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Trial record 2 of 25 for:    "Thalassemia" | "Busulfan"

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

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.

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

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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
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
Actual Study Start Date : September 2004
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019


Arm Intervention/treatment
SCD group
Sickle Cell Disease patients receiving chemotherapy (Busulfan, Fludarabine and Alemtuzumab) will undergo allogeneic stem cell transplant.
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 patients receiving chemotherapy (Busulfan, Fludarabine and Alemtuzumab) will undergo allogeneic stem cell transplant.
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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. Incidence of primary and secondary graft failure [ Time Frame: Day +42, +60, ]
    To collect data on graft failure

  6. Percent of mixed donor chimerism [ Time Frame: Day +30, 60, 100, 180, 365, 730, and 1005 ]
    To collect data on donor chimerism



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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 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.


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

Locations
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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         
Principal Investigator: Diane George (Acting PI), MD         
Sponsors and Collaborators
Columbia University
Investigators
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Principal Investigator: Monica Bhatia, MD Columbia University

Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Diane George, MD, Assistant Professor of Pediatrics - Acting PI, Columbia University
ClinicalTrials.gov Identifier: NCT00408447     History of Changes
Other Study ID Numbers: AAAA7701
CHNY-01-503 ( Other Identifier: CU )
First Posted: December 7, 2006    Key Record Dates
Last Update Posted: March 14, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Diane George, MD, Columbia University:
stem cell transplant
sickle cell disease
thalassemia
moderately ablative
cord blood transplant
matched family donor
Additional relevant MeSH terms:
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Thalassemia
beta-Thalassemia
Busulfan
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Fludarabine
Fludarabine phosphate
Alemtuzumab
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
Antineoplastic Agents, Immunological