Fludarabine Phosphate and Total-Body Radiation Followed by Donor Peripheral Blood Stem Cell Transplant and Immunosuppression in Treating Patients With Hematologic Malignancies

Sponsor
Fred Hutchinson Cancer Center (Other)
Overall Status
Completed
CT.gov ID
NCT00014235
Collaborator
National Heart, Lung, and Blood Institute (NHLBI) (NIH), National Cancer Institute (NCI) (NIH)
160
11
2
14.5

Study Details

Study Description

Brief Summary

This clinical trial studies fludarabine phosphate and total-body radiation followed by donor peripheral blood stem cell transplant and immunosuppression in treating patients with hematologic malignancies. Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving total-body irradiation together with fludarabine phosphate, cyclosporine, and mycophenolate mofetil before transplant may stop this from happening.

Condition or Disease Intervention/Treatment Phase
  • Drug: fludarabine phosphate
  • Radiation: total-body irradiation
  • Procedure: peripheral blood stem cell transplantation
  • Procedure: allogeneic hematopoietic stem cell transplantation
  • Drug: cyclosporine
  • Drug: mycophenolate mofetil
  • Other: laboratory biomarker analysis
N/A

Detailed Description

PRIMARY OBJECTIVES:
  1. To estimate the rate of grade III/IV graft-versus-host disease (GVHD) in patients treated with low-dose total body irradiation (TBI), fludarabine (fludarabine phosphate), PBSC infusion and immunosuppression with mycophenolate mofetil and a disease risk-based cyclosporine taper.

  2. To estimate the risk of graft rejection, GVHD, disease response, non-relapse mortality and the incidence and severity of infectious complications using this treatment strategy.

OUTLINE: Patients are assigned to 1 of 2 treatment groups.

ARM I (indolent disease):

CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days -4 to -2 and undergo TBI on day 0.

TRANSPLANTATION: Patients undergo donor peripheral blood stem cell transplantation (PBSCT) on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) twice daily (BID) or IV every 8-12 hours on days -3 to 56 with a taper to day 180 and mycophenolate mofetil PO BID or IV every 8-12 hours on days 0 to 27.

ARM II (aggressive disease):

CONDITIONING REGIMEN: Patients receive fludarabine phosphate and undergo TBI as in Arm I.

TRANSPLANTATION: Patients undergo donor PBSCT on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID or IV every 8-12 hours on days -3 to 56 with a taper to day 70 and mycophenolate mofetil as in Arm I.

After completion of study treatment, patients are followed up for 5 years.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
160 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Nonmyeloablative PBSC Allografting From HLA Matched Related Donors Using Fludarabine and/or Low Dose TBI With Disease-Risk Based Immunosuppression
Study Start Date :
Dec 1, 2000
Actual Primary Completion Date :
Feb 1, 2005

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm I (indolent disease)

CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. TRANSPLANTATION: Patients undergo donor PBSCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID or IV every 8-12 hours on days -3 to 56 with a taper to day 180 and mycophenolate mofetil PO BID or IV every 8-12 hours on days 0 to 27.

Drug: fludarabine phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara
  • Radiation: total-body irradiation
    Undergo TBI
    Other Names:
  • TBI
  • Procedure: peripheral blood stem cell transplantation
    Undergo PBSCT
    Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell
  • Procedure: allogeneic hematopoietic stem cell transplantation
    Undergo PBSCT

    Drug: cyclosporine
    Given PO or IV
    Other Names:
  • ciclosporin
  • cyclosporin
  • cyclosporin A
  • CYSP
  • Sandimmune
  • Drug: mycophenolate mofetil
    Given IV or PO
    Other Names:
  • Cellcept
  • MMF
  • Other: laboratory biomarker analysis
    Correlative studies

    Experimental: Arm II (aggressive disease)

    CONDITIONING REGIMEN: Patients receive fludarabine phosphate and undergo TBI as in Arm I. TRANSPLANTATION: Patients undergo donor PBSCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID or IV every 8-12 hours on days -3 to 56 with a taper to day 70 and mycophenolate mofetil as in Arm I.

    Drug: fludarabine phosphate
    Given IV
    Other Names:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara
  • Radiation: total-body irradiation
    Undergo TBI
    Other Names:
  • TBI
  • Procedure: peripheral blood stem cell transplantation
    Undergo PBSCT
    Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell
  • Procedure: allogeneic hematopoietic stem cell transplantation
    Undergo PBSCT

    Drug: cyclosporine
    Given PO or IV
    Other Names:
  • ciclosporin
  • cyclosporin
  • cyclosporin A
  • CYSP
  • Sandimmune
  • Drug: mycophenolate mofetil
    Given IV or PO
    Other Names:
  • Cellcept
  • MMF
  • Other: laboratory biomarker analysis
    Correlative studies

    Outcome Measures

    Primary Outcome Measures

    1. Probability of severe (grade III/IV) GVHD in each arm [Up to day 84]

      95% confidence interval will be calculated.

    2. Probability of severe (grade III/IV) GVHD in each arm [Up to 5 years]

      95% confidence intervals will be calculated.

    Secondary Outcome Measures

    1. Incidence of graft rejection [Day 28]

      Chimerism analysis by fluorescent in situ hybridization (FISH) or variable number tandem repeat (VNTR). Examined and reported in a descriptive manner. Confidence intervals will be presented.

    2. Incidence of graft rejection [Day 56]

      Chimerism analysis by FISH or VNTR. Examined and reported in a descriptive manner. Confidence intervals will be presented.

