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Allogeneic Bone Marrow Transplantation for the Treatment of Genetic Disorders of Erythropoiesis

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ClinicalTrials.gov Identifier: NCT00578435
Recruitment Status : Completed
First Posted : December 21, 2007
Last Update Posted : September 12, 2008
Sponsor:
Information provided by:
Memorial Sloan Kettering Cancer Center

Tracking Information
First Submitted Date  ICMJE December 18, 2007
First Posted Date  ICMJE December 21, 2007
Last Update Posted Date September 12, 2008
Study Start Date  ICMJE January 1994
Actual Primary Completion Date August 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 20, 2007)
Define the role of bone marrow transplantation for the treatment of sickle cell disease and the reversibility of sickle cell vasculopathy and organ damage, good risk thalassemia major and Diamond-Blackfan Anemia. [ Time Frame: 2 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Allogeneic Bone Marrow Transplantation for the Treatment of Genetic Disorders of Erythropoiesis
Official Title  ICMJE Allogeneic Bone Marrow Transplantation for the Treatment of Genetic Disorders of Erythropoiesis
Brief Summary The purpose of this study is to determine and confirm the role of bone marrow transplantation in the treatment of disorders of the red cell and hemoglobin including sickle cell anemia, thalassemia and diamond blackfan anemia.
Detailed Description

The trial proposed is a single armed phase II treatment protocol designed to examine the engraftment,toxicity and graft-versus-host disease following a novel cytoreductive regimen including cyclophosphamide and Busulfan for the treatment of patients with Severe Sickle Cell Anemia,Thalassemia, and Diamond Blackfan Anemia using stem cell transplants derived from HLA-genotypically identical siblings.

Patients will be conditioned for transplantation with cyclophosphamide (50 mg/kg/day x 4 days), and busulfan [(if < 4 years of age 1 mg/kg 4 times per day x 4 days), (if > 4 years of age 0.8 mg/kg 4 times per day x 4 days)]. Patients will receive Methotrexate & Cyclosporin-A for prophylaxis against GvHD and GCSF to promote engraftment.

The preferred source of stem cells from related HLA-matched related donors will be unmodified bone marrow stem cells.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Genetic Disorders
  • Sickle Cell Anemia
Intervention  ICMJE Procedure: Busulfan, Cyclophosphamide, BMD
Busulfan 0.8 or 1 mg/Kg/day Days 8-6 Cyclophosphamide 50 mg/Kg/day Days 2-5 BMT Day 0
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Estimated Enrollment  ICMJE
 (submitted: December 20, 2007)
25
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE August 2008
Actual Primary Completion Date August 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients with severe HOMOZYGOUS SICKLE CELL ANEMIA or SICKLE/BETA THALASSEMIA
  • Neurologic event (stroke or hemorrhage).
  • Abnormal cerebral MRI scan and cerebral arteriogram or MRI angiographic study (MRA) and impaired neuropsychologic testing.
  • Recurrent acute chest syndrome (> 2 episodes)
  • Stage I-II sickle chronic lung disease
  • Sickle cell nephropathy (moderate or severe proteinuria or GFR 30-50% of predicted for age.
  • Major visual impairment in at least one eye with bilateral proliferative retinopathy.
  • Osteonecrosis of multiple bones
  • Chronic debilitating pain secondary to vasoocclusive crisis (>= 3 episodes per year for >= 3 years) Recurrent priapism
  • Allo-immunization with the development of antibodies following chronic transfusion therapy
  • Patients with HOMOZYGOUS SICKLE CELL ANEMIA or SICKLE/BETA THALASSEMIA with the following criteria will be considered for accrual on this protocol
  • Patients < 2 years with high WBC counts and/or >1 episode of dactylitis and/or a Hgb < 7 g/dl
  • History of death from sickle cell disease in sibship of patient
  • Patients with BETA-THALASSEMIA MAJOR with Lucarelli class 1 or 2 risk status i.e with only 0-2 of the following factors: hepatomegaly, portal fibrosis, or poor chelation therapy
  • Patients with DIAMOND-BLACKFAN ANEMIA who have failed conventional therapy.
  • Patients must have an HLA-compatible related donor. The donor must be healthy and able to undergo general anesthesia. Donors with heterozygous sickle cell anemia (hemoglobin AS) or with heterozygous thalassemia are acceptable donors.
  • At the time of referral for transplantation, patients must be in good clinical condition without any evidence of infections and a Karnofsky or Lansky pediatric performance scale > 70%
  • Each patient and donor must be willing to participate as a research subject and must sign an informed consent form after having been advised as to the nature and risk of the study prior to entering the protocol. Parents or legal guardians of patients who are minor will sign the consent form after being advised of the nature and risks of the study

Exclusion Criteria:

  • Patients whose life expectancy is less than 8 weeks. Patients with a Karnofsky or Lansky performance score of < 70%
  • Patients with severe major organ dysfunction:
  • Patients with severe renal impairment. This will be determined by a creatinine clearance < 70 ml/min/1.73 m2 (or serum creatinine > 1.5 x Normal) or by a glomerular filtration rate < 30% of predicted normal for age
  • Inadequate cardiac function as determined by fractional shortening < 28% on echocardiogram, and/or ejection fraction of < 50% on echocardiogram or RNCA.
  • Patients with FS of 23-28% who show an increase in FS in response to stress on the supine bicycle ergometer are eligible
  • Major liver dysfunction: SGOT > 3 x upper limit of normal. Hyperbilirubinemia will not be used as an exclusion criteria because of the hemolytic component of the bilirubin. Patients with active hepatitis or severe liver fibrosis will also be excluded
  • Severe residual functional neurologic impairment
  • Stage III-IV sickle chronic lung disease
  • Pregnant or lactating women are excluded
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00578435
Other Study ID Numbers  ICMJE 94-005
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Fourid Boulad, Memorial Sloan-Kettering Cancer Center
Study Sponsor  ICMJE Memorial Sloan Kettering Cancer Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Farid Boulad, MD Memorial Sloan Kettering Cancer Center
PRS Account Memorial Sloan Kettering Cancer Center
Verification Date September 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP