HSCT For Patients With High Risk Hemoglobinopathies Using Reduced Intensity

• Status: Completed
• Trial end date: 2019-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This study will evaluate the use of reduced intensity conditioning regimen in patients with high risk hemoglobinopathy Sickle Cell and B-Thalassemia Major in combination with standard immunosuppressive medications, followed by a routine stem cell transplant in order to assess whether or not it is as effective as myeloablative high dose chemotherapy and transplant.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Northwell Health
• Treatments: Alemtuzumab; Cyclosporine; Cyclosporins; Fludarabine; Fludarabine phosphate; Melphalan; Mycophenolate mofetil; Mycophenolic Acid; Tacrolimus

Criteria

Inclusion Criteria:

• Patient Inclusion Criteria for Sickle Cell Disease

• Patients at least one year of age to less than or equal to 21 years of age with (Sickle Cell Disease-SS or Sickle Cell-S-β-Thalassemia and with one or more of the following disease complications:

• Development of stroke on chronic transfusion protocol.

• Allosensitization on chronic transfusion therapy

• Impaired neuropsychological function and abnormal MRI scan

• Abnormal Transcranial Doppler studies

• Acute chest syndrome (2 to 3 episodes of acute chest syndrome in last 3 to 4 years).

• Ferritin level < 1500 mg/ml

• Recurrent painful priapism; 3-4 episodes/year requiring intervention.

• Recurrent vaso-occlusive crisis of at least 3 to 4 episodes/year.

• Osteonecrosis of multiple bones with documented destructive changes.

• Signed informed consent

• Patients physically and psychologically capable of undergoing transplantation and a period of strict isolation.

• Ferritin < 1500

• Liver Iron Concentration < 6mg/g

Patient Inclusion Criteria for β Thalassemia major Patients less than or equal to 21 years of age with B- Thalassemia major on routine monthly transfusion protocol or with one or more of the following complications;

1. Hepatomegaly.

2. Liver biopsy revealing evidence of portal fibrosis as A) Mild B) Moderate

3. Ferritin level≤ 1500ng/ml

4. Liver Iron Concentration (LIC) < 6mg/g

Exclusion Criteria:

• Exclusion Criteria for Both Sickle Cell and β Thalassemia Major Patient

• HIV positive result confirmed by Western Blot.

• Pregnancy (Pregnancy testing for females of child-bearing age will be performed and those with a positive serum β-Human Chorionic Gonadotropin will be excluded) and lactating females.

• Creatinine greater than two times the upper limit of normal for the laboratory,

• Pulmonary disease with FVC, FEV1 or DLCO parameters < 50% predicted (corrected for hemoglobin) or stage 3 or 4 sickle lung disease.

• Cardiac insufficiency or coronary artery disease requiring treatment

• Active infection requiring systemic antibiotic therapy with antibacterial, antifungal or antiviral agents

• Lansky performance score <70%- (Appendix B)

• Acute hepatitis/biopsy evidence of cirrhosis.

• Pulmonary Hypertension