HSCT For Patients With High Risk Hemoglobinopathies Using Reduced Intensity

Sickle Cell Disease Clinical Trial

Official title:

ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT) IN PATIENTS WITH HIGH RISK HEMOGLOBINOPATHIES LIKE SICKLE CELL DISEASE AND β-THALESSEMIA-MAJOR USING REDUCED INTENSITY CONDITIONING REGIMEN

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02435901
• Other study ID #: 08057
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: December 2008
• Est. completion date: December 2019

Study information

• Verified date: July 2021
• Source: Northwell Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Standard myeloablative regimens are toxic to non-hematopoietic tissue and are associated with treatment related mortality and morbidity (TRM). Preparative regimens that are not myeloablative are associated with a greatly decreased incidence of TRM. In addition to providing a less toxic regimen, the reduced intensity chemotherapy preparative regimen also remains immunosuppressive enough to allow donor engraftment. Recent report of non-myeloablative regimens which resulted in engraftment of allogeneic stem cell in hematological malignancies raises the possibility that this conditioning regimen might be useful in achieving engraftment in non hematological disorder. In an effort to achieve stable engraftment with any suitable donor stem cell source and to minimize toxicity the investigators have developed a new reduced intensity conditioning regimen for high risk hemoglobinopathies with the main aim of significantly suppressing the recipient's immune system and facilitate engraftment. Non-myeloablative or reduced-intensity immunosuppressive preparative regimens have achieved a stable, mixed chimerism engraftment and successful allogeneic bone marrow transplants.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: December 2019
• Est. primary completion date: March 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 21 Years

Eligibility

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-ß-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 ß 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 ß 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 ß-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

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Beta Thalassemia-Major
• beta-Thalassemia
• Hemoglobinopathies
• Sickle Cell Disease
• Thalassemia

Intervention

Drug:
• alemtuzumab (Campath IH)
Alemtuzumab (Campath IH) is given daily over first 4 days, Day -20 to Day -17
• Fludarabine
Fludarabine 35/m2 is given daily over 4 days on Day -7 to Day -4.
• Melphalan
Melphalan 70mg/m2 is given daily over 2 days on Day -3 to Day -2.
• Cyclosporine
Immunosuppressant to prevent graft vs host disease is given on Day -1 prior to stem cell infusion
• Mycophenolate mofetil
Immunosuppressant to prevent graft vs host disease is given on Day -1.
• Tacrolimus
Immunosuppressant to prevent graft vs host disease is given Day -1 prior to stem cell infusion

Biological:
• Hematopoietic Stem Cell Transplantation
Human Leukocyte Antigen (HLA) matched or mismatched; related or unrelated hematopoietic stem cells to be transplanted on Day 0.

Locations

Country	Name	City	State
United States	Cohen Children's Medical Center of New York	New Hyde Park	New York

Sponsors (1)

Lead Sponsor	Collaborator
Northwell Health

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Sustained Cell Engraftment of Donor Cells	Sustained stem cell engraftment of donor cells will be evaluated by chimerism (FISH fluorescence in situ hybridization OR VNTR (Variable Number of Tandem Repeats), based on recipient/donor gender, at 30 days, 100 days, 6 months and 1 year following the use of reduced intensity conditioning.	1 year
Secondary	Assessment of Treatment Related Mortality and Morbidity	Patients will be evaluated for incidence and severity of graft versus host disease, infection, and cardiopulmonary complications.	2 years
Secondary	Event Free Survival; Number of Participants Who Survived at 2 Years	29 participants will be evaluated for Event Free Survival.	2 years