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

• ClinicalTrials.gov Identifier: NCT00003425
• Recruitment Status: Completed
• First Posted: February 20, 2004
• Last Update Posted: April 26, 2013
• Sponsor: University of Kentucky
• Information provided by (Responsible Party): University of Kentucky

Tracking Information

• First Submitted Date: November 1, 1999
• First Posted Date: February 20, 2004
• Last Update Posted Date: April 26, 2013
• Study Start Date: December 1997
• Actual Primary Completion Date: July 2002 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures: Not Provided
• Original Primary Outcome Measures: Not Provided
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase I/II Study of Escalating-Dose Melphalan w/Autologous SCS & Amifostine Cytoprotect
• Official Title: Phase I/II Study of Escalating Dose Melphalan With Autologous Pluripotent Hematopoietic Stem Cell Support and Amifostine Cytoprotection in Cancer Patients

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.

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 Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Breast Cancer
• Leukemia
• Lymphoma
• Neuroblastoma
• Ovarian Cancer
• Sarcoma
• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

• Biological: filgrastim
• Drug: amifostine trihydrate
  Other Name: WR-2721
• Drug: cyclophosphamide
• Drug: melphalan
• Procedure: peripheral blood stem cell transplantation

Study Arms

Experimental: Amifostine trihydrate

Interventions:

• Biological: filgrastim
• Drug: amifostine trihydrate
• Drug: cyclophosphamide
• Drug: melphalan
• Procedure: peripheral blood stem cell transplantation

• Publications *: Phillips GL, Meisenberg BR, Reece DE, Adams VR, Badros AZ, Brunner JL, Fenton RG, Filicko J, Grosso DL, Hale GA, Howard DS, Johnson VP, Kniska A, Marshall KW, Mookerjee B, Nath R, Rapoport AP, Sarkodee-Adoo C, Takebe N, Vesole DH, Wagner JL, Flomenberg N. Activity of single-agent melphalan 220-300 mg/m2 with amifostine cytoprotection and autologous hematopoietic stem cell support in non-Hodgkin and Hodgkin lymphoma. Bone Marrow Transplant. 2004 Apr;33(8):781-7.

Recruitment Information

• Recruitment Status: Completed
• Estimated Enrollment (submitted: April 9, 2007): 25
• Original Enrollment: Not Provided
• Study Completion Date: Not Provided
• Actual Primary Completion Date: July 2002 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 14 Years to 70 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00003425
• Other Study ID Numbers: UKMC-97BMT72; CDR0000066448 ( Registry Identifier: PDQ (Physician Data Query) ); ALZA-UKMC-97BMT72; NCI-V98-1455
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: University of Kentucky
• Study Sponsor: University of Kentucky
• Collaborators: Not Provided

Investigators

• Study Chair: Donna E. Reece, MD; Lucille P. Markey Cancer Center at University of Kentucky

• PRS Account: University of Kentucky
• Verification Date: April 2013