Clinical trial NCT02435901
Conditions: Sickle Cell Disease Beta Thalassemia-Major
Keywords: Reduced Intensity Conditioning Regimen
Sponsor: Northwell Health
Start date: 2008-12-01; Completion date: 2019-12-01
Enrollment: 29 participants; Allocation: NA; Intervention model: SINGLE_GROUP

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.

Arms: arm 1: 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.
Interventions: intervention 1: alemtuzumab (Campath IH) intervention 2: Fludarabine intervention 3: Melphalan intervention 4: Cyclosporine intervention 5: Mycophenolate mofetil intervention 6: Tacrolimus intervention 7: Hematopoietic Stem Cell Transplantation
Intervention descriptions: intervention 1: Alemtuzumab (Campath IH) is given daily over first 4 days, Day -20 to Day -17 intervention 2: Fludarabine 35/m2 is given daily over 4 days on Day -7 to Day -4. intervention 3: Melphalan 70mg/m2 is given daily over 2 days on Day -3 to Day -2. intervention 4: Immunosuppressant to prevent graft vs host disease is given on Day -1 prior to stem cell infusion intervention 5: Immunosuppressant to prevent graft vs host disease is given on Day -1. intervention 6: Immunosuppressant to prevent graft vs host disease is given Day -1 prior to stem cell infusion intervention 7: Human Leukocyte Antigen (HLA) matched or mismatched; related or unrelated hematopoietic stem cells to be transplanted on Day 0.

Protocol documents:
Prot_SAP_000.pdf: