Cyclophosphamide and Filgrastim Followed By SCT in Patients With Chronic or Accelerated Phase Myelogenous Leukemia

Sponsor

Masonic Cancer Center, University of Minnesota (Other)

Overall Status

Terminated

CT.gov ID

NCT00005984

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Giving colony-stimulating factors, such as G-CSF, and cyclophosphamide helps stem cells move from the patient's bone marrow to the blood so they can be collected and stored. Chemotherapy and radiation therapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy and radiation therapy.

PURPOSE: This phase II trial is studying how well cyclophosphamide plus filgrastim followed by stem cell transplant works in treating patients with chronic phase or accelerated phase chronic myelogenous leukemia.

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

Detailed Description

OBJECTIVES:

Assess the clinical outcomes, survival, and morbidity of patients with chronic or accelerated phase chronic myelogenous leukemia when treated with cyclophosphamide and filgrastim (G-CSF) followed by autologous peripheral blood stem cell transplantation.
Determine whether priming with cyclophosphamide and filgrastim (G-CSF) increases the fraction of benign Philadelphia chromosome negative hematopoietic progenitors in peripheral blood stem cells (PBSC) and reduces the incidence of persistent or recurrent leukemia after autologous transplantation with mobilized PBSC in these patients.

OUTLINE: Patients receive priming therapy consisting of cyclophosphamide IV over 2 hours on day 1 and filgrastim (G-CSF) daily subcutaneously (SQ) starting on day 5 and continuing until completion of leukapheresis. Peripheral blood stem cells (PBSC) are collected between days 14-21.

Patients then receive preparative therapy for transplant consisting of cyclophosphamide IV over 2 hours on days -7 and -6 and total body irradiation twice a day on days -4 through -1. Patients receive the PBSC transplantation on day 0. Patients also receive G-CSF IV starting on day 0 and continuing until blood counts recover. Patients then receive interferon alfa SQ daily in the absence of unacceptable toxicity or disease progression.

Patients are followed at 3 weeks; then at 3, 6, 9, 12, and 18 months; and then annually for 5 years.

PROJECTED ACCRUAL: Not specified

Study Design

Study Type:

Interventional

Actual Enrollment :

22 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Autologous Marrow Transplantation for Chronic Myelogenous Leukemia Using Stem Cells Obtained After In Vivo Cyclophosphamide/G-CSF Priming

Study Start Date :

Aug 1, 2000

Actual Primary Completion Date :

Sep 1, 2005

Actual Study Completion Date :

Sep 1, 2005

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Patients with CML Patients treated for chronic accelerated phase and/or chronic myelogenous leukemia (CML)	Drug: cyclophosphamide intravenously over 2 hours on day 1 and on days -7 and -6 Other Names: Endoxan Cytoxan Drug: filgrastim filgrastim (G-CSF) daily subcutaneously (SQ) starting on day 5 and continuing until completion of leukapheresis. Patients also receive G-CSF IV starting on day 0 and continuing until blood counts recover Other Names: NEUPOGEN® Drug: recombinant interferon alfa Beginning on Day 1, subcutaneous (SQ) daily administration in the absence of unacceptable toxicity or disease progression Other Names: INTRON® A Procedure: peripheral blood stem cell transplantation Patients receive the PBSC transplantation on day 0. Other Names: bone marrow transplant Procedure: radiation therapy total body irradiation twice a day on days -4 through -1 Other Names: irradiation

Arm

Intervention/Treatment

Experimental: Patients with CML

Patients treated for chronic accelerated phase and/or chronic myelogenous leukemia (CML)

Drug: cyclophosphamide

intravenously over 2 hours on day 1 and on days -7 and -6

Other Names:

Endoxan

Cytoxan

Drug: filgrastim

filgrastim (G-CSF) daily subcutaneously (SQ) starting on day 5 and continuing until completion of leukapheresis. Patients also receive G-CSF IV starting on day 0 and continuing until blood counts recover

Other Names:

NEUPOGEN®

Drug: recombinant interferon alfa

Beginning on Day 1, subcutaneous (SQ) daily administration in the absence of unacceptable toxicity or disease progression

Other Names:

INTRON® A

Procedure: peripheral blood stem cell transplantation

Patients receive the PBSC transplantation on day 0.

Other Names:

bone marrow transplant

Procedure: radiation therapy

total body irradiation twice a day on days -4 through -1

Other Names:

irradiation

Outcome Measures

Primary Outcome Measures

Time to hemopoietic recovery after transplantation []
Detection of the Philadelphia chromosome or the BCR/ABL gene abnormality in post-transplantation marrow samples []

Secondary Outcome Measures

Time to initial hospital discharge []
Peritransplantation toxicity []
Quality of life at various time points []
Cause of death []

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed chronic or accelerated phase chronic myelogenous leukemia (CML)
Philadelphia chromosome positive OR
BCR/ABL rearrangement
Ineligible or refused to participate in ongoing allogeneic marrow donor transplant protocols
70 and under
Performance status:
Age 65-70 years:
Karnofsky 80-100%
Under 65 years:
Karnofsky 90-100%
Renal:
Age 65-70 years:
Creatinine clearance greater than 60 mL/min (if creatinine at least 1.5 mg/dL)
Under 65 years:
Not specified
Cardiovascular:
Age 65-70 years:
LVEF at least 45%
Pulmonary:
Age 65-70 years:
If history of smoking or respiratory symptoms, spirometry and DLCO must be greater then 50% of predicted
Normal organ function (excluding bone marrow)

Exclusion Criteria:

Blast crisis or post blast crisis
Severe fibrosis defined by bilateral trephine biopsies
Splenomegaly (below umbilicus) that does not respond to chemotherapy and/or radiotherapy