Fludarabine, Cyclophosphamide, and Total-Body Irradiation in Treating Patients Who Are Undergoing a Donor Bone Marrow Transplant for Hematologic Cancer

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
First received: August 22, 2005
Last updated: June 16, 2014
Last verified: June 2014

August 22, 2005
June 16, 2014
October 2004
December 2015   (final data collection date for primary outcome measure)
  • Transplant-related mortality at 60 days, 6 months, 1 and 2 years [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Relapse at 60 days, 6 months, 1 and 2 years [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Progression-free survival at 60 days, 6 months, 1 and 2 years [ Time Frame: 2 years ] [ Designated as safety issue: No ]
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Complete list of historical versions of study NCT00134004 on ClinicalTrials.gov Archive Site
  • Peripheral blood donor chimerism as measured by polymerase chain reaction (PCR) of variable nucleotide tandem repeats at 30 days, 60 days, and 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Hematologic and non-hematologic toxicities as measured by NCI Common Toxicity Criteria for Adverse Events, v 3.0 weekly until day 60 after transplantation [ Time Frame: 60 days ] [ Designated as safety issue: Yes ]
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Fludarabine, Cyclophosphamide, and Total-Body Irradiation in Treating Patients Who Are Undergoing a Donor Bone Marrow Transplant for Hematologic Cancer
A Phase II Trial of Non-Myeloablative Conditioning and Transplantation of Partially HLA-Mismatched Bone Marrow for Patients With Hematologic Malignancies

RATIONALE: Giving low doses of chemotherapy, such as fludarabine and cyclophosphamide, and radiation therapy before a donor bone marrow transplant helps stop the growth of cancer cells. Giving chemotherapy or radiation therapy before or after transplant also stops the patient's immune system from rejecting the donor's bone marrow stem cells. The donated stem cells may replace the patient's immune system cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus and mycophenolate mofetil after the transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving fludarabine and cyclophosphamide together with total-body irradiation works in treating patients who are undergoing a donor bone marrow transplant for hematologic cancer.


  • Determine transplant-related mortality, risk of relapse, and progression-free survival of patients with standard- or high-risk hematologic malignancies undergoing nonmyeloablative conditioning comprising fludarabine, cyclophosphamide, and total-body irradiation followed by HLA-haploidentical allogeneic bone marrow transplantation.
  • Determine donor hematopoietic chimerism in patients' peripheral blood at 30, 60, and 180 days after transplantation.
  • Determine hematologic and nonhematologic toxic effects of this regimen in these patients.
  • Determine, when feasible, surface expression of HLA molecules and death receptors, sensitivity to cytotoxic lymphocytes, and expression of anti-apoptotic genes (e.g., Bcl-2, Bcl-xL, X-IAP, and c-FLIP) in cancer cells from patients who relapse after treatment with this regimen.

OUTLINE: This is a multicenter study. Patients are stratified according to risk of relapse (standard [defined as ≤ 30% risk] vs high [defined as ≥ 70% risk]).

  • Nonmyeloablative conditioning regimen: Patients receive fludarabine IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1-2 hours on days -6 and -5. Patients undergo total body irradiation on day -1.
  • Allogeneic bone marrow transplantation: Patients undergo donor bone marrow infusion on day 0.
  • Post-transplantation therapy: Patients receive cyclophosphamide IV over 1-2 hours on days 3 and 4.
  • Graft-vs-host disease prophylaxis: Beginning on day 5, patients receive oral mycophenolate mofetil 3 times daily until day 35 and tacrolimus IV (then changing to orally) twice daily until day 180.

Treatment continues in the absence of disease progression.

After completion of study transplantation, patients are followed on days 30, 60, 100, and 180; at 1 year; and then annually for 4 additional years.

PROJECTED ACCRUAL: A total of 75-100 patients will be accrued for this study within 3-4 years.

Phase 2
Masking: Open Label
Primary Purpose: Treatment
  • Chronic Myeloproliferative Disorders
  • Leukemia
  • Lymphoma
  • Multiple Myeloma and Plasma Cell Neoplasm
  • Myelodysplastic Syndromes
  • Drug: cyclophosphamide
  • Drug: fludarabine phosphate
  • Drug: mycophenolate mofetil
  • Drug: tacrolimus
  • Procedure: allogeneic bone marrow transplantation
  • Radiation: radiation therapy
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Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Active, not recruiting
Not Provided
December 2015   (final data collection date for primary outcome measure)


  • Diagnosis of 1 of the following hematologic malignancies:

    • Acute leukemia

      • In second or subsequent complete remission (CR), as defined by absence of abnormal blast population by flow cytometry
      • In first CR with any of the following poor-risk cytogenetic features:

        • Alteration of chromosome 5 or 7
        • Multiple abnormalities
        • Philadelphia chromosome positive
    • Chronic phase chronic myelogenous leukemia (CML)

      • In first chronic phase and refractory to interferon alfa or imatinib mesylate
      • In second or subsequent chronic phase
    • Chronic lymphocytic leukemia, meeting 1 of the following criteria:

      • Received prior chemotherapy with a nucleoside analog and had remission lasting < 6 months
      • Received 1 prior therapy and has any of the following high-risk features:

        • Cytogenetic abnormalities of 17p, 11q
        • Mutations of the Zap70 gene
        • Somatically unmutated immunoglobulin heavy chain variable region genes
    • Hodgkin's lymphoma

      • Ineligible for autologous stem cell transplantation (SCT) due to any of the following exclusion factors:

        • LVEF < 45%
        • FEV_1 or FVC < 50% of predicted (75% of predicted in patients with prior thoracic or mantle radiotherapy)
        • Total bilirubin > 2.0 mg/dL (unless documented Gilbert's disease)
        • Creatinine > 2.0 mg/dL
    • Non-Hodgkin's lymphoma (NHL)

      • Low-grade NHL allowed provided patient had a remission duration of < 1 year after administration of any established, multi-agent chemotherapy regimen (e.g., CVP, CHOP, or rituximab in combination with CHOP)
      • Intermediate- or high-grade NHL allowed provided patient is ineligible for autologous SCT according to the criteria listed above
    • Multiple myeloma
    • Myelodysplastic syndromes
    • Paroxysmal nocturnal hemoglobinuria
    • Chronic myeloproliferative disorders other than CML, including any of the following:

      • Chronic myelomonocytic leukemia
      • Agnogenic myeloid metaplasia (or myeloid metaplasia with myelofibrosis), with hemoglobin < 10 g/dL OR WBC < 4,000/mm^3 or > 30,000/mm^3
      • Polycythemia vera or essential thrombocythemia in "spent" phase, with a history of 2 of the following:

        • Marrow fibrosis
        • Splenomegaly
        • Cytopenia (i.e., absolute neutrophil count < 1,500/mm^3, platelet count < 100,000/mm^3, hemoglobin < 10 g/dL)
      • Polycythemia vera or essential thrombocythemia with transformation to myelodysplastic syndromes or acute myeloid leukemia (requires treatment to achieve < 20% blasts in marrow)
  • No smoldering myeloma
  • Patients with acute myeloid leukemia or myelodysplastic syndromes must have had comprehensive cytogenetic evaluation of bone marrow specimen during active disease
  • Ineligible for or refused bone marrow transplantation from an HLA-matched sibling or unrelated donor
  • Ineligible for or refused autologous SCT
  • Must have an HLA mismatched (i.e., 3/6, 4/6, or 5/6) related (first-degree relative)* donor available

    • Donor ≥ 18 years of age NOTE: *Patients with an inherited recombinant HLA haplotype may receive marrow from the parent in whose gamete the recombination occurred

NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.



  • 6 months to 70 years

Performance status

  • ECOG 0-1

Life expectancy

  • Not specified


  • See Disease Characteristics


  • See Disease Characteristics
  • Bilirubin < 3.1 mg/dL


  • See Disease Characteristics


  • See Disease Characteristics
  • LVEF ≥ 35%


  • See Disease Characteristics
  • FEV_1 or FVC ≥ 40% of predicted in patients without prior thoracic or mantle radiotherapy (60% of predicted in patients with prior thoracic or mantle radiotherapy)


  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • HIV negative
  • Geographically accessible
  • No debilitating medical or psychiatric illness that would preclude giving informed consent or receiving optimal treatment or follow-up


Biologic therapy

  • See Disease Characteristics
  • No prior transfusions from donor


  • See Disease Characteristics

Endocrine therapy

  • Not specified


  • See Disease Characteristics


  • Not specified
up to 70 Years
Contact information is only displayed when the study is recruiting subjects
United States
J0457 CDR0000440990, P01CA015396, P30CA006973, JHOC-J0457, JHOC-04072704
Not Provided
Sidney Kimmel Comprehensive Cancer Center
Sidney Kimmel Comprehensive Cancer Center
National Cancer Institute (NCI)
Study Chair: Ephraim J. Fuchs, MD Sidney Kimmel Comprehensive Cancer Center
Sidney Kimmel Comprehensive Cancer Center
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP