search
Back to results

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

Primary Purpose

Breast Cancer, Leukemia, Lymphoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
filgrastim
amifostine trihydrate
cyclophosphamide
melphalan
peripheral blood stem cell transplantation
Sponsored by
University of Kentucky
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring 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

Eligibility Criteria

14 Years - 70 Years (Child, Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Albert B. Chandler Medical Center, University of Kentucky
  • Marlene & Stewart Greenebaum Cancer Center, University of Maryland
  • Kimmel Cancer Center of Thomas Jefferson University - Philadelphia
  • Medical College of Wisconsin

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Amifostine trihydrate

Arm Description

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 1, 1999
Last Updated
April 25, 2013
Sponsor
University of Kentucky
search

1. Study Identification

Unique Protocol Identification Number
NCT00003425
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2013
Overall Recruitment Status
Completed
Study Start Date
December 1997 (undefined)
Primary Completion Date
July 2002 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Kentucky

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer, Leukemia, Lymphoma, Neuroblastoma, Ovarian Cancer, Sarcoma, Unspecified Adult Solid Tumor, Protocol Specific
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Amifostine trihydrate
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
filgrastim
Intervention Type
Drug
Intervention Name(s)
amifostine trihydrate
Other Intervention Name(s)
WR-2721
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Type
Drug
Intervention Name(s)
melphalan
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplantation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
14 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Donna E. Reece, MD
Organizational Affiliation
Lucille P. Markey Cancer Center at University of Kentucky
Official's Role
Study Chair
Facility Information:
Facility Name
Albert B. Chandler Medical Center, University of Kentucky
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536-0084
Country
United States
Facility Name
Marlene & Stewart Greenebaum Cancer Center, University of Maryland
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Kimmel Cancer Center of Thomas Jefferson University - Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107-5541
Country
United States
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
14767498
Citation
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. doi: 10.1038/sj.bmt.1704424.
Results Reference
result

Learn more about this trial

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

We'll reach out to this number within 24 hrs