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Fludarabine and Radiation Therapy in Treating Patients Who Are Undergoing Donor Stem Cell Transplant for Chronic Phase or Accelerated Phase Chronic Myelogenous Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00110058
Recruitment Status : Completed
First Posted : May 4, 2005
Last Update Posted : November 17, 2011
National Cancer Institute (NCI)
Information provided by:
Fred Hutchinson Cancer Research Center

Brief Summary:

RATIONALE: Giving low doses of chemotherapy, such as fludarabine, and radiation therapy before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) or interferon alfa after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving fludarabine together with radiation therapy works in treating patients who are undergoing donor stem cell transplant for chronic phase or accelerated phase chronic myelogenous leukemia.

Condition or disease Intervention/treatment Phase
Leukemia Biological: recombinant interferon alfa Biological: therapeutic allogeneic lymphocytes Drug: cyclosporine Drug: fludarabine phosphate Drug: imatinib mesylate Drug: mycophenolate mofetil Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy Phase 2

Detailed Description:



  • Determine the disease-free survival rate in patients with chronic or accelerated phase chronic myelogenous leukemia that failed or inadequately responded to prior imatinib mesylate treated with nonmyeloablative conditioning comprising fludarabine and low-dose total-body irradiation followed by allogeneic peripheral blood stem cell transplantation.


  • Determine the complete cytogenetic and molecular response rates in patients treated with this regimen.
  • Determine overall survival of patients treated with this regimen.
  • Determine non-relapse mortality in patients treated with this regimen.
  • Determine the incidence of serious infection, graft-versus-host disease, and myelosuppression in patients treated with this regimen.

OUTLINE: This is a multicenter study.

  • Conditioning treatment: Patients receive fludarabine IV on days -4 to -2. Patients undergo low-dose total-body irradiation (TBI) on day 0.
  • Allogeneic peripheral blood stem cell transplantation: After TBI, patients undergo allogeneic peripheral blood stem cell transplantation on day 0.
  • Immunosuppression: Patients receive oral cyclosporine twice daily on days -3 to 56 followed by a taper to day 180 in the absence of graft-versus-host disease (GVHD). Patients also receive oral mycophenolate mofetil twice daily on days 0-27.
  • Post-transplant treatment: Patients experiencing disease persistence or progression AND low donor chimerism discontinue immunosuppression. Patients with disease persistence or progression after discontinuing immunosuppression receive oral imatinib mesylate once daily. Patients who have disease improvement after day 28 of imatinib mesylate treatment AND who have no evidence of disease after day 84 of imatinib mesylate treatment continue imatinib mesylate in the absence of disease progression or unacceptable toxicity. Patients who fail to improve after day 28 of imatinib mesylate treatment OR who have residual disease after day 84 of imatinib mesylate treatment receive donor lymphocytes IV over 15-30 minutes once every 1-4 months for up to 4 infusions. Patients ineligible to receive donor lymphocytes (e.g., patients with evidence of GVHD) receive interferon alfa subcutaneously 3 times a week for up to 12 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 6, 9, 12, 18, and 24 months, and then annually for 5 years.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multi-Center Phase II Study of Nonmyeloablative Conditioning With TBI and Fludarabine for HLA-Matched Related Hematopoietic Cell Transplantation for Treatment of Chronic Myeloid Leukemia in Chronic and Accelerated Phase
Study Start Date : February 2005
Actual Study Completion Date : July 2006

Primary Outcome Measures :
  1. Progression-free survival

Secondary Outcome Measures :
  1. Rate of complete molecular response
  2. Late nonrelapse mortality
  3. Incidence and severity of graft-vs-host disease (GVHD)
  4. Incidence of serious infections
  5. Myelosuppression
  6. Overall survival and disease-free survival

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Diagnosis of Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia, meeting 1 of the following criteria:

    • Chronic phase

      • Ph+ by cytogenetics or fluorescent in situ hybridization (FISH) assay
    • Accelerated phase, meeting any of the following criteria:

      • More than 10% but < 30% myeloblasts and promyelocytes in marrow or peripheral blood
      • Any additional clonal cytogenetic abnormalities
      • Increasing splenomegaly
      • Extramedullary tumor
      • WBC, platelet count, or hematocrit perturbations not controlled by therapy with hydroxyurea, interferon, or imatinib mesylate
      • Persistent unexplained fever or bone pain
  • Less than 5% blasts in the marrow at time of transplantation
  • Not eligible for OR refused conventional myeloablative allogeneic stem cell transplantation
  • Failed OR suboptimal response to prior imatinib mesylate, as defined by 1 of the following:

    • Absence of complete hematologic response after > 3 months of treatment with imatinib mesylate
    • Absence of cytogenetic response, as defined by 1 of the following:

      • Absence of any cytogenetic response (< 95% Ph+ or BCR/ABL+ cells by cytogenetic or FISH analysis, respectively) after 6 months of treatment with imatinib mesylate
      • Absence of major cytogenetic response (< 35% Ph+ or BCR/ABL+ cells by cytogenetic or FISH analysis, respectively) after 1 year of treatment with imatinib mesylate
      • Absence of complete cytogenetic response (no Ph+ cells by cytogenetic analysis OR BCR/ABL+ cells within normal limits by FISH analysis) after 18 months of treatment with imatinib mesylate
    • Hematologic evidence of disease progression
    • Cytogenetic evidence of disease progression

      • Increase in Ph+ cells or BCR/ABL+ cells by > 20% with at least 1 month between sequential testing
    • Molecular evidence of disease progression

      • More than 10-fold increase in BCR/ABL mRNA levels by quantitative polymerase chain reaction (Q-PCR) with at least 1 month between 2 sequential tests
    • Experienced adverse events during treatment with imatinib mesylate that precluded further administration of the drug
  • No CNS disease refractory to intrathecal chemotherapy
  • HLA identical related donor available

    • Phenotypically matched at HLA-A, -B, -C, DRQ1, and DBQ1
  • No presence of circulating leukemic blasts by standard pathology



  • Any age

Performance status

  • Karnofsky 70-100% OR
  • Lansky 70-100%

Life expectancy

  • Not specified


  • See Disease Characteristics


  • No fulminant liver failure
  • No cirrhosis of the liver with evidence of portal hypertension or bridging fibrosis
  • No alcoholic hepatitis
  • No esophageal varices
  • No history of bleeding esophageal varices
  • No hepatic encephalopathy
  • No uncorrectable hepatic synthetic dysfunction evidenced by prolongation of PT
  • No ascites related to portal hypertension
  • No bacterial or fungal liver abscess
  • No biliary obstruction
  • No chronic viral hepatitis AND bilirubin > 3 mg/dL
  • No symptomatic biliary disease


  • Renal failure allowed


  • No symptomatic coronary artery disease
  • Ejection fraction ≥ 35%
  • No other cardiac failure requiring therapy
  • No poorly controlled hypertension (blood pressure ≥ 150/90 mm Hg) on standard medication


  • DLCO ≥ 30%
  • Total lung capacity ≥ 30%
  • FEV_1 ≥ 30%
  • No requirement for continuous supplementary oxygen
  • No fungal pneumonia with radiological progression after treatment with amphotericin or mold-active azoles for > 1 month


  • Not pregnant or nursing
  • Fertile patients must use effective barrier contraception during and for 12 months after completion of study treatment
  • HIV negative
  • No other disease that severely limits life expectancy
  • No other active malignancy except localized nonmelanoma skin cancer
  • No nonhematologic malignancy within the past 5 years that is currently in complete remission and has a > 20% risk of disease recurrence except for nonmelanoma skin cancer
  • No systemic uncontrolled infection
  • No active bacterial or fungal infection unresponsive to medical therapy


Biologic therapy

  • See Disease Characteristics


  • See Disease Characteristics

Endocrine therapy

  • Not specified


  • Not specified


  • Not specified


  • At least 48 hours since prior imatinib mesylate

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00110058

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United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109-1023
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109-1024
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
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Principal Investigator: Brenda Sandmaier, MD Fred Hutchinson Cancer Research Center

Layout table for additonal information Identifier: NCT00110058     History of Changes
Other Study ID Numbers: 1954.00
CDR0000423314 ( Registry Identifier: PDQ )
First Posted: May 4, 2005    Key Record Dates
Last Update Posted: November 17, 2011
Last Verified: November 2011
Keywords provided by Fred Hutchinson Cancer Research Center:
accelerated phase chronic myelogenous leukemia
childhood chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
Philadelphia chromosome positive chronic myelogenous leukemia
relapsing chronic myelogenous leukemia
Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Accelerated Phase
Neoplasms by Histologic Type
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Mycophenolic Acid
Fludarabine phosphate
Imatinib Mesylate
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Enzyme Inhibitors
Antifungal Agents
Dermatologic Agents