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Hematopoietic Stem Cell Transplantation for the Treatment of Patients With Fanconi Anemia Lacking a Genotypically Identical Donor, Using a Chemotherapy Only Cytoreduction With Busulfan, Cyclophosphamide and Fludarabine

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ClinicalTrials.gov Identifier: NCT00987480
Recruitment Status : Completed
First Posted : October 1, 2009
Results First Posted : July 10, 2018
Last Update Posted : July 10, 2018
Sponsor:
Collaborators:
Boston Children’s Hospital
Children's Hospital Medical Center, Cincinnati
Children's Hospital and Health System Foundation, Wisconsin
Rockefeller University
Fred Hutchinson Cancer Research Center
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Aplastic Anemia
Leukemia
Myelodysplastic Syndrome
Interventions Drug: Busulfan, fludarabine, & cyclophosphamide with immunosuppression with ATG and cyclosporine.
Device: CliniMACS device
Enrollment 45
Recruitment Details  
Pre-assignment Details

This is a multicenter site and MSK is the site responsible for data collection and analysis for all sites.

11 participants were enrolled at Memorial Sloan Kettering Cancer Center. The remaining 34 participants were enrolled at the participating institutions. This makes a total of 45 participants enrolled and treated on this study.

Arm/Group Title Chemotherapy-based Cytoreductive Regimen Plus a CD34+ Selected
Hide Arm/Group Description

This phase II trial is designed to investigate the safety and efficacy of a chemotherapy-based cytoreductive regimen plus a CD34+ selected T-cell depleted peripheral blood stem cell (PBSC) stem cell transplant for the treatment of patients with Fanconi anemia and severe hematologic disease.

Busulfan, fludarabine, & cyclophosphamide with immunosuppression with ATG and cyclosporine.: There are three parts in this transplant study. 1) There will be a pre-transplant - preparation - period to see if patient qualifies for the transplant study. This will be done as an outpatient and lasts 2-4 weeks. Once this is completed, there will be 2) the transplant period itself, during which the patient will be admitted and will be an inpatient. This period usually last for 4-6 weeks. Following that, there will be a 3) post transplant period, during which the patient will be watched carefully and monitored in clinic as an out patient. The post transplant period lasts from three months to one year.

Period Title: Overall Study
Started 45
Completed 45
Not Completed 0
Arm/Group Title Chemotherapy-based Cytoreductive Regimen Plus a CD34+ Selected
Hide Arm/Group Description

This phase II trial is designed to investigate the safety and efficacy of a chemotherapy-based cytoreductive regimen plus a CD34+ selected T-cell depleted peripheral blood stem cell (PBSC) stem cell transplant for the treatment of patients with Fanconi anemia and severe hematologic disease.

Busulfan, fludarabine, & cyclophosphamide with immunosuppression with ATG and cyclosporine.: There are three parts in this transplant study. 1) There will be a pre-transplant - preparation - period to see if patient qualifies for the transplant study. This will be done as an outpatient and lasts 2-4 weeks. Once this is completed, there will be 2) the transplant period itself, during which the patient will be admitted and will be an inpatient. This period usually last for 4-6 weeks. Following that, there will be a 3) post transplant period, during which the patient will be watched carefully and monitored in clinic as an out patient. The post transplant period lasts from three months to one year.

Overall Number of Baseline Participants 45
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 45 participants
8.2
(4.3 to 44)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 45 participants
Female
25
  55.6%
Male
20
  44.4%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 45 participants
Hispanic or Latino
5
  11.1%
Not Hispanic or Latino
0
   0.0%
Unknown or Not Reported
40
  88.9%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 45 participants
American Indian or Alaska Native
0
   0.0%
Asian
2
   4.4%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
3
   6.7%
White
36
  80.0%
More than one race
0
   0.0%
Unknown or Not Reported
4
   8.9%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 45 participants
45
 100.0%
1.Primary Outcome
Title Successful Neutrophil Engraftment
Hide Description [Not Specified]
Time Frame 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Chemotherapy-based Cytoreductive Regimen Plus a CD34+ Selected
Hide Arm/Group Description:

This phase II trial is designed to investigate the safety and efficacy of a chemotherapy-based cytoreductive regimen plus a CD34+ selected T-cell depleted peripheral blood stem cell (PBSC) stem cell transplant for the treatment of patients with Fanconi anemia and severe hematologic disease.

