NCT02435901

Completed

Phase 1

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

Northwell Health1 site in 1 country29 target enrollmentDecember 2008

ConditionsSickle Cell Disease Beta Thalassemia-Major

InterventionsMelphalan alemtuzumab (Campath IH)Fludarabine Cyclosporine Mycophenolate mofetil Tacrolimus Hematopoietic Stem Cell Transplantation

Drugsalemtuzumab (Campath IH)Fludarabine Melphalan Cyclosporine Mycophenolate mofetil Tacrolimus

Overview

Phase: Phase 1
Intervention: Melphalan
Conditions: Sickle Cell Disease
Sponsor: Northwell Health
Enrollment: 29
Locations: 1
Primary Endpoint: Number of Participants With Sustained Cell Engraftment of Donor Cells
Status: Completed
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief 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.

Detailed 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.

Registry

clinicaltrials.gov

Start Date

December 2008

End Date

December 2019

Last Updated

4 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Northwell Health

Responsible Party

Sponsor

Eligibility 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.

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

Arms & Interventions

Reduced Intensity Regimen

Administration of reduced doses of alemtuzumab (Campath-IH) IV 3mg test dose on Day -20 followed by daily dose of 10mg/dose on Day -19 to Day -17 for patients \<10yrs or a daily dose of 15mg/dose on Day -19 to Day -17 for patients \> 10yrs. Fludarabine 35mg/m2 daily for 4 days on Day -7 to Day -4. Melphalan 70mg/m2 daily for 2 days on Day -3 and Day -2. On Day -1 Cyclosporine OR Tacrolimus will be initiated along with Mycophenolate Mofetil as a graft vs host disease prophylaxis. On Day 0 the Human Leukocyte Antigen (HLA) matched or mismatched Hematopoietic Stem Cells from either the related or unrelated donor will be infused.

Intervention: Melphalan

Reduced Intensity Regimen

Intervention: alemtuzumab (Campath IH)

Reduced Intensity Regimen

Intervention: Fludarabine

Reduced Intensity Regimen

Intervention: Cyclosporine

Reduced Intensity Regimen

Intervention: Mycophenolate mofetil

Reduced Intensity Regimen

Intervention: Tacrolimus

Reduced Intensity Regimen

Intervention: Hematopoietic Stem Cell Transplantation

Outcomes

Primary Outcomes

Number of Participants With Sustained Cell Engraftment of Donor Cells

Time Frame: 1 year

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.