Phase I/II Study of Escalating-Dose Melphalan w/Autologous SCS & Amifostine Cytoprotect

Sponsor

University of Kentucky (Other)

Overall Status

Completed

CT.gov ID

NCT00003425

Collaborator

(none)

Enrollment

Locations

Arm

6.3

Patients Per Site

Study Details

Study Description

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 may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Chemoprotective drugs such as amifostine may protect normal cells from the side effects of chemotherapy.

PURPOSE: Phase I/II trial to study the effectiveness of high-dose melphalan plus peripheral stem cell transplantation and amifostine in treating patients with cancer.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Leukemia Lymphoma Neuroblastoma Ovarian Cancer Sarcoma Unspecified Adult Solid Tumor, Protocol Specific	Biological: filgrastim Drug: amifostine trihydrate Drug: cyclophosphamide Drug: melphalan Procedure: peripheral blood stem cell transplantation	Phase 1/Phase 2

Detailed Description

OBJECTIVES: I. Determine the maximum tolerated dose of high dose melphalan with autologous peripheral blood stem cell support and amifostine cytoprotection in patients with cancer. II. Determine the complete response rate, event free survival, overall survival, and nonrelapse mortality in this patient population.

OUTLINE: This is a dose escalation study of melphalan. Prior to high dose melphalan and amifostine cytoprotection, patients may receive cyclophosphamide IV. Filgrastim (G-CSF) is given until cytapheresis is completed. Patients receive high dose melphalan according to an escalating dose schedule. High dose melphalan is administered IV on day -1. Amifostine is also administered on days -2 and -1. Peripheral blood stem cell transplantation is performed on day 0. Dose escalation of high dose melphalan continues until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 8 patients experience dose limiting toxicity. After the MTD of high dose melphalan is determined, additional patients are treated at this dose level. Patients are followed at days 30, 100, 365, and yearly thereafter.

PROJECTED ACCRUAL: After the determination of MTD, a total of 14-25 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

25 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase I/II Study of Escalating Dose Melphalan With Autologous Pluripotent Hematopoietic Stem Cell Support and Amifostine Cytoprotection in Cancer Patients

Study Start Date :

Dec 1, 1997

Actual Primary Completion Date :

Jul 1, 2002

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Amifostine trihydrate	Biological: filgrastim Drug: amifostine trihydrate Other Names: WR-2721 Drug: cyclophosphamide Drug: melphalan Procedure: peripheral blood stem cell transplantation

Arm

Intervention/Treatment

Experimental: Amifostine trihydrate

Biological: filgrastim

Drug: amifostine trihydrate

Other Names:

WR-2721

Drug: cyclophosphamide

Drug: melphalan

Procedure: peripheral blood stem cell transplantation

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

14 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS: Confirmed diagnosis of primary tumor and/or recurrence that has a low curative potential using other therapies, including but not limited to: Acute leukemia Myeloma Breast cancer Ovarian cancer Hodgkin's disease Non-Hodgkin's lymphoma Neuroblastoma Ewing's sarcoma In the absence of recurrence, malignancies for which an autotransplant regimen is considered a reasonable therapeutic alternative are also considered Greater than 25% of bone marrow normal cellularity and less than 10% of volume composed of tumor cells No active brain metastases or carcinomatous meningitis (controlled CNS metastases eligible)

PATIENT CHARACTERISTICS: Age: 14 to 70 Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: WBC greater than 3000/mm3 Absolute neutrophil count greater than 1500/mm3 Platelet count greater than 100,000/mm3 Hepatic: Bilirubin, SGOT, and SGPT less than 2 times normal Renal: Creatinine clearance greater than 60 mL/min Cardiovascular: LVEF at least 45% Pulmonary: DLCO at least 50% FEV1 at least 60% Other: Not pregnant or nursing Fertile patients must use effective contraception HIV, HTLV-1, and HTLV-2 negative Hepatitis B and C negative

PRIOR CONCURRENT THERAPY: Biologic therapy: No more than 1 prior autologous peripheral blood stem cell transplant Chemotherapy: Cumulative anthracycline or equivalent dose no greater than 450 mg/m2 Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified Other: Recovered from prior therapy No antihypertensives during and 24 hours prior to amifostine administration

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Albert B. Chandler Medical Center, University of Kentucky	Lexington	Kentucky	United States	40536-0084
2	Marlene & Stewart Greenebaum Cancer Center, University of Maryland	Baltimore	Maryland	United States	21201
3	Kimmel Cancer Center of Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania	United States	19107-5541
4	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226