Skip to content
Triangle logo TriangleGet started
← Study library

NCT00075478 · REGISTRY CONDITION SEARCH

Total-Body Irradiation With or Without Fludarabine Phosphate Followed By Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase
PHASE3
Status at capture
COMPLETED
Registry last update
2017-05-15

This randomized phase III trial is studying total-body irradiation (TBI) and fludarabine phosphate to see how it works compared with TBI alone followed by donor stem cell transplant in treating patients with hematologic cancer. Giving low doses of chemotherapy, such as fludarabine phosphate, and radiation therapy before a donor 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 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 cyclosporine and mycophenolate mofetil after transplant may stop this from happening. It is not yet known whether TBI followed by donor stem cell transplant is more effective with or without fludarabine phosphate in treating hematologic cancer.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

→

baseline

Baseline characteristics

→

outcome · POSTED

Overall Survival

→

outcome · POSTED

Incidence of Non-relapse Mortality

→

outcome · POSTED

Incidence of Relapse/Progression

→

outcome · POSTED

Incidence of Relapse-related Mortality

→

outcome · POSTED

Incidence of Grades II-IV Acute GVHD

→

outcome · POSTED

Incidence of Chronic Extensive GVHD

→

outcome · POSTED

Incidence of Graft Rejection

→

outcome · POSTED

Progression-free Survival

→

adverse events

Adverse events

→

more info

Limitations, agreements, and source contact

→
Who could take part
eligibility Criteria
Inclusion Criteria: * Patients must be not eligible for conventional allogeneic hematopoietic cell transplantation (HCT) and must have disease expected to be stable for at least 100 days without chemotherapy * An autograft immediately prior (less than 6 months) to nonmyeloablative HCT (tandem approach) is not permitted * Patients with hematologic malignancies treatable with HCT or with a B cell malignancy except those curable with autologous transplant will be included * Aggressive non-Hodgkin lymphomas (NHLs) and other histologies such as diffuse large B cell NHL: patients are eligible IF they are not eligible for autologous hematopoietic stem cell transplantation (HSCT), not eligible for conventional myeloablative HSCT, or have failed an autologous HSCT * Low grade NHL with \< 6 month duration of complete remission (CR) between courses of conventional therapy * Mantle cell NHL; may be treated in first CR * Chronic lymphocytic leukemia (CLL) must have either: * Failed to meet National Cancer Institute (NCI) Working Group criteria for complete or partial response after therapy with a regimen containing fludarabine phosphate (FLU) (or another nucleoside analog, e.g. cladribine \[2-CDA\], pentostatin) or experience disease relapse within 12 months after completing therapy with a regimen containing FLU (or another nucleoside analog) * Failed FLU-cyclophosphamide \[CY\]-rituximab (FCR) combination chemotherapy at any time point * Have "17p deletion" cytogenetic abnormality; patients should have received induction chemotherapy but could be transplanted in 1st CR * Or patients with a diagnosis of CLL (or small lymphocytic lymphoma) or diagnosis of CLL that progresses to prolymphocytic leukemia (PLL), or T-cell CLL or PLL * Hodgkin lymphoma (HL): must have received and failed frontline therapy; patients must have failed or were not eligible for autologous transplant * Multiple myeloma (MM): must have chemosensitive disease after failed autografting (an autografting immediately prior \[within 6 months\] to nonmyeloablative HCT \[tandem approach\] is not permitted) * Acute myeloid leukemia (AML): must have \< 5% marrow blasts at the time of transplant and be beyond first CR * Acute lymphocytic leukemia (ALL): must have \< 5% marrow blasts at the time of transplant and be beyond first CR * Chronic myelogenous leukemia (CML): patients will be accepted in chronic phase (CP) beyond CP1 if they have received previous myelosuppressive chemotherapy or HCT, \< 5% marrow blasts at time of transplant * Myelodysplastic syndromes (MDS)/myeloproliferative disorders (MPD): must have received previous myelosuppressive chemotherapy or HCT, \< 5% marrow blasts at time of transplant * Waldenstroms Macroglobulinemia: must have failed 2 courses of therapy * Patients will not be allowed to receive myelosuppressive chemotherapy for three weeks prior to conditioning * Patients \< 12 years old must be approved by both the participating institutions' patient review committee such as the Patient Care Conference (PCC) at the Fred Hutchinson Cancer Research Center (FHCRC) and the FHCRC principal investigator * Patients