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

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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

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
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.

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

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.

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

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.

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

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.

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


Participant Flow:   Overall Study
    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)
STARTED   0   5   1   0 
COMPLETED   0   5   1   0 
NOT COMPLETED   0   0   0   0 



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
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.

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

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.

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

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.

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

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.

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 Total of all reporting groups

Baseline Measures
   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 
Overall Participants Analyzed 
[Units: Participants]
 0   5   1   0   6 
Age 
[Units: Participants]
Count of 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 
[Units: Years]
Median (Full Range)
    11.1 
 (6.9 to 13.9) 
 11.9 
 (11.9 to 11.9) 
    11.1 
 (6.9 to 13.9) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
         
Female         5 100.0%      0   0.0%         5  83.3% 
Male         0   0.0%      1 100.0%         1  16.7% 
Region of Enrollment 
[Units: Participants]
         
United States      3   1      4 
Brazil      2   0      2 


  Outcome Measures

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

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

3.  Secondary:   Incidence of Transplant-related Mortality   [ Time Frame: Up to Day 200 ]

4.  Secondary:   Incidence of Adverse Events   [ Time Frame: Up to 6 years ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

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
e-mail: hkiem@fredhutch.org



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