Beta Thalassemia, Sickle Cell Disease
Conditions
Keywords
stem cell transplant, sickle cell disease, thalassemia, moderately ablative, cord blood transplant, matched family donor
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).
Interventions
DRUGBusulfan
Busulfan 4 mg/kg/d x 4d
DRUGFludarabine
Fludarabine 30 mg/m2/d x 6d
DRUGAlemtuzumab
Alemtuzumab 2mg/m2 x 1d, 6mg/m2 x 2 d, 20mg/m2 x 2d
PROCEDUREAllogeneic 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.
Sponsors
Columbia University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Months to 30 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 | 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. |
| 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 | 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 primary and secondary graft failure | Day +42, +60, | To collect data on graft failure |
| Percent of mixed donor chimerism | Day +30, 60, 100, 180, 365, 730, and 1005 | To collect data on donor chimerism |
| Quality of life (QOL) score | 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 |
Countries
United States
Outcome results
None listed