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Stem Cell Transplant in Sickle Cell Disease and Thalassemia

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ClinicalTrials.gov Identifier: NCT00408447
Recruitment Status : Recruiting
First Posted : December 7, 2006
Last Update Posted : March 14, 2019
Sponsor:
Information provided by (Responsible Party):
Diane George, MD, Columbia University

Tracking Information
First Submitted Date  ICMJE December 6, 2006
First Posted Date  ICMJE December 7, 2006
Last Update Posted Date March 14, 2019
Actual Study Start Date  ICMJE September 2004
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 12, 2019)
Prevalence of toxicity associated with moderately ablative therapy (busulfan/fludarabine/alemtuzumab) and allogeneic stem cell transplantation in selected patients with Sickle Cell Disease (SCD) and Beta Thalassemia (BT) [ Time Frame: Day 30, Day 60, Day 100, Day 180, 1 year, 2 years, 3 years, 5 years, 10 years ]
To examine if giving lower doses of chemotherapy will result in less severe side-effects but with permanent control of the disease.
Original Primary Outcome Measures  ICMJE
 (submitted: December 6, 2006)
  • 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.
Change History Complete list of historical versions of study NCT00408447 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 12, 2019)
  • Time to donor hematological reconstitution (neutrophil, red blood cell and platelet recovery) following moderately ablative therapy and allogeneic stem cell transplantation in selected patients with SCD and BT [ Time Frame: days 60, 100, 180, 365, 730 ]
    To examine if giving lower doses of chemotherapy and bone marrow replacement can result in control of the disease.
  • 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 ]
    To examine if giving lower doses of chemotherapy will result in successful bone marrow replacement.
  • 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 ]
    To examine if giving lower doses of chemotherapy with bone marrow replacement will result in good control of the disease.
  • Quality of life (QOL) score [ Time Frame: Day +180; year 1, 3, 5, 10 ]
    To determine the impact of moderately ablative stem cell transplant on quality of life and neurocognitive functioning with SCD over time
  • Incidence of primary and secondary graft failure [ Time Frame: Day +42, +60, ]
    To collect data on graft failure
  • Percent of mixed donor chimerism [ Time Frame: Day +30, 60, 100, 180, 365, 730, and 1005 ]
    To collect data on donor chimerism
Original Secondary Outcome Measures  ICMJE
 (submitted: December 6, 2006)
  • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Stem Cell Transplant in Sickle Cell Disease and Thalassemia
Official Title  ICMJE Allogeneic Stem Cell Transplant to Induce Mixed Donor Chimerism in Patients With Sickle Cell Disease and Thalassemia
Brief Summary 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.
Detailed Description 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).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Sickle Cell Disease
  • Beta Thalassemia
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • SCD group
    Sickle Cell Disease patients receiving chemotherapy (Busulfan, Fludarabine and Alemtuzumab) will undergo allogeneic stem cell transplant.
    Interventions:
    • Drug: Busulfan
    • Drug: Fludarabine
    • Drug: Alemtuzumab
    • Procedure: Allogeneic stem cell transplant
  • BT group
    Beta Thalassemia patients receiving chemotherapy (Busulfan, Fludarabine and Alemtuzumab) will undergo allogeneic stem cell transplant.
    Interventions:
    • Drug: Busulfan
    • Drug: Fludarabine
    • Drug: Alemtuzumab
    • Procedure: Allogeneic stem cell transplant
Publications *

*   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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 6, 2006)
60
Original Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2019
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Sickle Cell Disease:

  • Diagnosis of Homozygous Hemoglobin S Disease or Heterozygous Hemoglobin Sickle Cell (SC) or S 0/+ thalassemia, or Sickle/variant resulting in Chronic Hemolytic Anemia with hemoglobin (HgB) ≤10 mg/dL
  • Age ≤30
  • Matched sibling donor and asymptomatic, or 8/8 human leukocyte antigen (HLA) matched unrelated adult donor

Patient must have adequate organ function as below:

  • Adequate renal function defined as serum creatinine ≤1.5 x normal, or Creatinine clearance or radioisotope glomerular filtration rate (GFR) >100 ml/min/1.73 m2 or >70ml/min/1.73m2 for patients >16 years old
  • Adequate liver function defined as serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase (AST)) or serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase (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 corrected Diffusing capacity of the lungs for carbon monoxide (DLCO) ≥40% by pulmonary function test, or for children who are unable to perform DLCO maneuver ≥85% O2 saturation, no evidence of dyspnea at rest

Exclusion criteria:

General

  • Karnofsky/Lansky Performance Score <60%
  • Demonstrated lack of compliance with medical care
  • Pregnant or nursing
  • Evidence of uncontrolled bacterial, viral or fungal infections (currently taking medication and progression of clinical symptoms) within 1 month prior to starting the conditioning regimen. Patients with fever or suspected minor infection should await resolution of symptoms before starting the conditioning regimen.

Histologic Exam of Liver (liver biopsy) with bridging fibrosis or cirrhosis.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Month to 30 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Monica Bhatia, MD 212 305 9138 mb2476@columbia.edu
Contact: Chalitha Robinson, MA 212-305-7213 cr2752@columbia.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00408447
Other Study ID Numbers  ICMJE AAAA7701
CHNY-01-503 ( Other Identifier: CU )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Diane George, MD, Columbia University
Study Sponsor  ICMJE Columbia University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Monica Bhatia, MD Columbia University
PRS Account Columbia University
Verification Date March 2019

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