Fludarabine Phosphate, Cyclophosphamide, and Total-Body Irradiation Followed by Donor Bone Marrow Transplant, Mycophenolate Mofetil, and Cyclosporine in Treating Patients With Fanconi Anemia

Sponsor
Fred Hutchinson Cancer Center (Other)
Overall Status
Completed
CT.gov ID
NCT00453388
Collaborator
National Cancer Institute (NCI) (NIH), National Heart, Lung, and Blood Institute (NHLBI) (NIH)
6
5
4
76
1.2
0

Study Details

Study Description

Brief Summary

This phase II trial studies how well total-body irradiation (TBI) works when given together with fludarabine phosphate and cyclophosphamide followed by donor bone marrow transplant, mycophenolate mofetil, and cyclosporine in treating patients with Fanconi anemia (FA). Giving low doses of chemotherapy, such as fludarabine phosphate and cyclophosphamide, and TBI before or after a donor bone marrow transplant helps stop the growth of abnormal cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune 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 mycophenolate mofetil and cyclosporine after the transplant may stop this from happening.

Condition or Disease Intervention/Treatment Phase
  • Procedure: Allogeneic Bone Marrow Transplantation
  • Drug: Cyclophosphamide
  • Drug: Cyclosporine
  • Drug: Fludarabine Phosphate
  • Other: Laboratory Biomarker Analysis
  • Drug: Mycophenolate Mofetil
  • Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation
  • Radiation: Total-Body Irradiation
Phase 2

Detailed Description

PRIMARY OBJECTIVES:
  1. Identify doses of total-body irradiation (TBI) that lead to sufficient probability of donor engraftment (> 5% donor cluster of differentiation [CD]3 chimerism) by day +200.

  2. Evaluate the probability of severe acute graft-versus-host disease.

SECONDARY OBJECTIVES:
  1. Evaluate the probabilities of overall survival, regimen-related toxicity (RRT), and recurrent hematopoietic malignancy in those patients with a prior underlying history of such.

  2. Examine the degree to which mixed chimerism provides for amelioration of symptoms (i.e., infections due to neutropenia, hemorrhage due to thrombocytopenia) associated with bone marrow failure.

  3. Determine if the FA complementation group and % initial mosaicism predict engraftment and RRT outcomes.

OUTLINE: Patients are assigned to 1 of 4 treatment arms.

NOTE: Patients no longer receive pre-transplant cyclophosphamide as of February 2009.

After completion of study treatment, patients are followed up at 6 months and then annually thereafter.

Study Design

Study Type:
Interventional
Actual Enrollment :
6 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Nonmyeloablative Hematopoietic Cell Transplantation for Patients With Fanconi Anemia Using Alternative Marrow Donors: A Phase II Dose-Finding Study
Actual Study Start Date :
Feb 1, 2007
Actual Primary Completion Date :
Jun 1, 2013
Actual Study Completion Date :
Jun 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm I (2 vs 2.5 vs 3 Gy TBI dose-escalation)

Patients with a history of hematologic malignancy and HLA-haploidentical donor receive fludarabine phosphate (FLU) intravenously (IV) over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF orally (PO) thrice daily (TID) on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD.

Procedure: Allogeneic Bone Marrow Transplantation
Undergo allogeneic bone marrow transplant
Other Names:
  • Allo BMT
  • Allogeneic BMT
  • Drug: Cyclophosphamide
    Given IV
    Other Names:
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
  • Drug: Cyclosporine
    Given IV or PO
    Other Names:
  • 27-400
  • Ciclosporin
  • CsA
  • Cyclosporin
  • Cyclosporin A
  • Neoral
  • OL 27-400
  • Sandimmun
  • Sandimmune
  • SangCya
  • Drug: Fludarabine Phosphate
    Given IV
    Other Names:
  • 2-F-ara-AMP
  • 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
  • Beneflur
  • Fludara
  • Oforta
  • SH T 586
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Drug: Mycophenolate Mofetil
    Given PO
    Other Names:
  • Cellcept
  • MMF
  • Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation
    Undergo allogeneic stem cell transplant
    Other Names:
  • Non-myeloablative allogeneic transplant
  • Nonmyeloablative Stem Cell Transplantation
  • NST
  • Radiation: Total-Body Irradiation
    Undergo TBI
    Other Names:
  • TOTAL BODY IRRADIATION
  • Whole-Body Irradiation
  • Experimental: Arm II (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI de-escalation)

    Patients with no history of hematological malignancy and HLA-haploidentical donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD.

    Procedure: Allogeneic Bone Marrow Transplantation
    Undergo allogeneic bone marrow transplant
    Other Names:
  • Allo BMT
  • Allogeneic BMT
  • Drug: Cyclophosphamide
    Given IV
    Other Names:
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
  • Drug: Cyclosporine
    Given IV or PO
    Other Names:
  • 27-400
  • Ciclosporin
  • CsA
  • Cyclosporin
  • Cyclosporin A
  • Neoral
  • OL 27-400
  • Sandimmun
  • Sandimmune
  • SangCya
  • Drug: Fludarabine Phosphate
    Given IV
    Other Names:
  • 2-F-ara-AMP
  • 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
  • Beneflur
  • Fludara
  • Oforta
  • SH T 586
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Drug: Mycophenolate Mofetil
    Given PO
    Other Names:
  • Cellcept
  • MMF
  • Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation
    Undergo allogeneic stem cell transplant
    Other Names:
  • Non-myeloablative allogeneic transplant
  • Nonmyeloablative Stem Cell Transplantation
  • NST
  • Radiation: Total-Body Irradiation
    Undergo TBI
    Other Names:
  • TOTAL BODY IRRADIATION
  • Whole-Body Irradiation
  • Experimental: Arm III (2 vs 2.5 vs 3 Gy TBI dose-escalation)

    Patients with history of hematologic malignancy and HLA-matched unrelated donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD.

    Procedure: Allogeneic Bone Marrow Transplantation
    Undergo allogeneic bone marrow transplant
    Other Names:
  • Allo BMT
  • Allogeneic BMT
  • Drug: Cyclophosphamide
    Given IV
    Other Names:
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
  • Drug: Cyclosporine
    Given IV or PO
    Other Names:
  • 27-400
  • Ciclosporin
  • CsA
  • Cyclosporin
  • Cyclosporin A
  • Neoral
  • OL 27-400
  • Sandimmun
  • Sandimmune
  • SangCya
  • Drug: Fludarabine Phosphate
    Given IV
    Other Names:
  • 2-F-ara-AMP
  • 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
  • Beneflur
  • Fludara
  • Oforta
  • SH T 586
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Drug: Mycophenolate Mofetil
    Given PO
    Other Names:
  • Cellcept
  • MMF
  • Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation
    Undergo allogeneic stem cell transplant
    Other Names:
  • Non-myeloablative allogeneic transplant
  • Nonmyeloablative Stem Cell Transplantation
  • NST
  • Radiation: Total-Body Irradiation
    Undergo TBI
    Other Names:
  • TOTAL BODY IRRADIATION
  • Whole-Body Irradiation
  • Experimental: Arm IV (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI de-escalation)

    Patients with no history of hematological malignancy and HLA-matched unrelated donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD.

    Procedure: Allogeneic Bone Marrow Transplantation
    Undergo allogeneic bone marrow transplant
    Other Names:
  • Allo BMT
  • Allogeneic BMT
  • Drug: Cyclophosphamide
    Given IV
    Other Names:
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
  • Drug: Cyclosporine
    Given IV or PO
    Other Names:
  • 27-400
  • Ciclosporin
  • CsA
  • Cyclosporin
  • Cyclosporin A
  • Neoral
  • OL 27-400
  • Sandimmun
  • Sandimmune
  • SangCya
  • Drug: Fludarabine Phosphate
    Given IV
    Other Names:
  • 2-F-ara-AMP
  • 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
  • Beneflur
  • Fludara
  • Oforta
  • SH T 586
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Drug: Mycophenolate Mofetil
    Given PO
    Other Names:
  • Cellcept
  • MMF
  • Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation
    Undergo allogeneic stem cell transplant
    Other Names:
  • Non-myeloablative allogeneic transplant
  • Nonmyeloablative Stem Cell Transplantation
  • NST
  • Radiation: Total-Body Irradiation
    Undergo TBI
    Other Names:
  • TOTAL BODY IRRADIATION
  • Whole-Body Irradiation
  • Outcome Measures

    Primary Outcome Measures

    1. Number of Patients Who Engraft at Each Dose of TBI Used [Up to Day 200]

      Number of subjects who engrafted. Engraftment defined as greater than 95% donor chimerism.

    2. Incidence of Grades III-IV Acute GVHD [Up to Day 100]

      Number of subjects who developed maximum grade acute graft-vs-host disease aGVHD Stages Skin: - a maculopapular eruption involving < 25% BSA - a maculopapular eruption involving 25 - 50% BSA - generalized erythroderma - generalized erythroderma with bullous formation and often with desquamation Liver: - bilirubin 2.0 - 3.0 mg/100 mL - bilirubin 3 - 5.9 mg/100 mL - bilirubin 6 - 14.9 mg/100 mL - bilirubin > 15 mg/100 mL Gut: Diarrhea is graded 1 - 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients with visible bloody diarrhea are at least stage 2 gut and grade 3 overall. aGVHD Grades Grade III: Stage 2 - 4 gastrointestinal involvement and/or +2 to +4 liver involvement, with or without a rash Grade IV: Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death

    Secondary Outcome Measures

    1. Incidence of Transplant-related Mortality [Up to Day 200]

      Number of subjects who expired due to transplant-related mortality

    2. Incidence of Adverse Events [Up to Day 100]

      Number of subjects who developed reportable AEs, assessed using adapted version of the Common Toxicity Criteria

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Any patient with FA and bone marrow (BM) failure involving 2 of the following 3 lineages: granulocyte count < 0.5 x 109/L, platelet count < 20 x 109/L, or hemoglobin < 8 g/dL

    • Any patient with FA who requires red blood cell or platelet transfusions because of marrow failure

    • Any patient with FA who has a life-threatening BM failure involving a single hematopoietic lineage

    • Any patient with FA and pre-existing cytogenetic abnormality including hematopoietic malignancy (acute myeloid leukemia [AML] or myelodysplastic syndrome [MDS]) in morphological remission (defined as absence of circulating blasts and bone marrow blasts < 5% as assessed by morphology); Note that hematopoietic recovery is not required for remission status

    • Patients must have a negative cytotoxic cross match with donor

    • DONOR: Related, human leukocyte antigen (HLA)-haploidentical donors must be identical for one HLA haplotype and mismatched for any number of HLA-A, -B, -C, DRB1 or DQB1 loci of the unshared haplotype

    • DONOR: Unrelated, HLA-matched donors must be matched at HLA-A, B, C, DRB1 and DQB1 by deoxyribonucleic acid (DNA) typing at the highest resolution routinely available at the time of donor selection; a single allele mismatch at HLA-A, B, or C is allowed OR a single DQB1 mismatch is allowed

    • DONOR: Bone marrow will be the only allowed hematopoietic stem cell source

    • DONOR: Haploidentical donor selection will be based on standard institutional criteria, otherwise no specific prioritization will be made amongst the suitable available donors

    Exclusion Criteria:
    • Patients having available HLA-matched related donors

    • Significant organ dysfunction that would prevent compliance with conditioning, graft-versus-host disease (GVHD) prophylaxis, or would severely limit the probability of survival, such as liver disease/failure (active hepatitis, moderate to severe portal fibrosis/cirrhosis confirmed by biopsy or uncorrectable hepatic synthetic dysfunction), lung disease, or cardiac disease (ejection fraction < 35%, or if unable to obtain ejection fraction, shortening fraction of < 26%; if shortening is < 26% a cardiology consult is required with principal investigator [PI] having final approval of eligibility)

    • Human immunodeficiency virus (HIV) seropositive patients

    • Fertile females who are unwilling to use contraceptive techniques during and for the twelve months following treatment, as well as females who are pregnant or actively breast feeding

    • Fertile males who are unwilling to use contraceptive techniques during and for the twelve months following treatment

    • AML/MDS in morphological relapse, defined as having circulating blasts or bone marrow blasts >= 5% as assessed by morphology

    • Active infectious disease concerns

    • Karnofsky performance score < 50 or Lansky performance score < 40

    • DONOR: Donors found to have Fanconi anemia based on chromosomal breakage analysis

    • DONOR: Donors who are not expected to meet the minimum target dose of marrow cells (1 x 10^8 nucleated cells/kg recipient ideal body weight [IBW]) or who are unwilling to be bone marrow donors

    • DONOR: HIV-positive donors

    • DONOR: Donors who are cross-match positive with recipient

    • DONOR: Recipient homozygous at mismatched locus; if the recipient is homozygous at HLA-A, B, or C and the donor is mismatched at that locus, the donor should be avoided; exceptions must be discussed with the PI

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Children's Hospital and Research Center at Oakland Oakland California United States 94609-1809
    2 Vanderbilt University/Ingram Cancer Center Nashville Tennessee United States 37232
    3 Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Seattle Washington United States 98109
    4 Children's Hospital of Wisconsin Milwaukee Wisconsin United States 53201
    5 Universidade Federal do ParanĂ¡ Curitiba ParanĂ¡ Brazil 80060-000

    Sponsors and Collaborators

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

    Investigators

    • Principal Investigator: Hans-Peter Kiem, 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:
    NCT00453388
    Other Study ID Numbers:
    • 2064.00
    • NCI-2010-00238
    • 2064.00
    • P30CA015704
    First Posted:
    Mar 28, 2007
    Last Update Posted:
    Jan 29, 2020
    Last Verified:
    Dec 1, 2019

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Arm I (2 vs 2.5 vs 3 Gy TBI Dose-escalation) Arm II (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation) Arm III (2 vs 2.5 vs 3 Gy TBI Dose-escalation) Arm IV (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation)
    Arm/Group Description Patients with a history of hematologic malignancy and HLA-haploidentical donor receive fludarabine phosphate (FLU) intravenously (IV) over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF orally (PO) thrice daily (TID) on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI Patients with no history of hematological malignancy and HLA-haploidentical donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI Patients with history of hematologic malignancy and HLA-matched unrelated donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI Patients with no history of hematological malignancy and HLA-matched unrelated donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI
    Period Title: Overall Study
    STARTED 0 5 1 0
    COMPLETED 0 5 1 0
    NOT COMPLETED 0 0 0 0

    Baseline Characteristics

    Arm/Group Title Arm I (2 vs 2.5 vs 3 Gy TBI Dose-escalation) Arm II (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation) Arm III (2 vs 2.5 vs 3 Gy TBI Dose-escalation) Arm IV (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation) Total
    Arm/Group Description Patients with a history of hematologic malignancy and HLA-haploidentical donor receive fludarabine phosphate (FLU) intravenously (IV) over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF orally (PO) thrice daily (TID) on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI Patients with no history of hematological malignancy and HLA-haploidentical donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI Patients with history of hematologic malignancy and HLA-matched unrelated donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI Patients with no history of hematological malignancy and HLA-matched unrelated donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI Total of all reporting groups
    Overall Participants 0 5 1 0 6
    Age (Count of Participants)
    <=18 years
    5
    Infinity
    1
    20%
    6
    600%
    Between 18 and 65 years
    0
    NaN
    0
    0%
    0
    0%
    >=65 years
    0
    NaN
    0
    0%
    0
    0%
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    11.1
    11.9
    11.1
    Sex: Female, Male (Count of Participants)
    Female
    5
    Infinity
    0
    0%
    5
    500%
    Male
    0
    NaN
    1
    20%
    1
    100%
    Region of Enrollment (participants) [Number]
    United States
    3
    Infinity
    1
    20%
    4
    400%
    Brazil
    2
    Infinity
    0
    0%
    2
    200%

    Outcome Measures

    1. Primary Outcome
    Title Number of Patients Who Engraft at Each Dose of TBI Used
    Description Number of subjects who engrafted. Engraftment defined as greater than 95% donor chimerism.
    Time Frame Up to Day 200

    Outcome Measure Data

    Analysis Population Description
    No subjects meeting the criteria for Arms I or IV were enrolled.
    Arm/Group Title Arm I (2 vs 2.5 vs 3 Gy TBI Dose-escalation) Arm II (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation) Arm III (2 vs 2.5 vs 3 Gy TBI Dose-escalation) Arm IV (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation)
    Arm/Group Description Patients with a history of hematologic malignancy and HLA-haploidentical donor receive fludarabine phosphate (FLU) intravenously (IV) over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF orally (PO) thrice daily (TID) on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI Patients with no history of hematological malignancy and HLA-haploidentical donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI Patients with history of hematologic malignancy and HLA-matched unrelated donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI Patients with no history of hematological malignancy and HLA-matched unrelated donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI
    Measure Participants 0 5 1 0
    Count of Participants [Participants]
    5
    Infinity
    1
    20%
    2. Primary Outcome
    Title Incidence of Grades III-IV Acute GVHD
    Description Number of subjects who developed maximum grade acute graft-vs-host disease aGVHD Stages Skin: - a maculopapular eruption involving < 25% BSA - a maculopapular eruption involving 25 - 50% BSA - generalized erythroderma - generalized erythroderma with bullous formation and often with desquamation Liver: - bilirubin 2.0 - 3.0 mg/100 mL - bilirubin 3 - 5.9 mg/100 mL - bilirubin 6 - 14.9 mg/100 mL - bilirubin > 15 mg/100 mL Gut: Diarrhea is graded 1 - 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients with visible bloody diarrhea are at least stage 2 gut and grade 3 overall. aGVHD Grades Grade III: Stage 2 - 4 gastrointestinal involvement and/or +2 to +4 liver involvement, with or without a rash Grade IV: Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death
    Time Frame Up to Day 100

    Outcome Measure Data

    Analysis Population Description
    No subjects meeting the criteria for Arms I or IV were enrolled.
    Arm/Group Title Arm I (2 vs 2.5 vs 3 Gy TBI Dose-escalation) Arm II (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation) Arm III (2 vs 2.5 vs 3 Gy TBI Dose-escalation) Arm IV (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation)
    Arm/Group Description Patients with a history of hematologic malignancy and HLA-haploidentical donor receive fludarabine phosphate (FLU) intravenously (IV) over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF orally (PO) thrice daily (TID) on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI Patients with no history of hematological malignancy and HLA-haploidentical donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI Patients with history of hematologic malignancy and HLA-matched unrelated donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI Patients with no history of hematological malignancy and HLA-matched unrelated donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI
    Measure Participants 0 5 1 0
    Count of Participants [Participants]
    1
    Infinity
    0
    0%
    3. Secondary Outcome
    Title Incidence of Transplant-related Mortality
    Description Number of subjects who expired due to transplant-related mortality
    Time Frame Up to Day 200

    Outcome Measure Data

    Analysis Population Description
    No subjects meeting the criteria for Arms I or IV were enrolled.
    Arm/Group Title Arm I (2 vs 2.5 vs 3 Gy TBI Dose-escalation) Arm II (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation) Arm III (2 vs 2.5 vs 3 Gy TBI Dose-escalation) Arm IV (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation)
    Arm/Group Description Patients with a history of hematologic malignancy and HLA-haploidentical donor receive fludarabine phosphate (FLU) intravenously (IV) over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF orally (PO) thrice daily (TID) on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI Patients with no history of hematological malignancy and HLA-haploidentical donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI Patients with history of hematologic malignancy and HLA-matched unrelated donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI Patients with no history of hematological malignancy and HLA-matched unrelated donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI
    Measure Participants 0 5 1 0
    Count of Participants [Participants]
    1
    Infinity
    0
    0%
    4. Secondary Outcome
    Title Incidence of Adverse Events
    Description Number of subjects who developed reportable AEs, assessed using adapted version of the Common Toxicity Criteria
    Time Frame Up to Day 100

    Outcome Measure Data

    Analysis Population Description
    No subjects meeting the criteria for Arms I or IV were enrolled.
    Arm/Group Title Arm I (2 vs 2.5 vs 3 Gy TBI Dose-escalation) Arm II (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation) Arm III (2 vs 2.5 vs 3 Gy TBI Dose-escalation) Arm IV (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation)
    Arm/Group Description Patients with a history of hematologic malignancy and HLA-haploidentical donor receive fludarabine phosphate (FLU) intravenously (IV) over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF orally (PO) thrice daily (TID) on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI Patients with no history of hematological malignancy and HLA-haploidentical donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI Patients with history of hematologic malignancy and HLA-matched unrelated donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI Patients with no history of hematological malignancy and HLA-matched unrelated donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI
    Measure Participants 0 5 1 0
    Count of Participants [Participants]
    3
    Infinity
    0
    0%

    Adverse Events

    Time Frame AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200
    Adverse Event Reporting Description No subjects meeting the criteria for Arms I or IV were enrolled.
    Arm/Group Title Arm I (2 vs 2.5 vs 3 Gy TBI Dose-escalation) Arm II (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation) Arm III (2 vs 2.5 vs 3 Gy TBI Dose-escalation) Arm IV (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation)
    Arm/Group Description Patients with a history of hematologic malignancy and HLA-haploidentical donor receive fludarabine phosphate (FLU) intravenously (IV) over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF orally (PO) thrice daily (TID) on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI Patients with no history of hematological malignancy and HLA-haploidentical donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI Patients with history of hematologic malignancy and HLA-matched unrelated donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI Patients with no history of hematological malignancy and HLA-matched unrelated donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. Allogeneic Bone Marrow Transplantation: Undergo allogeneic bone marrow transplant Cyclophosphamide: Given IV Cyclosporine: Given IV or PO Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic stem cell transplant Total-Body Irradiation: Undergo TBI
    All Cause Mortality
    Arm I (2 vs 2.5 vs 3 Gy TBI Dose-escalation) Arm II (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation) Arm III (2 vs 2.5 vs 3 Gy TBI Dose-escalation) Arm IV (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/0 (NaN) 2/5 (40%) 0/1 (0%) 0/0 (NaN)
    Serious Adverse Events
    Arm I (2 vs 2.5 vs 3 Gy TBI Dose-escalation) Arm II (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation) Arm III (2 vs 2.5 vs 3 Gy TBI Dose-escalation) Arm IV (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/0 (NaN) 2/5 (40%) 0/1 (0%) 0/0 (NaN)
    Gastrointestinal disorders
    severe abdominal pain associated with GVHD 0/0 (NaN) 0 1/5 (20%) 1 0/1 (0%) 0 0/0 (NaN) 0
    Infections and infestations
    Death 0/0 (NaN) 0 1/5 (20%) 1 0/1 (0%) 0 0/0 (NaN) 0
    Other (Not Including Serious) Adverse Events
    Arm I (2 vs 2.5 vs 3 Gy TBI Dose-escalation) Arm II (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation) Arm III (2 vs 2.5 vs 3 Gy TBI Dose-escalation) Arm IV (2 vs 2.5 vs 3 vs 1 vs 0 Gy TBI De-escalation)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/0 (NaN) 3/5 (60%) 0/1 (0%) 0/0 (NaN)
    Gastrointestinal disorders
    Mucositis 0/0 (NaN) 0 2/5 (40%) 2 0/1 (0%) 0 0/0 (NaN) 0
    diarrhea 0/0 (NaN) 0 1/5 (20%) 1 0/1 (0%) 0 0/0 (NaN) 0
    Hepatobiliary disorders
    elevated bilitrubin 0/0 (NaN) 0 2/5 (40%) 3 0/1 (0%) 0 0/0 (NaN) 0
    Respiratory, thoracic and mediastinal disorders
    pulmonary hemorrage 0/0 (NaN) 0 1/5 (20%) 1 0/1 (0%) 0 0/0 (NaN) 0
    acute respiratory distress syndrome 0/0 (NaN) 0 1/5 (20%) 1 0/1 (0%) 0 0/0 (NaN) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Hans-Peter Kiem
    Organization Fred Hutchinson Cancer Research Center
    Phone 206-667-4425
    Email hkiem@fredhutch.org
    Responsible Party:
    Fred Hutchinson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT00453388
    Other Study ID Numbers:
    • 2064.00
    • NCI-2010-00238
    • 2064.00
    • P30CA015704
    First Posted:
    Mar 28, 2007
    Last Update Posted:
    Jan 29, 2020
    Last Verified:
    Dec 1, 2019