Phase I/II Study of Escalating Dose Melphalan With Autologous Pluripotent Hematopoietic Stem Cell Support and Amifostine Cytoprotection in Cancer Patients
14 Years
70 Years
Both
Breast Cancer, Leukemia, Lymphoma, Neuroblastoma, Ovarian Cancer, Sarcoma, Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
Phase I/II Study of Escalating Dose Melphalan With Autologous Pluripotent Hematopoietic Stem Cell Support and Amifostine Cytoprotection in Cancer Patients
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Principal Investigator
Donna E. Reece, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Lucille P. Markey Cancer Center at University of Kentucky
Authority:
United States: Food and Drug Administration
Study ID:
UKMC-97BMT72
NCT ID:
NCT00003425
Start Date:
December 1997
Completion Date:
Related Keywords:
- Breast Cancer
- Leukemia
- Lymphoma
- Neuroblastoma
- Ovarian Cancer
- Sarcoma
- Unspecified Adult Solid Tumor, Protocol Specific
- 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
- stage III grade 3 follicular lymphoma
- stage III adult diffuse small cleaved cell lymphoma
- stage III adult diffuse mixed cell lymphoma
- stage III adult diffuse large cell lymphoma
- stage III adult immunoblastic large cell lymphoma
- stage III adult lymphoblastic lymphoma
- stage III adult Burkitt lymphoma
- stage IV grade 1 follicular lymphoma
- stage IV grade 2 follicular lymphoma
- stage IV grade 3 follicular lymphoma
- stage IV adult diffuse small cleaved cell lymphoma
- stage IV adult diffuse mixed cell lymphoma
- stage IV adult diffuse large cell lymphoma
- stage IV adult immunoblastic large cell lymphoma
- stage IV adult lymphoblastic lymphoma
- stage IV adult Burkitt lymphoma
- recurrent grade 1 follicular lymphoma
- recurrent grade 2 follicular lymphoma
- recurrent grade 3 follicular lymphoma
- recurrent adult diffuse small cleaved cell lymphoma
- recurrent adult diffuse mixed cell lymphoma
- recurrent adult diffuse large cell lymphoma
- recurrent adult immunoblastic large cell lymphoma
- recurrent adult lymphoblastic lymphoma
- recurrent adult Burkitt lymphoma
- secondary acute myeloid leukemia
- borderline ovarian surface epithelial-stromal tumor
- ovarian sarcoma
- localized unresectable neuroblastoma
- stage III mantle cell lymphoma
- stage IV mantle cell lymphoma
- recurrent mantle cell lymphoma
- metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor
- recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor
- recurrent marginal zone lymphoma
- recurrent small lymphocytic lymphoma
- stage III small lymphocytic lymphoma
- stage III marginal zone lymphoma
- stage IV small lymphocytic lymphoma
- stage IV marginal zone lymphoma
- extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
- nodal marginal zone B-cell lymphoma
- splenic marginal zone lymphoma
- Breast Neoplasms
- Leukemia
- Lymphoma
- Lymphoma, Non-Hodgkin
- Neuroblastoma
- Ovarian Neoplasms
- Lymphoma, Large-Cell, Immunoblastic
- Neuroectodermal Tumors, Primitive, Peripheral
- Sarcoma
Name | Location |
|---|---|
| Albert B. Chandler Medical Center, University of Kentucky | Lexington, Kentucky 40536-0084 |
| Kimmel Cancer Center of Thomas Jefferson University - Philadelphia | Philadelphia, Pennsylvania 19107 |
| Marlene & Stewart Greenebaum Cancer Center, University of Maryland | Baltimore, Maryland 21201 |
| Medical College of Wisconsin | Milwaukee, Wisconsin 53226 |
