Combination Chemotherapy and Peripheral Stem Cell Transplantation Followed by Interleukin-2 and Sargramostim in Treating Patients With Inflammatory Stage IIIB or Metastatic Stage IV Breast Cancer

Condition(s) targeted: Breast Cancer

Intervention: aldesleukin (Drug); busulfan (Drug); melphalan (Drug); sargramostim (Drug); tamoxifen citrate (Drug); thiotepa (Drug); bone marrow ablation with stem cell support (Procedure); peripheral blood stem cell transplantation (Procedure); radiation therapy (Procedure)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: Fred Hutchinson Cancer Research Center

Official(s) and/or principal investigator(s):
Leona A. Holmberg, MD, PhD, Study Chair, Affiliation: Fred Hutchinson Cancer Research Center

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 may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Interleukin-2 and colony-stimulating factors such as sargramostim may help a person's immune system kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy and peripheral stem cell transplantation followed by interleukin-2 and sargramostim in treating patients who have 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 With 12 Weeks of Post-Engraftment Immunotherapy With Low-Dose IL-2 and GM-CSF

Study design: Treatment, Open Label

Detailed description: OBJECTIVES:

- Determine the event-free survival of patients treated with high-dose chemotherapy with

busulfan, melphalan, and thiotepa plus peripheral blood stem cell (PBSC) support followed by low dose immunotherapy with interleukin-2 (IL-2) and sargramostim (GM-CSF) for inflammatory stage IIIB and responsive stage IV breast cancer.

- Determine the toxic effects of this therapy in these patients.

OUTLINE: Peripheral blood stem cells (PBSC) are collected from the patient following stimulation with cyclophosphamide/paclitaxel/filgrastim (G-CSF) according to FHCRC 506 protocol or an approved FHCRC cytokine mobilization study. Patients must receive 1 course of cyclophosphamide and paclitaxel if cytokines alone are used to mobilize cells (FHCRC-506. 03 protocol). G-CSF alone will be used to collect syngeneic PBSC (FHCRC-753).

Patients receive oral busulfan every 6 hours on days - 8, -7, and -6. Melphalan IV is given on

days - 5 and -4 beginning at least 12 hours after busulfan. Thiotepa IV is given on days -3

and - 2 followed by PBSC infusion on day 0 beginning 36-48 hours after the last dose of

thiotepa.

All patients receive oral tamoxifen daily after transplant for 5 years or until relapse. Eligible patients receive interleukin-2 (IL-2) subcutaneously (SQ) daily plus sargramostim (GM-CSF) SQ on Monday, Wednesday, and Friday for 12 weeks beginning 30-100 days after transplantation. Patients with negative estrogen and progesterone status may discontinue tamoxifen therapy following IL-2/GM-CSF treatment. Patients receive radiotherapy after IL-2/GM-CSF treatment if no prior radiotherapy was given before transplantation.

Patients are followed every 3 months for 2 years, then every 6 months thereafter.

PROJECTED ACCRUAL: Approximately 70 patients will be accrued for this study over 2 years.

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

DISEASE CHARACTERISTICS:

- Stage IIIB inflammatory breast cancer

- Received 4-7 courses of doxorubicin or taxane based regimen

- Responsive stage IV breast cancer metastatic to soft tissue and/or bone

- Partial or complete response after initial chemotherapy for metastatic disease

- Received 4-7 courses of doxorubicin or taxane based regimen OR

- Locally recurrent disease rendered disease free after surgery or radiotherapy

- Bone disease responsive if demonstrated sclerosis of prior lesions with no new

lesions

- Received 1 course of cyclophosphamide 4 g/m^2 and paclitaxel 250 mg/m^2 on protocol

FHCRC-506. 03

- Stem cell collection after mobilization with cyclophosphamide/paclitaxel or after an

FHCRC approved cytokine protocol

- Syngeneic stem cells collected by using filgrastim (G-CSF) according to protocol

FHCRC-753

- Adequate number of peripheral blood stem cells stored (at least 2,500,000 CD34+

cells)

- No CNS lesion (brain or carcinoid meningitis)

- Hormone receptor status:

- Any status

PATIENT CHARACTERISTICS:

Age:

- 18 to 65

Menopausal status:

- Not specified

Performance status:

- Karnofsky 70-100%

Life expectancy:

- Not specified

Hematopoietic:

- Not specified

Hepatic:

- Bilirubin no greater than 2 mg/dL

- SGOT or SGPT no greater than 2. 5 times normal

Renal:

- Creatinine no greater than 2 mg/dL OR

- Creatinine clearance at least 50 mg/min

Cardiovascular:

- LVEF greater than 50%

- LVEF must be performed for symptoms of congestive heart failure, abnormal cardiac

exam, or history of doxorubicin total dose greater than 400 mg/m^2

Pulmonary:

- No clinically significant pulmonary disease (diffusion capacity corrected less than

60% of predicted)

Other:

- Not pregnant

- HIV negative

- No history of seizures

- No hypersensitivity to E. coli preparations

- No active autoimmune disease

- No significant active infection precluding transplantation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- No prior transplantation

Chemotherapy:

- See Disease Characteristics

- No more than 1 prior chemotherapy regimen for stage IV disease

Endocrine therapy:

- Not specified

Radiotherapy:

- Not specified

Surgery:

- Not specified

Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, United States

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: November 1997
Last updated: May 23, 2008