- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00968162
Sickle Cell Disease Conditioning for Bone Marrow Transplant
Toward a Less Toxic Yet Highly Effective Conditioning Regimen in Allogeneic Hematopoietic Stem Cell Transplantation for Children and Adolescents With Severe Sickle Cell Disease: A Pilot Study
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Alabama
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Birmingham, Alabama, United States
- University of Alabama-Birmingham
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District of Columbia
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Washington, D.C., District of Columbia, United States
- Children's National Medical Center
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Florida
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Saint Petersburg, Florida, United States, 33701
- All Children's Research Institute Inc.
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Georgia
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Atlanta, Georgia, United States, 30322
- Children's Healthcare of Atlanta
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Louisiana
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New Orleans, Louisiana, United States, 70112
- Tulane University
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Michigan
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Detroit, Michigan, United States, 48202
- Wayne State University
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Mississippi
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Jackson, Mississippi, United States
- University of Mississippi Medical Center
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New York
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The Bronx, New York, United States
- Montefiore Medical Center
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North Carolina
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Chapel Hill, North Carolina, United States, 27516
- University of North Carolina At Chapel Hill
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Texas
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Dallas, Texas, United States
- University of Texas Southwestern
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Up to and including the age of 18 years at time of admission for transplant
- Hemoglobin SS, or hemoglobin S0 thalassemia
- HLA-identical sibling donor (any age) available without HgbSS, SC or S0 thalassemia. As an alternative, HLA identical sibling umbilical cord blood can be used as long as the unit has a pre-cryopreservation TNC dose of greater than 5.0 x 107 TNC/kg recipient weight.
Clinically severe SCD, defined by one of the following:
- Previous clinical stroke, as evidenced by a neurological deficit lasting longer than 24 hours, which is accompanied by radiographic evidence of ischemic brain injury and cerebral vasculopathy.
- Asymptomatic cerebrovascular disease, as evidenced by one the following:
(i)Progressive silent cerebral infarction, as evidenced by serial MRI scans that demonstrate the development of a succession of lesions (at least two temporally discreet lesions, each measuring at least 3 mm in greatest dimension on the most recent scan) or the enlargement of a single lesion, initially measuring at least 3 mm). Lesions must be visible on T2-weighted MRI sequences.
(ii) Cerebral arteriopathy, as evidenced by abnormal TCD testing (confirmed elevated velocities in any single vessel of TAMMV > 200 cm/sec for non-imaging TCD or TAMX > 185 cm/sec for imaging TCD) or by significant vasculopathy on MRA (greater than 50% stenosis of > 2 arterial segments or complete occlusion of any single arterial segment).
(c) Frequent (≥ 3 per year for preceding 2 years) painful vaso-occlusive episodes (defined as episode lasting ≥ 4 hours and requiring hospitalization or outpatient treatment with parenteral opioids). If patient is on hydroxyurea and its use has been associated with a decrease in the frequency of episodes, the frequency should be gauged from the 2 years prior to the start of this drug.
(d) Recurrent (≥ 3 in lifetime) acute chest syndrome events that have necessitated erythrocyte transfusion therapy.
(e) Any combination of ≥ 3 acute chest syndrome episodes and vaso-occlusive pain episodes (defined as above) yearly for 3 years. If patient is on hydroxyurea and its use has been associated with a decrease in the frequency of episodes, the frequency should be gauged from the 3 years prior to the start of this drug.
- Must have been evaluated and adequately counseled regarding treatment options for severe sickle cell disease by a pediatric hematologist.
Exclusion Criteria:
- Biopsy proven chronic active hepatitis, portal fibrosis (greater than score I), or cirrhosis, or serologic evidence of active hepatitis.
- SCD chronic lung disease stage III (see appendix 1).
- Severe renal dysfunction defined as < 50% of predicted normal GFR for age.
- Severe cardiac dysfunction defined as shortening fraction < 25%.
- Severe residual neurologic impairment other than hemiplegia alone, defined as full-scale IQ 70, quadriplegia or paraplegia, inability to ambulate, inability to communicate without assistive device, or any impairment resulting in decline of Lansky performance score to < 70%.
- CNS event occurring within 6 months prior to transplant.
- Karnofsky or Lansky functional performance score < 70%.
- Confirmed HIV seropositivity.
- Patient with unspecified chronic toxicity serious enough to detrimentally affect the patient's capacity to tolerate bone marrow transplantation.
- Patient or patient's guardian(s) unable to understand the nature and risks inherent in the BMT process.
- History of lack of compliance with medical care that would jeopardize transplant course.
- Donor who for psychological, physiologic, or medical reasons is unable to tolerate a bone marrow harvest or receive general anesthesia.
- Donor is HIV infected.
- Donor is pregnant.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Dose de-escalation
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Conduct a pilot trial using a transplant protocol, in which the standard busulfan, cyclophosphamide and anti-thymocyte globulin conditioning regimen is modified by adding fludarabine, a highly immunosuppressive agent, in order to determine the feasibility of reducing the total dose of cyclophosphamide from its present standard of 200 mg/kg to 90 mg/kg and of busulfan from its present standard of 12.8 mg/kg (IV) to 6.4 mg/kg, using a four step dose de-escalation schema.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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Modify the standard dose of busulfan, cyclophosphamide and anti-thymocyte globulin conditioning regimen by adding fludarabine in order to determine the feasibility of reducing the total dose of cyclophosphamide from its present standard of 200 mg/kg.
Time Frame: 1 year after last patient enrolled
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1 year after last patient enrolled
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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To gain insight into the processes that give rise to neurologic problems following bone marrow transplantation and to develop surrogate outcomes.
Time Frame: 1 year after last patient enrolled
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1 year after last patient enrolled
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: John Horan, MD, Emory University
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- IRB00011048
- BMT for SCD (Other Identifier: Other)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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