    3. Incidence of graft rejection [Day 84]

      Chimerism analysis by FISH or VNTR. Examined and reported in a descriptive manner. Confidence intervals will be presented.

    4. Incidence of graft rejection [Day 180]

      Chimerism analysis by FISH or VNTR. Examined and reported in a descriptive manner. Confidence intervals will be presented.

    5. Incidence of graft rejection [Day 365]

      Chimerism analysis by FISH or VNTR. Examined and reported in a descriptive manner. Confidence intervals will be presented.

    6. Incidence of non-relapse mortality [Up to 5 years]

      Examined and reported in a descriptive manner. Confidence intervals will be presented.

    7. Incidence of infectious complications [Up to 5 years]

      Examined and reported in a descriptive manner. Confidence intervals will be presented.

    8. Severity of infectious complications [Up to 5 years]

      Examined and reported in a descriptive manner. Confidence intervals will be presented.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A to 74 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Patients with non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) or multiple myeloma who are not eligible for a curative autologous transplantation or who have received a prior autologous transplantation; patients with NHL or CLL must have failed prior therapy with an alkylating agent and/or fludarabine, or be at high risk of relapse; patients with multiple myeloma must have stage II or III disease and received prior chemotherapy

    • Patients < 50 years of age with NHL, Hodgkin's disease (HD), CLL or multiple myeloma at high risk of regimen related toxicity through prior autologous transplant or through pre-existing medical conditions

    • Patients < 75 years of age with other malignant diseases treatable by allogeneic bone marrow transplant (BMT) whom through pre-existing chronic disease affecting kidneys, liver, lungs, and heart are considered to be at high risk for regimen related toxicity using standard high dose regimens; the following diseases are the likely candidates

    • Myelodysplastic syndromes

    • Myeloproliferative syndromes

    • Acute Leukemia with < 10% blasts

    • Amyloidosis

    • Hodgkin's disease

    • The Fred Hutchinson Cancer Research Center (FHCRC) Patient Care Conference (PCC) may approve patients with other malignancies or patients declining standard allografts for transplant following presentation and approval; centers outside the FHCRC that have a PCC or equivalent should obtain their Institutional approval; if there is not a comparable group at the Institution, please contact the FHCRC Principal Investigator for FHCRC approval through PCC

    • DONOR: Human leukocyte antigen (HLA) genotypically or phenotypically identical related donor

    • DONOR: Donor must consent to filgrastim (G-CSF) administration and leukapheresis

    • DONOR: Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian)

    Exclusion Criteria:
    • Eligible for a high-priority curative autologous transplant

    • Patients with rapidly progressive aggressive NHL unless in minimal disease state

    • Any current central nervous system (CNS) involvement with disease

    • Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment

    • Females who are pregnant

    • Patients who are human immunodeficiency virus (HIV) positive

    • Cardiac ejection fraction < 40%; ejection fraction is required if the patient has a history of anthracyclines or history of cardiac disease

    • Receiving supplementary continuous oxygen

    • Diffusing capacity of the lung for carbon monoxide (DLCO) < 30%

    • Total lung capacity (TLC) < 30%

    • Forced expiratory volume in one second (FEV1) < 30%

    • Total bilirubin > 2x the upper limit of normal

    • Serum glutamate pyruvate transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT) 4x the upper limit of normal

    • Karnofsky score < 50

    • Patients with poorly controlled hypertension who are unable to have blood pressure kept below 150/90 on standard medication

    • Patients with renal failure are eligible, however patients with renal compromise (serum creatinine greater than 2.0) will likely have further compromise in renal function and may require hemodialysis (which may be permanent) due to the need to maintain adequate serum cyclosporine levels

    • The addition of cytotoxic agents for "cytoreduction" with the exception of hydroxyurea and imatinib mesylate will not be allowed within two weeks of the initiation of conditioning

    • DONOR: Identical twin

    • DONOR: Age less than 12 years

    • DONOR: Pregnancy

    • DONOR: Infection with HIV

    • DONOR: Inability to achieve adequate venous access

    • DONOR: Known allergy to G-CSF

    • DONOR: Current serious systemic illness

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Arizona Health Sciences Center Tucson Arizona United States 85724
    2 City of Hope Medical Center Duarte California United States 91010
    3 Stanford University Hospitals and Clinics Stanford California United States 94305
    4 OHSU Knight Cancer Institute Portland Oregon United States 97239
    5 Baylor University Medical Center Dallas Texas United States 75246
    6 Huntsman Cancer Institute/University of Utah Salt Lake City Utah United States 84112
    7 LDS Hospital Salt Lake City Utah United States 84143
    8 Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Seattle Washington United States 98109
    9 Froedtert Hospital Milwaukee Wisconsin United States 53226-3596
    10 Universitaet Leipzig Leipzig Germany D-04103
    11 University of Torino Torino Italy 10126

    Sponsors and Collaborators

    • Fred Hutchinson Cancer Center
    • National Heart, Lung, and Blood Institute (NHLBI)
    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: David Maloney, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Fred Hutchinson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT00014235
    Other Study ID Numbers:
    • 1596.00
    • NCI-2012-00671
    • 1596.00
    • P30CA015704
    First Posted:
    Jan 27, 2003
    Last Update Posted:
    Jan 21, 2020
    Last Verified:
    Jan 1, 2020

    Study Results

    No Results Posted as of Jan 21, 2020