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Chemotherapy Followed by Peripheral Stem Cell Transplantation in Treating Patients With Myelofibrosis

Primary Purpose

Chronic Myeloproliferative Disorders

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
filgrastim
busulfan
cytarabine
idarubicin
peripheral blood stem cell transplantation
Sponsored by
Fred Hutchinson Cancer Center
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Myeloproliferative Disorders focused on measuring polycythemia vera, chronic idiopathic myelofibrosis, essential thrombocythemia

Eligibility Criteria

undefined - 75 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Diagnosis of idiopathic myelofibrosis or other myeloproliferative disorder with myelofibrosis Evidence of advanced disease or hematologic abnormalities due to severe fibrosis such as 1 or more of the following poor prognostic factors: Hemoglobin less than 10 g/dL Platelet count less than 100,000/mm3 WBC less than 4,000/mm3 Symptomatic splenomegaly Constitutional symptoms inadequately controlled with low dose chemotherapy Abnormal karyotype Patients without evidence of advanced disease undergo PBSC harvest and transplantation is delayed until there is evidence of disease progression Leukemia progression (greater than 15% peripheral blood blasts) allowed if the history of a chronic myeloproliferative disorder of at least 6 months duration is well documented Ineligible for or refusal of allogeneic transplantation No other cause of myelofibrosis other than myeloproliferative disorders, such as the following: Metastatic carcinoma Lymphoma Hairy cell leukemia Myelodysplastic syndrome De novo acute leukemia Collagen vascular disorders Granulomatous infections PATIENT CHARACTERISTICS: Age: 75 and under Performance status: Not specified Life expectancy: Not specified Hematopoietic: See Disease Characteristics WBC no greater than 30,000/mm3 (may be reduced to less than 30,000/mm3 using hydroxyurea or induction chemotherapy) Hepatic: Bilirubin no greater than 2 times upper limit of normal (ULN)* Transaminases no greater than 2 times ULN* * Unless due to extramedullary hematopoiesis in the liver Renal: Creatinine no greater than 2 times normal OR Creatinine clearance at least 50% Cardiovascular: No prior or active congestive heart failure* LVEF at least 50%* *If receiving study cytoreductive therapy Pulmonary: Total lung capacity at least 50% predicted OR Corrected DLCO at least 50% predicted Other: No active infection No poorly controlled seizure disorders Not pregnant or nursing Negative pregnancy test Fertile patients must use effective barrier contraception HIV negative PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics Chemotherapy: See Disease Characteristics At least 7 days since prior hydroxyurea Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified

Sites / Locations

  • Katmai Oncology Group
  • H. Lee Moffitt Cancer Center and Research Institute
  • University of Illinois College of Medicine
  • Mayo Clinic Cancer Center
  • Washington University Siteman Cancer Center
  • New York Presbyterian Hospital - Cornell Campus
  • Fred Hutchinson Cancer Research Center
  • Hopital Saint-Louis
  • Addenbrooke's NHS Trust

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
October 4, 2000
Last Updated
June 15, 2010
Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00006367
Brief Title
Chemotherapy Followed by Peripheral Stem Cell Transplantation in Treating Patients With Myelofibrosis
Official Title
Autologous Peripheral Blood Stem Cell Mobilization and Transplantation for Myelofibrosis
Study Type
Interventional

2. Study Status

Record Verification Date
June 2010
Overall Recruitment Status
Completed
Study Start Date
May 2000 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
January 2004 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

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 cancer cells. PURPOSE: Phase II trial to study the effectiveness of chemotherapy followed by peripheral stem cell transplantation in treating patients who have myelofibrosis.
Detailed Description
OBJECTIVES: I. Determine the ability of myeloablative chemotherapy followed by peripheral blood stem cell (PBSC) transplantation to restore effective marrow hematopoieses in patients with advanced idiopathic myelofibrosis or myelofibrosis secondary to other myeloproliferative disorders. II. Determine the ability of this regimen to palliate symptoms and prolong survival in these patients. III. Determine if there is evidence of clonal hematopoieses before PBSC mobilization, in the PBSC product, and after transplantation in these patients. IV. Correlate the properties of the peripheral blood before mobilization and the PBSC product with engraftment in these patients. V. Correlate the markers of angiogenesis with clinical parameters in these patients. OUTLINE: Patients with evidence of leukemic progression receive cytoreduction therapy consisting of idarubicin IV on days 1-3 and cytarabine IV continuously over days 1-7 followed by filgrastim (G-CSF) subcutaneously (SC) daily until blood counts recover and leukapheresis is completed. Patients undergo leukapheresis beginning when blood counts recover and continuing until the target number of cells are collected. Patients with no evidence of leukemic progression receive filgrastim SC daily until leukapheresis is completed. Patients undergo leukapheresis beginning on day 4 and continuing until the target number of cells are collected. Patients receive myeloablative therapy consisting of oral busulfan every six hours on days -5 to -2. Patients with leukemic progression begin myeloablative therapy at least 28 days after completion of chemotherapy. Patients receive autologous peripheral blood stem cells IV on day 0. Patients are followed at 1 month, 3 months, 1 year, and then annually thereafter. PROJECTED ACCRUAL: A total of 10-44 patients will be accrued for this study within 2 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Myeloproliferative Disorders
Keywords
polycythemia vera, chronic idiopathic myelofibrosis, essential thrombocythemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
filgrastim
Intervention Type
Drug
Intervention Name(s)
busulfan
Intervention Type
Drug
Intervention Name(s)
cytarabine
Intervention Type
Drug
Intervention Name(s)
idarubicin
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplantation

10. Eligibility

Sex
All
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Diagnosis of idiopathic myelofibrosis or other myeloproliferative disorder with myelofibrosis Evidence of advanced disease or hematologic abnormalities due to severe fibrosis such as 1 or more of the following poor prognostic factors: Hemoglobin less than 10 g/dL Platelet count less than 100,000/mm3 WBC less than 4,000/mm3 Symptomatic splenomegaly Constitutional symptoms inadequately controlled with low dose chemotherapy Abnormal karyotype Patients without evidence of advanced disease undergo PBSC harvest and transplantation is delayed until there is evidence of disease progression Leukemia progression (greater than 15% peripheral blood blasts) allowed if the history of a chronic myeloproliferative disorder of at least 6 months duration is well documented Ineligible for or refusal of allogeneic transplantation No other cause of myelofibrosis other than myeloproliferative disorders, such as the following: Metastatic carcinoma Lymphoma Hairy cell leukemia Myelodysplastic syndrome De novo acute leukemia Collagen vascular disorders Granulomatous infections PATIENT CHARACTERISTICS: Age: 75 and under Performance status: Not specified Life expectancy: Not specified Hematopoietic: See Disease Characteristics WBC no greater than 30,000/mm3 (may be reduced to less than 30,000/mm3 using hydroxyurea or induction chemotherapy) Hepatic: Bilirubin no greater than 2 times upper limit of normal (ULN)* Transaminases no greater than 2 times ULN* * Unless due to extramedullary hematopoiesis in the liver Renal: Creatinine no greater than 2 times normal OR Creatinine clearance at least 50% Cardiovascular: No prior or active congestive heart failure* LVEF at least 50%* *If receiving study cytoreductive therapy Pulmonary: Total lung capacity at least 50% predicted OR Corrected DLCO at least 50% predicted Other: No active infection No poorly controlled seizure disorders Not pregnant or nursing Negative pregnancy test Fertile patients must use effective barrier contraception HIV negative PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics Chemotherapy: See Disease Characteristics At least 7 days since prior hydroxyurea Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeanne E. Anderson, MD
Organizational Affiliation
Fred Hutchinson Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Katmai Oncology Group
City
Anchorage
State/Province
Alaska
ZIP/Postal Code
99508-4627
Country
United States
Facility Name
H. Lee Moffitt Cancer Center and Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612-9497
Country
United States
Facility Name
University of Illinois College of Medicine
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Mayo Clinic Cancer Center
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Washington University Siteman Cancer Center
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
New York Presbyterian Hospital - Cornell Campus
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Fred Hutchinson Cancer Research Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109-1024
Country
United States
Facility Name
Hopital Saint-Louis
City
Paris
ZIP/Postal Code
75475
Country
France
Facility Name
Addenbrooke's NHS Trust
City
Cambridge
State/Province
England
ZIP/Postal Code
CB2 2QQ
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
11468154
Citation
Anderson JE, Tefferi A, Craig F, Holmberg L, Chauncey T, Appelbaum FR, Guardiola P, Callander N, Freytes C, Gazitt Y, Razvillas B, Deeg HJ. Myeloablation and autologous peripheral blood stem cell rescue results in hematologic and clinical responses in patients with myeloid metaplasia with myelofibrosis. Blood. 2001 Aug 1;98(3):586-93. doi: 10.1182/blood.v98.3.586.
Results Reference
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Chemotherapy Followed by Peripheral Stem Cell Transplantation in Treating Patients With Myelofibrosis

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