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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Kentucky
ClinicalTrials.gov Identifier:
NCT00003425
First received: November 1, 1999
Last updated: April 25, 2013
Last verified: April 2013
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University of Kentucky:

Estimated Enrollment: 25
Study Start Date: December 1997
Primary Completion Date: July 2002 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Amifostine trihydrate Biological: filgrastim Drug: amifostine trihydrate
Other Name: WR-2721
Drug: cyclophosphamide Drug: melphalan Procedure: peripheral blood stem cell transplantation

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.

  Eligibility

Ages Eligible for Study:   14 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003425

Locations
United States, Kentucky
Albert B. Chandler Medical Center, University of Kentucky
Lexington, Kentucky, United States, 40536-0084
United States, Maryland
Marlene & Stewart Greenebaum Cancer Center, University of Maryland
Baltimore, Maryland, United States, 21201
United States, Pennsylvania
Kimmel Cancer Center of Thomas Jefferson University - Philadelphia
Philadelphia, Pennsylvania, United States, 19107-5541
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
University of Kentucky
Investigators
Study Chair: Donna E. Reece, MD Lucille P. Markey Cancer Center at University of Kentucky
  More Information

Additional Information:
Publications:
Responsible Party: University of Kentucky
ClinicalTrials.gov Identifier: NCT00003425     History of Changes
Other Study ID Numbers: UKMC-97BMT72, CDR0000066448, ALZA-UKMC-97BMT72, NCI-V98-1455
Study First Received: November 1, 1999
Last Updated: April 25, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of Kentucky:
stage III adult Hodgkin lymphoma
stage IV adult Hodgkin lymphoma
stage IV breast cancer
stage IIIA breast cancer
recurrent breast cancer
stage IIIB breast cancer
recurrent adult Hodgkin lymphoma
refractory multiple myeloma
stage III ovarian epithelial cancer
stage IV ovarian epithelial cancer
recurrent ovarian epithelial cancer
regional neuroblastoma
disseminated neuroblastoma
stage 4S neuroblastoma
recurrent neuroblastoma
stage III multiple myeloma
recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
unspecified adult solid tumor, protocol specific
untreated adult acute lymphoblastic leukemia
untreated adult acute myeloid leukemia
adult acute myeloid leukemia in remission
adult acute lymphoblastic leukemia in remission
ovarian stromal cancer
stage III ovarian germ cell tumor
stage IV ovarian germ cell tumor
recurrent ovarian germ cell tumor
acute undifferentiated leukemia
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma

Additional relevant MeSH terms:
Breast Neoplasms
Leukemia
Lymphoma
Neuroblastoma
Ovarian Neoplasms
Sarcoma
Adnexal Diseases
Breast Diseases
Endocrine Gland Neoplasms
Endocrine System Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Connective and Soft Tissue
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Neuroectodermal Tumors, Primitive, Peripheral
Ovarian Diseases
Skin Diseases

ClinicalTrials.gov processed this record on October 23, 2014