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Stem Cell Transplant in Sickle Cell Disease and Thalassemia

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2011 by Columbia University.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Columbia University
ClinicalTrials.gov Identifier:
NCT00408447
First received: December 6, 2006
Last updated: October 14, 2011
Last verified: October 2011

December 6, 2006
October 14, 2011
December 2001
December 2012   (final data collection date for primary outcome measure)
To determine the toxicity associated with moderately ablative therapy (busulfan/fludarabine/alemtuzumab) and allogeneic stem cell transplantation in selected patients with sickle cell disease and Beta thalassemia [ Time Frame: Day 30, Day 60, Day 100, Day 180, 1 year, 2 years, 3 years, 5 years, 10 years ] [ Designated as safety issue: Yes ]
  • To determine the toxicity associated with moderately ablative therapy (busulfan/fludarabine/alemtuzumab) and allogeneic stem cell transplantation in selected patients with sickle cell disease and Beta thalassemia
  • to determine the incidence of primary and secondary graft failure after moderately ablative therapy and allogeneic stem cell transplantation in selected patient with SCD and BT
  • to determine the percent of mixed donor chimerism following moderately ablative therapy and allogeneic stem cell transplantation in selected patients with SCD and BT. Stable Mixed Chimerism (SMC) is defined as > 50% donor chimerism by day 180.
Complete list of historical versions of study NCT00408447 on ClinicalTrials.gov Archive Site
  • To determine the time to donor hematological reconstitution (neutrophil, RBC and platelet recovery) following moderately ablative therapy and allogeneic stem cell transplantation in selected patients with SCD and BT [ Time Frame: days 30, 60, 100, 180, 365 ] [ Designated as safety issue: No ]
  • to estimate the incidence of acute and chronic graft versus host disease (GVHD) following moderately ablative therapy and allogeneic stem cell transplantation in selected patients with SCD and BT [ Time Frame: as clinically appropriate ] [ Designated as safety issue: No ]
  • to determine the percent of patients who have either a complete, very good partial, partial or no response (clinical/laboratory) following moderately ablative therapy and allogeneic stem cell transplantation in selected patients with SCD and BT [ Time Frame: 6mos, 1 yr, 2 yr ] [ Designated as safety issue: No ]
  • to determine the impact of moderately ablative stem cell transplant on quality of life (QOL) and on neurocognitive functioning of patients with SCD and BT over time. [ Time Frame: Day +180; year 1, 3, 5, 10 ] [ Designated as safety issue: No ]
  • To determine the time to donor hematological reconstitution (neutrophil, RBC and platelet recovery) following moderately ablative therapy and allogeneic stem cell transplantation in selected patients with SCD and BT
  • to estimate the incidence of acute and chronic graft versus host disease (GVHD) following moderately ablative therapy and allogeneic stem cell transplantation in selected patients with SCD and BT
  • to determine the percent of patients who have either a complete, very good partial, partial or no response (clinical/laboratory) following moderately ablative therapy and allogeneic stem cell transplantation in selected patients with SCD and BT
  • to determine the impact of moderately ablative stem cell transplant on quality of life (QOL) and on neurocognitive functioning of patients with SCD and BT over time.
Not Provided
Not Provided
 
Stem Cell Transplant in Sickle Cell Disease and Thalassemia
Allogeneic Stem Cell Transplant to Induce Mixed Donor Chimerism in Patients With Sickle Cell Disease and Thalassemia

Sickle cell disease is a genetic disorder in which a mutation in the beta chain of human hemoglobin results in abnormal blood hemoglobin, causing red blood cells to sickle under stress with resulting symptoms including severe pains and strokes. Beta thalassemia is another genetic disorder in which there are abnormal beta hemoglobin chains, causing anemia. In both disorders, frequent red blood cell transfusions may be required to sustain life, but these often result in complications including multiple hospitalizations, iron overload, or bacterial or viral infections such as hepatitis. Standard drugs and therapies used in the treatment of sickle cell disease and/or beta thalassemia provide only supportive care, and may result in long-term side effects, and inadequate control of the disease process. Bone marrow transplant has been increasingly used for the long-term treatment and cure of sickle cell disease and beta thalassemia. Although, not without acute and potential long term side effects, this alternative offers long term control and potential cure of the disease. Most of the side effects seen with bone marrow transplant are directly related to the high intensity of chemotherapy used (ablative).

The primary purpose of this study is to see if giving lower doses of chemotherapy (moderately ablative) will result in successful bone marrow replacement without as severe side-effects but with permanent control of the disease. Patients will receive a chemotherapy regimen with busulfan, fludarabine, and alemtuzumab followed by an infusion of stem cells, either from a family-related or cord-blood matched donor.

Further study details will be provided by Columbia University, Division of Pediatric Blood & Marrow Transplantation.

STUDY DESIGN:

Patients will receive busulfan, fludarabine and alemtuzumab prior to the stem cell transplant to help the stem cells take and grow. The stem cells will be infused on day 0 through an intravenous catheter. Patients will receive immunosuppressive therapy such as tacrolimus and MMF to prevent graft-versus-disease.

Patients will be followed up after transplant to look for special cells in the blood that show that the new bone marrow is taking hold (engrafting). Response shall be documented at 6 months, 1 year, 2 years and 3 years post-SCT.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Sickle Cell Disease
  • Beta Thalassemia
  • Drug: Busulfan
    Busulfan 4 mg/kg/d x 4d
    Other Name: Busulfex
  • Drug: Fludarabine
    Fludarabine 30 mg/m2/d x 6d
    Other Name: Fludara
  • Drug: Alemtuzumab
    Alemtuzumab 2mg/m2 x 1d, 6mg/m2 x 2 d, 20mg/m2 x 2d
    Other Name: Campath
  • Procedure: Allogeneic stem cell transplant
    Allogeneic stem cells will be given on day 0 (after chemotherapy conditioning)obtained either from a family donor (first degree relative) or sibling cord blood donor.
    Other Names:
    • Related Bone Marrow
    • Related Cord Blood
  • SCD group
    Sickle Cell Disease
    Interventions:
    • Drug: Busulfan
    • Drug: Fludarabine
    • Drug: Alemtuzumab
    • Procedure: Allogeneic stem cell transplant
  • BT group
    Beta Thalassemia
    Interventions:
    • Drug: Busulfan
    • Drug: Fludarabine
    • Drug: Alemtuzumab
    • Procedure: Allogeneic stem cell transplant

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
60
January 2014
December 2012   (final data collection date for primary outcome measure)

Inclusion Criteria

Sickle Cell Disease:

  • Diagnosis of Homozygous Hemoglobin S Disease or Heterozygous Hemoglobin SC or SB/+ thalassemia, or Sickle/variant resulting in Chronic Hemolytic Anemia with HgB < 10 or equal to 10 mg/dL
  • Age < or equal to 21
  • Matched sibling donor and asymptomatic

Thalassemia:

Homozygous B-thalassemia

Clinical syndrome of B-thalassemia intermedia (including double heterozygotes, e.g. Hgb E-Beta thalassemia) who either:

  • Require regular transfusions, or
  • Have evidence of severe ineffective erythropoiesis - marked marrow hyperplasia and the resultant cosmetic abnormalities and/or retardation of growth and development as a result of severe anemia.

and:

  • Lucarelli Stage 1 or 2
  • Age < or equal to 21

Additionally,

Patient must have adequate organ function as below:

  • Adequate renal function defined as serum creatinine < or equal to 1.5 x normal, or creatinine clearance or radioisotope GFR =40 ml/min/m2 or >60 ml/min/1.73 m2 or an equivalent GFR as determined by the institutional normal range.
  • Adequate liver function defined as SGOT (AST) or SGPT (ALT) < 5.0 x normal
  • Adequate cardiac function defined as shortening fraction of ≥28% by echocardiogram, or ejection fraction of ≥48% by radionuclide angiogram or echocardiogram
  • Adequate pulmonary function defined as uncorrected DLCO≥35% by pulmonary function test; for children who are uncooperative, no evidence of dyspnea at rest

Exclusion Criteria

  • Karnofsky/Lansky Performance Score <60%
  • Demonstrated lack of compliance with medical care
  • Pregnant or nursing
  • Sickle Cell Disease: Grade III-IV* residual non-motor neurologic; Grade IV* Hematuria
  • Thalassemia: Lucarelli Stage 3
Both
1 Month to 21 Years
No
Contact: Monica Bhatia, MD 212 305 9138 mb2476@columbia.edu
United States
 
NCT00408447
AAAA7701, CHNY-01-503
Yes
Columbia University
Columbia University
Not Provided
Not Provided
Columbia University
October 2011

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