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Stem Cell Transplant in Sickle Cell Disease and Thalassemia

This study is currently recruiting participants.
Verified July 2017 by Columbia University
Sponsor:
ClinicalTrials.gov Identifier:
NCT00408447
First Posted: December 7, 2006
Last Update Posted: July 14, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Columbia University
  Purpose
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.

Condition Intervention Phase
Sickle Cell Disease Beta Thalassemia Drug: Busulfan Drug: Fludarabine Drug: Alemtuzumab Procedure: Allogeneic stem cell transplant Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Allogeneic Stem Cell Transplant to Induce Mixed Donor Chimerism in Patients With Sickle Cell Disease and Thalassemia

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Prevalence of 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 ]

Secondary Outcome Measures:
  • 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 Beta Thalassemia [ Time Frame: days 60, 100, 180, 365, 730 ]
  • 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 ]
  • 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 ]
  • 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, ]
  • Percent of mixed donor chimerism [ Time Frame: Day +30, 60, 100, 180, 365, 730, and 1005 ]

Estimated Enrollment: 60
Study Start Date: September 2004
Estimated Study Completion Date: November 2017
Estimated Primary Completion Date: November 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
SCD group
Sickle Cell Disease
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
BT group
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

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).
  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Month to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Sickle Cell Disease:

  • Diagnosis of Homozygous Hemoglobin S Disease or Heterozygous Hemoglobin 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.

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00408447


Contacts
Contact: Monica Bhatia, MD 212 305 9138 mb2476@columbia.edu
Contact: Chalitha Robinson, MA 212-305-7213 cr2752@columbia.edu

Locations
United States, New York
Morgan Stanley Children's Hospital, New York-Presbyterian, Columbia University Recruiting
New York, New York, United States, 10032
Contact: Monica Bhatia, MD    212-305-9138    mb2476@columbia.edu   
Principal Investigator: Monica Bhatia, MD         
Sponsors and Collaborators
Columbia University
Investigators
Principal Investigator: Monica Bhatia, MD Columbia University
  More Information

Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Columbia University
ClinicalTrials.gov Identifier: NCT00408447     History of Changes
Other Study ID Numbers: AAAA7701
CHNY-01-503 ( Other Identifier: CU )
First Submitted: December 6, 2006
First Posted: December 7, 2006
Last Update Posted: July 14, 2017
Last Verified: July 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Columbia University:
stem cell transplant
sickle cell disease
thalassemia
moderately ablative
cord blood transplant
matched family donor

Additional relevant MeSH terms:
Thalassemia
beta-Thalassemia
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Fludarabine
Fludarabine phosphate
Alemtuzumab
Busulfan
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Alkylating Agents
Antineoplastic Agents, Alkylating
Myeloablative Agonists