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

Phase 2

Terminated

• Conditions: Leukemia
• Interventions: Drug: cyclophosphamide; Drug: filgrastim; Drug: recombinant interferon alfa; Procedure: peripheral blood stem cell transplantation; Procedure: radiation therapy

• Registration Number: NCT00005984
• Lead Sponsor: Masonic Cancer Center, University of Minnesota

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.

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 Timeline

• Study First Submitted: 2000-07-05
• Study Start: 2000-08
• Study First Submitted QC: 2003-01-26
• Study First Posted: 2003-01-27
• Primary Completion: 2005-09
• Study Completion: 2005-09
• Status Verified: 2017-09
• Last Update Submitted: 2017-11-27
• Last Update Posted: 2017-11-29

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 22

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Patients with CML	recombinant interferon alfa	Patients treated for chronic accelerated phase and/or chronic myelogenous leukemia (CML)
Patients with CML	peripheral blood stem cell transplantation	Patients treated for chronic accelerated phase and/or chronic myelogenous leukemia (CML)
Patients with CML	radiation therapy	Patients treated for chronic accelerated phase and/or chronic myelogenous leukemia (CML)
Patients with CML	filgrastim	Patients treated for chronic accelerated phase and/or chronic myelogenous leukemia (CML)
Patients with CML	cyclophosphamide	Patients treated for chronic accelerated phase and/or chronic myelogenous leukemia (CML)

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

University of Minnesota Cancer Center; 🇺🇸 Minneapolis, Minnesota, United States