Busulfan, fludarabine, & cyclophosphamide with immunosuppression with ATG and cyclosporine.: There are three parts in this transplant study. 1) There will be a pre-transplant - preparation - period to see if patient qualifies for the transplant study. This will be done as an outpatient and lasts 2-4 weeks. Once this is completed, there will be 2) the transplant period itself, during which the patient will be admitted and will be an inpatient. This period usually last for 4-6 weeks. Following that, there will be a 3) post transplant period, during which the patient will be watched carefully and monitored in clinic as an out patient. The post transplant period lasts from three months to one year.

Overall Number of Participants Analyzed 45
Measure Type: Count of Participants
Unit of Measure: Participants
Achieved neutrophil engraftment
44
  97.8%
Did not achieve neutrophil engraftment
1
   2.2%
2.Primary Outcome
Title The Incidence of Early Transplant Related Mortality
Hide Description [Not Specified]
Time Frame 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Chemotherapy-based Cytoreductive Regimen Plus a CD34+ Selected
Hide Arm/Group Description:

This phase II trial is designed to investigate the safety and efficacy of a chemotherapy-based cytoreductive regimen plus a CD34+ selected T-cell depleted peripheral blood stem cell (PBSC) stem cell transplant for the treatment of patients with Fanconi anemia and severe hematologic disease.

Busulfan, fludarabine, & cyclophosphamide with immunosuppression with ATG and cyclosporine.: There are three parts in this transplant study. 1) There will be a pre-transplant - preparation - period to see if patient qualifies for the transplant study. This will be done as an outpatient and lasts 2-4 weeks. Once this is completed, there will be 2) the transplant period itself, during which the patient will be admitted and will be an inpatient. This period usually last for 4-6 weeks. Following that, there will be a 3) post transplant period, during which the patient will be watched carefully and monitored in clinic as an out patient. The post transplant period lasts from three months to one year.

Overall Number of Participants Analyzed 45
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
3.Primary Outcome
Title The Incidence of Acute GvHD
Hide Description [Not Specified]
Time Frame 100 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Chemotherapy-based Cytoreductive Regimen Plus a CD34+ Selected
Hide Arm/Group Description:

This phase II trial is designed to investigate the safety and efficacy of a chemotherapy-based cytoreductive regimen plus a CD34+ selected T-cell depleted peripheral blood stem cell (PBSC) stem cell transplant for the treatment of patients with Fanconi anemia and severe hematologic disease.

Busulfan, fludarabine, & cyclophosphamide with immunosuppression with ATG and cyclosporine.: There are three parts in this transplant study. 1) There will be a pre-transplant - preparation - period to see if patient qualifies for the transplant study. This will be done as an outpatient and lasts 2-4 weeks. Once this is completed, there will be 2) the transplant period itself, during which the patient will be admitted and will be an inpatient. This period usually last for 4-6 weeks. Following that, there will be a 3) post transplant period, during which the patient will be watched carefully and monitored in clinic as an out patient. The post transplant period lasts from three months to one year.

Overall Number of Participants Analyzed 45
Measure Type: Number
Unit of Measure: percentage of participants
6.7
4.Primary Outcome
Title The Incidence of Chronic GvHD
Hide Description [Not Specified]
Time Frame 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Chemotherapy-based Cytoreductive Regimen Plus a CD34+ Selected
Hide Arm/Group Description:

This phase II trial is designed to investigate the safety and efficacy of a chemotherapy-based cytoreductive regimen plus a CD34+ selected T-cell depleted peripheral blood stem cell (PBSC) stem cell transplant for the treatment of patients with Fanconi anemia and severe hematologic disease.

Busulfan, fludarabine, & cyclophosphamide with immunosuppression with ATG and cyclosporine.: There are three parts in this transplant study. 1) There will be a pre-transplant - preparation - period to see if patient qualifies for the transplant study. This will be done as an outpatient and lasts 2-4 weeks. Once this is completed, there will be 2) the transplant period itself, during which the patient will be admitted and will be an inpatient. This period usually last for 4-6 weeks. Following that, there will be a 3) post transplant period, during which the patient will be watched carefully and monitored in clinic as an out patient. The post transplant period lasts from three months to one year.

Overall Number of Participants Analyzed 45
Measure Type: Count of Participants
Unit of Measure: Participants
Developed limited chronic GVHD
3
   6.7%
Did not develop limited chronic GVHD
42
  93.3%
5.Secondary Outcome
Title Overall Survival at 3 Years
Hide Description Overall Survival is defined as time from date of transplant to event (death from any cause) or last follow-up.
Time Frame 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Chemotherapy-based Cytoreductive Regimen Plus a CD34+ Selected
Hide Arm/Group Description:

This phase II trial is designed to investigate the safety and efficacy of a chemotherapy-based cytoreductive regimen plus a CD34+ selected T-cell depleted peripheral blood stem cell (PBSC) stem cell transplant for the treatment of patients with Fanconi anemia and severe hematologic disease.

Busulfan, fludarabine, & cyclophosphamide with immunosuppression with ATG and cyclosporine.: There are three parts in this transplant study. 1) There will be a pre-transplant - preparation - period to see if patient qualifies for the transplant study. This will be done as an outpatient and lasts 2-4 weeks. Once this is completed, there will be 2) the transplant period itself, during which the patient will be admitted and will be an inpatient. This period usually last for 4-6 weeks. Following that, there will be a 3) post transplant period, during which the patient will be watched carefully and monitored in clinic as an out patient. The post transplant period lasts from three months to one year.

Overall Number of Participants Analyzed 45
Measure Type: Number
Unit of Measure: percentage of participants
80
6.Secondary Outcome
Title Disease-free Survival at 3 Years
Hide Description

Defined as time from date of transplant to relapse, graft rejection or graft failure, or death.

Primary non-engraftment is diagnosed when the participants fails to achieve an ANC >/= 500/ul at any time in the first 28 days post-transplant.

For participants with MDS or AML, relapse will be analyzed as to type and genetic origin of the MDS/leukemic cells. These will be defined by an increasing number of blasts in the marrow over 5% by the presence of circulating peripheral blasts, or by the presence of blasts in any extramedullary site. Cytogenetic analysis of the marrow and/or peripheral blood will also be obtained for the diagnosis of relapse.

Time Frame 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Chemotherapy-based Cytoreductive Regimen Plus a CD34+ Selected
Hide Arm/Group Description:

This phase II trial is designed to investigate the safety and efficacy of a chemotherapy-based cytoreductive regimen plus a CD34+ selected T-cell depleted peripheral blood stem cell (PBSC) stem cell transplant for the treatment of patients with Fanconi anemia and severe hematologic disease.

Busulfan, fludarabine, & cyclophosphamide with immunosuppression with ATG and cyclosporine.: There are three parts in this transplant study. 1) There will be a pre-transplant - preparation - period to see if patient qualifies for the transplant study. This will be done as an outpatient and lasts 2-4 weeks. Once this is completed, there will be 2) the transplant period itself, during which the patient will be admitted and will be an inpatient. This period usually last for 4-6 weeks. Following that, there will be a 3) post transplant period, during which the patient will be watched carefully and monitored in clinic as an out patient. The post transplant period lasts from three months to one year.

