Chemotherapy, Filgrastim and Peripheral Stem Cell Transplantation in Patients With Chronic Myelogenous Leukemia

Sponsor

Masonic Cancer Center, University of Minnesota (Other)

Overall Status

Terminated

CT.gov ID

NCT00005986

Collaborator

(none)

Location

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer 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. Colony-stimulating factors such as filgrastim may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy.

PURPOSE: Phase II trial to study the effectiveness of chemotherapy and filgrastim followed by peripheral stem cell transplantation in treating patients who have chronic myelogenous leukemia.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Drug: busulfan Drug: cyclophosphamide Drug: filgrastim Drug: recombinant interferon alfa Procedure: in vitro-treated peripheral blood stem cell transplantation Procedure: peripheral blood stem cell transplantation Procedure: radiation therapy	Phase 2

Detailed Description

OBJECTIVES:

Assess clinical outcomes, survival, and morbidity of transplantation therapy in patients with chronic myelogenous leukemia when treated with high dose chemotherapy and filgrastim (G-CSF) followed by autologous retrovirally transduced peripheral blood stem cell (PBSC) transplantation.
Determine whether this priming treatment can increase the fraction of benign Philadelphia chromosome (Ph) negative hematopoietic progenitors in PBSC and reduce the incidence of persistent or recurrent leukemia after autologous transplantation with mobilized PBSC in these patients.
Assess whether retroviral transduction of mobilized PBSC progenitors determines the contribution of malignant Ph positive progenitors contaminating the graft to relapse after transplantation in these patients.
Determine whether this priming treatment can expand the benign progenitor population in the PBSC collections from these patients.

OUTLINE: In the priming phase, patients receive cyclophosphamide IV over 2 hours on day 1 and filgrastim (G-CSF) subcutaneously (SQ) daily beginning on day 4 and continuing until the completion of leukapheresis. Peripheral blood stem cells (PBSC) are harvested 4-7 times between days 10 and 21 beginning when blood counts recover (CD34+ cells are selected from 2 of these PBSC collections and transduced with the LN NEO virus prior to cryopreservation).

In the transplant phase, patients who have not received prior radiotherapy receive cyclophosphamide IV over 2 hours daily on days -7 and -6 and total body irradiation on days -4 through -1. Autologous PBSC and LN NEO transduced CD34+ cells are reinfused on day 0. Patients also receive G-CSF IV daily beginning on day 0 and continuing until blood counts recover.

Patients who have received prior radiotherapy receive oral busulfan every 6 hours on days -10 through -7 and cyclophosphamide IV daily on days -6 through -3. Autologous PBSC and LN NEO transduced CD34+ cells are reinfused on day 0. Patients also receive G-CSF IV daily beginning on day 0 and continuing until blood counts recover.

All patients then receive interferon alfa SQ daily until disease progression or unacceptable toxicity.

Patients are followed at 3 weeks; at 3, 6, 9, 12, 18, and 24 months; and then annually thereafter.

PROJECTED ACCRUAL: A total of 4-26 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

Autologous Transplantation for Chronic Myelogenous Leukemia Using Retrovirally Marked Peripheral Blood Progenitor Cells Obtained After In Vivo Cyclophosphamide/G-CSF Priming

Study Start Date :

Aug 1, 2000

Actual Primary Completion Date :

Sep 1, 2004

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed chronic or accelerated phase chronic myelogenous leukemia
Philadelphia chromosome positive OR
BCR/ABL rearrangement
No blast crisis or post blast crisis
No moderate to severe fibrosis defined by bilateral trephine biopsies
Not eligible for or refused to participate in allogeneic marrow transplant protocols
No splenomegaly (below umbilicus) that does not respond to chemotherapy and/or radiotherapy