transfusion independent) for at least 5 days before starting therapy Total bilirubin =< 2.5 x upper limit of normal SGOT =< 2.5 x upper limit of normal Creatinine =< 2.0 mg/dl Exclusion Criteria: Patients with a Karnofsky Performance Score less than 70 Patients with a left ventricular ejection fraction less than 50 % (LVEF must be performed in patients with symptoms of CHF, abnormal cardiac exam or history of Adriamycin therapy total dose > 400 mg/m^2) Patient is pregnant Patient is seropositive for the human immunodeficiency virus Patients with a history of seizures Patients with hypersensitivity to E.coli preparations Patients with active auto-immune disease Patients with clinically significant pulmonary disease, i.e., diffusion capacity corrected < 60% of predicted; patients with pulmonary problems should be evaluated with appropriate pulmonary studies and/or consult Patients with a history of CNS lesion (brain or carcinoid meningitis) Patients with significant active infection precluding transplant Patients who have had more than one prior chemotherapy regimen for stage IV disease or a prior transplant for any stage disease Patients who have had CD34+ selection of their PBSC products Patients will not receive IL-2/GM-CSF therapy if they: Are > 100 days from transplant Have documented disease progression after transplant Have an active infection Manifested cardiac complications during the initial transplant period, including arrhythmias (that required therapy), congestive heart failure, angina, myocardial infarct, or decreased LVEF to < 45% Currently have pericardial effusions, pleural effusions or ascites Manifested pulmonary toxicity during the initial transplant period and have a diffusion capacity corrected =< 60% Are on steroids Currently have a Grade 3 toxicity from BuMelTT If the patient does not wish to receive the therapy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Leona A Holmberg
Organizational Affiliation
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutchinson Cancer Research Center/Puget Sound Oncology Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Combination Chemotherapy and Peripheral Blood Stem Cell Transplant Followed By Aldesleukin and Sargramostim in Treating Patients With Inflammatory Stage IIIB or Metastatic Stage IV Breast Cancer

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