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

NCT00003199 | Completed Phase 2 Results

• 2 other identifiers: PSOC 1605NCI-2010-00728
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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.

  11 years

Secondary Outcomes (2)

• Overall Survival

  11 years

• Number of Participants With Toxicity of a Combination of Low-dose IL-2 and GM-CSF

  16 Weeks

Study Arms (1)

Arm I

EXPERIMENTAL

See Detailed Description.

Drug: tamoxifen citrate; Drug: busulfan; Drug: thiotepa; Drug: melphalan; Biological: aldesleukin; Biological: sargramostim; Procedure: peripheral blood stem cell transplantation; Radiation: radiation therapy

Interventions

tamoxifen citrate DRUG

Given orally

Also known as: Nolvadex, TAM, tamoxifen, TMX

Arm I

busulfan DRUG

Given orally

Also known as: BSF, BU, Misulfan, Mitosan, Myeloleukon

Arm I

thiotepa DRUG

Given IV

Also known as: Oncotiotepa, STEPA, TESPA, Tespamin, TSPA

Arm I

melphalan DRUG

Given IV

Also known as: Alkeran, CB-3025, L-PAM, L-phenylalanine mustard, L-Sarcolysin

Arm I

aldesleukin BIOLOGICAL

Given SC

Also known as: IL-2, Proleukin, recombinant human interleukin-2, recombinant interleukin-2

Arm I

sargramostim BIOLOGICAL

Given SC

Also known as: GM-CSF, Leukine, Prokine

Arm I

peripheral blood stem cell transplantation PROCEDURE

Undergo autologous peripheral blood stem cell infusion

Also known as: PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell

Arm I

radiation therapy RADIATION

May undergo radiotherapy after completion of IL-2/GM-CSF

Also known as: irradiation, radiotherapy, therapy, radiation

Arm I

Eligibility Criteria

• Age: 19 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutchinson Cancer Research Center/Puget Sound Oncology Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Inflammatory Breast Neoplasms; Breast Neoplasms, Male; Breast Neoplasms

Interventions

Tamoxifen; Busulfan; Thiotepa; Melphalan; aldesleukin; Interleukin-2; sargramostim; Granulocyte-Macrophage Colony-Stimulating Factor; Peripheral Blood Stem Cell Transplantation; Radiotherapy; Radiation

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramides; Organophosphorus Compounds; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Lymphokines; Proteins; Biological Factors; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Physical Phenomena

Results Point of Contact

• Title: Dr. Leona A. Holmberg
• Organization: Fred Hutchinson Cancer Research Center

lholmber@fredhutch.org

206-667-6447

Study Officials

• Leona A Holmberg

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 1, 1999
• First Posted: January 27, 2003
• Study Start: November 1, 1997
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: July 12, 2017
• Results First Posted: May 17, 2017

Record last verified: 2017-06

Locations

US (1)