ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00453388
Recruitment Status : Active, not recruiting
First Posted : March 28, 2007
Results First Posted : May 24, 2017
Last Update Posted : June 29, 2018
Sponsor:
Collaborators:
National Cancer Institute (NCI)
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Hans-Peter Kiem, Fred Hutchinson Cancer Research Center

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Acute Myeloid Leukemia in Remission
de Novo Myelodysplastic Syndrome
Fanconi Anemia
Previously Treated Myelodysplastic Syndrome
Interventions 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
Enrollment 6
Recruitment Details  
Pre-assignment Details  
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)
Hide 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
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
Hide 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 Number of Baseline Participants 0 5 1 0 6
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants 5 participants 1 participants 0 participants 6 participants
<=18 years
5
 100.0%
1
 100.0%
6
 100.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 0 participants 5 participants 1 participants 0 participants 6 participants
11.1
(6.9 to 13.9)
11.9
(11.9 to 11.9)
11.1
(6.9 to 13.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants 5 participants 1 participants 0 participants 6 participants
Female
5
 100.0%
0
   0.0%
5
  83.3%
Male
0
   0.0%
1
 100.0%
1
  16.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 0 participants 5 participants 1 participants 0 participants 6 participants
United States 3 1 4
Brazil 2 0 2
1.Primary Outcome
Title Number of Patients Who Engraft at Each Dose of TBI Used
Hide Description Number of subjects who engrafted. Engraftment defined as greater than 95% donor chimerism.
Time Frame Up to Day 200
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
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)
Hide 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

Overall Number of Participants Analyzed 0 5 1 0
Measure Type: Count of Participants
Unit of Measure: Participants
5
 100.0%
1
 100.0%
2.Primary Outcome
Title Incidence of Grades III-IV Acute GVHD
Hide Description

Number of subjects who developed maximum grade acute graft-vs-host disease

aGVHD Stages

Skin:

  1. - a maculopapular eruption involving < 25% BSA
  2. - a maculopapular eruption involving 25 - 50% BSA
  3. - generalized erythroderma
  4. - generalized erythroderma with bullous formation and often with desquamation

Liver:

  1. - bilirubin 2.0 - 3.0 mg/100 mL
  2. - bilirubin 3 - 5.9 mg/100 mL
  3. - bilirubin 6 - 14.9 mg/100 mL
  4. - 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
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)
Hide 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

Overall Number of Participants Analyzed 0 5 1 0
Measure Type: Count of Participants
Unit of Measure: Participants
1
  20.0%
0
   0.0%
3.Secondary Outcome
Title Incidence of Transplant-related Mortality
Hide Description Number of subjects who expired due to transplant-related mortality
Time Frame Up to Day 200
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
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)
Hide 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

Overall Number of Participants Analyzed 0 5 1 0
Measure Type: Count of Participants
Unit of Measure: Participants
1
  20.0%
0
   0.0%
4.Secondary Outcome
Title Incidence of Adverse Events
Hide Description Number of subjects who developed reportable AEs, assessed using adapted version of the Common Toxicity Criteria
Time Frame Up to 6 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
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)
Hide 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

Overall Number of Participants Analyzed 0 5 1 0
Measure Type: Count of Participants
Unit of Measure: Participants
3
  60.0%
0
   0.0%
Time Frame AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200
Adverse Event Reporting Description [Not Specified]
 
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)
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/0      2/5 (40.00%)      0/1 (0.00%)      0/0    
Show Serious Adverse Events Hide 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      2/5 (40.00%)      0/1 (0.00%)      0/0    
Gastrointestinal disorders         
severe abdominal pain associated with GVHD   0/0  0 1/5 (20.00%)  1 0/1 (0.00%)  0 0/0  0
Infections and infestations         
Death  [1]  0/0  0 1/5 (20.00%)  1 0/1 (0.00%)  0 0/0  0
Indicates events were collected by systematic assessment
[1]
Septic shock
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
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      3/5 (60.00%)      0/1 (0.00%)      0/0    
Gastrointestinal disorders         
Mucositis   0/0  0 2/5 (40.00%)  2 0/1 (0.00%)  0 0/0 
diarrhea   0/0  0 1/5 (20.00%)  1 0/1 (0.00%)  0 0/0  0
Hepatobiliary disorders         
elevated bilitrubin   0/0  0 2/5 (40.00%)  3 0/1 (0.00%)  0 0/0  0
Respiratory, thoracic and mediastinal disorders         
pulmonary hemorrage   0/0  0 1/5 (20.00%)  1 0/1 (0.00%)  0 0/0  0
acute respiratory distress syndrome   0/0  0 1/5 (20.00%)  1 0/1 (0.00%)  0 0/0  0
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Dr. Hans-Peter Kiem
Organization: Fred Hutchinson Cancer Research Center
Phone: 206-667-4425
Responsible Party: Hans-Peter Kiem, Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT00453388     History of Changes
Other Study ID Numbers: 2064.00
NCI-2010-00238 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2064.00 ( Other Identifier: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium )
P30CA015704 ( U.S. NIH Grant/Contract )
First Submitted: March 27, 2007
First Posted: March 28, 2007
Results First Submitted: April 10, 2017
Results First Posted: May 24, 2017
Last Update Posted: June 29, 2018