Overall Number of Participants Analyzed 45
Measure Type: Number
Unit of Measure: percentage of participants
77.8
Time Frame 1 year
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Chemotherapy-based Cytoreductive Regimen Plus a CD34+ Selected
Hide Arm/Group Description This phase II trial is designed to investigate the safety and efficacy of a chemotherapy-based cytoreductive regimen plus a CD34+ selected T-cell depleted peripheral blood stem cell (PBSC) stem cell transplant for the treatment of patients with Fanconi anemia and severe hematologic disease
All-Cause Mortality
Chemotherapy-based Cytoreductive Regimen Plus a CD34+ Selected
Affected / at Risk (%)
Total   9/45 (20.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Chemotherapy-based Cytoreductive Regimen Plus a CD34+ Selected
Affected / at Risk (%)
Total   11/45 (24.44%) 
Blood and lymphatic system disorders   
Blood/Bone Marrow, Other   1/45 (2.22%) 
Cardiac disorders   
Cardiopulmonary arrest, cause unknkown   1/45 (2.22%) 
Gastrointestinal disorders   
Gastrointestinal, other   1/45 (2.22%) 
Hemorrhage, Oral cavity   1/45 (2.22%) 
Hemorrhage, Stoma (GI)   1/45 (2.22%) 
Ileus, GI (func obstruction of bowel)   1/45 (2.22%) 
Mucositis (Clin exam)- Oral cavity   1/45 (2.22%) 
General disorders   
Death NOS   3/45 (6.67%) 
Infections and infestations   
Inf norm ANC/gr1/2 neut-Blood   1/45 (2.22%) 
Inf norm ANC/gr1/2 neut-Meningitis(meninges)   1/45 (2.22%) 
Inf norm ANC/gr1/2 neut-Myositis infection(muscle)   1/45 (2.22%) 
Infection w/ Gr 3/4 neut, Blood   1/45 (2.22%) 
Infection, other   4/45 (8.89%) 
Investigations   
Bilirubin (hyperbilirubinemia)   1/45 (2.22%) 
Nervous system disorders   
Neurology - Other (specify)   1/45 (2.22%) 
Neuropathy: motor   1/45 (2.22%) 
Seizure   1/45 (2.22%) 
Psychiatric disorders   
Confusion   1/45 (2.22%) 
Respiratory, thoracic and mediastinal disorders   
Dyspnea   1/45 (2.22%) 
Hemorrhage, Respiratory tract NOS   1/45 (2.22%) 
Hypoxia   7/45 (15.56%) 
Pneumonitis/pulm infiltrates   2/45 (4.44%) 
Pulm/upp respiratory - Other (spec)   1/45 (2.22%) 
Pulmonary hypertension   1/45 (2.22%) 
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Chemotherapy-based Cytoreductive Regimen Plus a CD34+ Selected
Affected / at Risk (%)
Total   31/45 (68.89%) 
Blood and lymphatic system disorders   
Lymphopenia   8/45 (17.78%) 
Gastrointestinal disorders   
Mucositis (Clin exam)- Pharynx   4/45 (8.89%) 
Mucositis (Clin exam)- Oral cavity   15/45 (33.33%) 
Infections and infestations   
Infection, other   5/45 (11.11%) 
Investigations   
Aspartate aminotransferase increased   3/45 (6.67%) 
Bicarbonate, serum-low   3/45 (6.67%) 
Blood bilirubin increased   3/45 (6.67%) 
Alanine aminotransferase increased   5/45 (11.11%) 
INR   6/45 (13.33%) 
Alkaline phosphatase   7/45 (15.56%) 
PTT   7/45 (15.56%) 
Creatinine   8/45 (17.78%) 
Hemoglobin   8/45 (17.78%) 
Leukocytes (total WBC)   8/45 (17.78%) 
Neutrophils/granulocytes (ANC/AGC)   8/45 (17.78%) 
Platelets   8/45 (17.78%) 
AST, SGOT   10/45 (22.22%) 
ALT, SGPT   11/45 (24.44%) 
Bilirubin (hyperbilirubinemia)   11/45 (24.44%) 
Metabolism and nutrition disorders   
Sodium, high (hypernatremia)   3/45 (6.67%) 
Glucose, low (hypoglycemia)   4/45 (8.89%) 
Hypermagnesemia   4/45 (8.89%) 
Phosphate, low (hypophosphatemia)   4/45 (8.89%) 
Hyperglycemia   6/45 (13.33%) 
Magnesium, high (hypermagnesemia)   6/45 (13.33%) 
Magnesium, low (hypomagnesemia)   6/45 (13.33%) 
Trglycrde, high (hypertriglyceridemia)   6/45 (13.33%) 
Potassium, high (hyperkalemia)   7/45 (15.56%) 
Albumin, low (hypoalbuminemia)   8/45 (17.78%) 
Sodium, low (hyponatremia)   9/45 (20.00%) 
Potassium, low (hypokalemia)   10/45 (22.22%) 
Glucose, high (hyperglycemia)   14/45 (31.11%) 
Vascular disorders   
Hypertension   8/45 (17.78%) 
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. Farid Boulad
Organization: Memorial Sloan Kettering Cancer Center
Phone: 212-639-2429
Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00987480     History of Changes
Obsolete Identifiers: NCT00850317
Other Study ID Numbers: 08-031
First Submitted: September 30, 2009
First Posted: October 1, 2009
Results First Submitted: March 2, 2018
Results First Posted: July 10, 2018
Last Update Posted: July 10, 2018