who refused to be treated on a conventional HCT protocol; for this inclusion criterion, transplants must be approved by both the participating institution's patient review committee such as the Patient Care Conference (PCC) at the FHCRC and the FHCRC principal investigator * Patients with human leukocyte antigen (HLA)-matched related donors * DONOR: Related donor who is HLA genotypically identical at least at one haplotype and may be phenotypically or genotypically identical at the allele level at HLA-A, -B, -C, -DRB1, and -DQB1 * 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) * DONOR: For females of child bearing age, serum pregnancy qualitative (PGSTAT) within 72 hours prior to initial dose of filgrastim (G-CSF); results must be available prior to filgrastim Exclusion Criteria: * Eligible for a high priority curative autologous transplant * Patients with rapidly progressive, aggressive NHL unless in minimal disease state * Patients with chronic myelomonocytic leukemia * Presence of circulating leukemic blasts (in the peripheral blood) detected by standard pathology for patients with AML, ALL or CML * Life expectancy severely limited by diseases other than malignancy * Any current central nervous system (CNS) involvement with disease refractory to intrathecal chemotherapy * Fertile men or women unwilling to use contraceptives during and for up to 12 months post treatment * Female patients who are pregnant or breastfeeding * Human immunodeficiency virus (HIV) positive patients * Patients with active non-hematological malignancies (except localized non-melanoma skin malignancies) * Patients with a history of non-hematologic malignancies (except non-melanoma skin cancers) currently in a complete remission, who are less than 5 years from the time of complete remission, and have a \> 20% risk of disease recurrence * Fungal infections with radiological progression after receipt of amphotericin formulation or mold-active azoles for greater than 1 month * Patients with active bacterial or fungal infections unresponsive to medical therapy * Karnofsky score \< 50 for adult patients * Lansky-Play performance score \< 50 for pediatric patients * The addition of cytotoxic agents for "cytoreduction" with the exception of tyrosine kinase inhibitors (imatinib mesylate), cytokine therapy, hydroxyurea, low dose cytarabine, chlorambucil, or rituxan will not be allowed within three weeks of the initiation of conditioning * Patients with the following organ dysfunction: * Symptomatic coronary artery disease or ejection fraction \< 35% or other cardiac failure requiring therapy (required for patients with history of cardiac disease or anthracycline use); ejection fraction is required if age \> 50 years or there is a history of anthracycline exposure or history of cardiac disease * Poorly controlled hypertension on multiple antihypertensives * Pulmonary: diffusion capacity of carbon monoxide (DLCO) \< 30%, total lung capacity (TLC) \< 30%, forced expiratory volume in one second (FEV1) \< 30% and/or receiving supplementary continuous oxygen; the FHCRC study principal investigator (PI) must approve enrollment of all patients with pulmonary nodules * Liver function abnormalities: patients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function, bridging fibrosis, and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin \> 3 mg/dL, and symptomatic biliary disease * DONOR: Age less than 12 years * DONOR: Identical twin * DONOR: Pregnancy * DONOR: Infection with HIV * DONOR: Known allergy to filgrastim * DONOR: Current serious systemic illness that would result in increased risk for filgrastim mobilization and harvest of PBSC
healthy Volunteers
false
maximum Age
75 Years
sex
ALL
std Ages
  1. CHILD
  2. ADULT
  3. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    Patients receive fludarabine phosphate IV on days -4 to -2. Patients then undergo low-dose TBI on day 0. After TBI, patients undergo PBSCT on day 0. Patients receive cyclosporine PO BID on days -3 to 56 in the absence of GVHD. Patients with no evidence of GVHD at day 56 begin a cyclosporine taper and continue the taper until day 180. Patients with evidence of disease progression and no evidence of GVHD prior to day 56 receive tapered doses of cyclosporine for 2 weeks. Patients also receive MMF PO BID on days 0-28 in the absence of GVHD. If treatment for GVHD is required before day 28, MMF is continued until a steroid taper begins.
    intervention Names
    1. Procedure: Total-Body Irradiation
    2. Drug: Fludarabine Phosphate
    3. Drug: Mycophenolate Mofetil
    4. Drug: Cyclosporine
    5. Procedure: Peripheral Blood Stem Cell Transplantation
    label
    Arm I (chemotherapy, TBI, transplant, GVHD prophylaxis)
    type
    EXPERIMENTAL
  2. description
    Patients undergo low-dose TBI on day 0. After TBI, patients undergo PBSCT on day 0. Patients receive cyclosporine PO BID on days -3 to 56 in the absence of GVHD. Patients with no evidence of GVHD at day 56 begin a cyclosporine taper and continue the taper until day 180. Patients with evidence of disease progression and no evidence of GVHD prior to day 56 receive tapered doses of cyclosporine for 2 weeks. Patients also receive MMF PO BID on days 0-28 in the absence of GVHD. If treatment for GVHD is required before day 28, MMF is continued until a steroid taper begins.
    intervention Names
    1. Procedure: Total-Body Irradiation
    2. Drug: Mycophenolate Mofetil
    3. Drug: Cyclosporine
    4. Procedure: Peripheral Blood Stem Cell Transplantation
    label
    Arm II (TBI, transplant, GVHD prophylaxis)
    type
    ACTIVE_COMPARATOR
interventions
  1. arm Group Labels
    1. Arm I (chemotherapy, TBI, transplant, GVHD prophylaxis)
    2. Arm II (TBI, transplant, GVHD prophylaxis)
    description
    Undergo TBI
    name
    Total-Body Irradiation
    other Names
    1. TBI
    2. Total Body Irradiation
    3. Whole-Body Irradiation
    type
    PROCEDURE
  2. arm Group Labels
    1. Arm I (chemotherapy, TBI, transplant, GVHD prophylaxis)
    description
    Given IV
    name
    Fludarabine Phosphate
    other Names
    1. 2-F-ara-AMP
    2. Beneflur
    3. SH T 586
    type
    DRUG
  3. arm Group Labels
    1. Arm I (chemotherapy, TBI, transplant, GVHD prophylaxis)
    2. Arm II (TBI, transplant, GVHD prophylaxis)
    description
    Given PO
    name
    Mycophenolate Mofetil
    other Names
    1. Cellcept
    2. MMF
    type
    DRUG
  4. arm Group Labels
    1. Arm I (chemotherapy, TBI, transplant, GVHD prophylaxis)
    2. Arm II (TBI, transplant, GVHD prophylaxis)
    description
    Given PO
    name
    Cyclosporine
    other Names
    1. 27-400
    2. CsA
    3. Neoral
    4. OL 27-400
    5. Sandimmun
    type
    DRUG
  5. arm Group Labels
    1. Arm I (chemotherapy, TBI, transplant, GVHD prophylaxis)
    2. Arm II (TBI, transplant, GVHD prophylaxis)
    description
    Undergo transplantation
    name
    Peripheral Blood Stem Cell Transplantation
    other Names
    1. PBPC transplantation
    2. Peripheral Blood Progenitor Cell Transplantation
    3. Peripheral Stem Cell Support
    4. Peripheral Stem Cell Transplantation
    type
    PROCEDURE
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
87
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    Percentage of patients surviving as estimated by Kaplan-Meier.
    measure
    Overall Survival
    time Frame
    3 years after transplant
secondary Outcomes
  1. description
    Percentage of NRM as estimated by cumulative incidence methods with competing risks
    measure
    Incidence of Non-relapse Mortality
    time Frame
    3 years after transplant
  2. description
    Percentage of relapse estimated by cumulative incidence methods
    measure
    Incidence of Relapse/Progression
    time Frame
    3 years after transplant
  3. description
    Percentage of death following relapse/progression, estimated by cumulative incidence methods
    measure
    Incidence of Relapse-related Mortality
    time Frame
    3 years after transplant
  4. description
    Percentage patients with grades II-IV GHVD, estimated by cumulative incidence methods
    measure
    Incidence of Grades II-IV Acute GVHD
    time Frame
    120 days after transplant
  5. description
    Percentage patients with chronic extensive GVHD, estimated by cumulative incidence methods
    measure
    Incidence of Chronic Extensive GVHD
    time Frame
    3 years after transplant
  6. description
    Donor CD3 chimerism less than 5%
    measure
    Incidence of Graft Rejection
    time Frame
    1 year after transplant
  7. description
    Percentage of patients with progression-free survival, estimated by cumulative incidence methods
    measure
    Progression-free Survival
    time Frame
    3 years after transplant
Full study description
brief Summary
This randomized phase III trial is studying total-body irradiation (TBI) and fludarabine phosphate to see how it works compared with TBI alone followed by donor stem cell transplant in treating patients with hematologic cancer. Giving low doses of chemotherapy, such as fludarabine phosphate, and radiation therapy before a donor 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 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 cyclosporine and mycophenolate mofetil after transplant may stop this from happening. It is not yet known whether TBI followed by donor stem cell transplant is more effective with or without fludarabine phosphate in treating hematologic cancer.
detailed Description
PRIMARY OBJECTIVES: I. To compare overall survival at 3 years after conditioning with 200 cGy TBI alone vs. fludarabine (fludarabine phosphate)/200 cGy TBI in heavily pretreated patients with hematologic malignancies at low/moderate risk for graft rejection. SECONDARY OBJECTIVES: I. To compare the non-relapse mortality 1-year after conditioning in patients who received TBI alone vs. fludarabine/TBI. II. To compare the incidences of graft rejection in patients who received TBI alone vs. fludarabine/TBI. III. To compare the incidences of grades II-IV acute graft-versus-host disease (GVHD) and chronic extensive GVHD. IV. To compare rates of disease progression and/or relapse-related mortality. V. To compare the immune reconstitution and the risks of infections. OUTLINE: NONMYELOABLATIVE CONDITIONING REGIMEN: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive fludarabine phosphate intravenously (IV) on days -4 to -2. Patients then undergo low-dose TBI on day 0. ARM II: Patients undergo low-dose TBI on day 0. ALLOGENEIC PERIPHERAL BLOOD STEM CELL TRANSPLANTATION (PBSCT): After TBI, patients undergo PBSCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) twice daily (BID) on days -3 to 56 in the absence of GVHD. Patients with no evidence of GVHD at day 56 begin a cyclosporine taper and continue the taper until day 180. Patients with evidence of disease progression and no evidence of GVHD prior to day 56 receive tapered doses of cyclosporine for 2 weeks. Patients also receive mycophenolate mofetil (MMF) PO BID on days 0-28 in the absence of GVHD. If treatment for GVHD is required before day 28, MMF is continued until a steroid taper begins. Patients are followed up periodically for 1.5 years and then annually for 5 years post-transplantation.
Source references
references
  1. citation
    Kornblit B, Maloney DG, Storb R, Storek J, Hari P, Vucinic V, Maziarz RT, Chauncey TR, Pulsipher MA, Bruno B, Petersen FB, Bethge WA, Hubel K, Bouvier ME, Fukuda T, Storer BE, Sandmaier BM. Fludarabine and 2-Gy TBI is superior to 2 Gy TBI as conditioning for HLA-matched related hematopoietic cell transplantation: a phase III randomized trial. Biol Blood Marrow Transplant. 2013 Sep;19(9):1340-7. doi: 10.1016/j.bbmt.2013.06.002. Epub 2013 Jun 11.
    pmid
    23769990
    type
    BACKGROUND
  2. citation
    Cooper JP, Storer BE, Granot N, Gyurkocza B, Sorror ML, Chauncey TR, Shizuru J, Franke GN, Maris MB, Boyer M, Bruno B, Sahebi F, Langston AA, Hari P, Agura ED, Lykke Petersen S, Maziarz RT, Bethge W, Asch J, Gutman JA, Olesen G, Yeager AM, Hubel K, Hogan WJ, Maloney DG, Mielcarek M, Martin PJ, Flowers MED, Georges GE, Woolfrey AE, Deeg JH, Scott BL, McDonald GB, Storb R, Sandmaier BM. Allogeneic hematopoietic cell transplantation with non-myeloablative conditioning for patients with hematologic malignancies: Improved outcomes over two decades. Haematologica. 2021 Jun 1;106(6):1599-1607. doi: 10.3324/haematol.2020.248187.
    pmid
    32499241
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
    1. release id
      ctgov-registry-1336d216cbd1bbff780dac70
      edge id
      nct-edge-8762049c08929db7bcc2
      requested nct id
      NCT00075478
      primary nct id
      NCT00075478
      source kind
      ctgov_condition_query
      source record id
      Source null
      source file sha256
      2314ce01316b2d7044d298c6d25eda12e99cc5f44273bc75efed6cd5e03a8c14
      payload sha256
      d48a554687c7e56a38fa3eec2a128e596d0909d8bd394db0a4d406a44cb9fb0d
      payload
      clinical indication matching status
      condition_index_match_asserted_by_registry_not_reviewed
      end exclusive
      true
      id
      nct-edge-8762049c08929db7bcc2
      link basis
      returned_by_explicit_condition_and_posted_results_filter_query
      nct id
      NCT00075478
      occurrences
      1. context exact
        NCT00075478
        end
        11
        exact text
        NCT00075478
        start
        0
      offset unit
      unicode_code_points
      query cond
      Plasma Cell Neoplasms
      query disease state id
      ds-plasma-cell-neoplasms
      source file
      /Users/arunverma/Documents/ChatGPT/Cancer Statistics Website/research-data/2026-09-10/clinicaltrials-condition/round-0000/raw/cond-plasma-cell-neoplasms-000.json
      source file sha256
      2314ce01316b2d7044d298c6d25eda12e99cc5f44273bc75efed6cd5e03a8c14
      source json pointer
      /studies/760/protocolSection/identificationModule/nctId
      source kind
      ctgov_condition_query
      source record id
      Source null
      source string basis
      parsed_JSON_string_unmodified
      source string sha256
      4ac5c078cf353e84f6e8b35d1182f12d5f4444cf336d9a414f86f3873ae5b367

    Preserved source evidence · Not medical advice