Clinical trial NCT00029393: Induction of Stable Chimerism for Sickle Cell Anemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Blood Disease
Hematopoietic Stem Cell Transplantation
Anemia, Sickle Cell
Lead sponsor: National Heart, Lung, and Blood Institute (NHLBI)
Sponsor class: NIH
First posted: 2002-01-11
Sex: ALL
Maximum age (years): 100
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: To investigate a modified hematopoeitic cell transplantation (HCT) procedure for sickle cell disease that significantly reduces the toxicity of HCT, yet retains its therapeutic benefit.

Detailed description: BACKGROUND:

Hematopoietic cell transplantation (HCT) has curative potential for individuals with sickle cell disease. While the results of conventional HCT have been good, this treatment carries risks of significant short- term and longterm toxicities. For this reason, HCT has been reserved for children who have experienced severe symptoms that predict a poor outcome. Of interest, some patients developed stable donor-host hematopoietic chimerism after conventional HCT. Due to a natural enrichment of donor erythrocytes in the blood, those who developed stable chimerism had a significant clinical benefit, even when there was a minority of donor cells. These observations have paralleled efforts to develop less-toxic, non-myeloablative preparative regiments for transplantation, proved first in a canine model of transplantation, and subsequently translated successfully in a clinical trial for older adults with hematological malignancies.

DESIGN NARRATIVE:

Multicenter open-label phase I-II study in 30 children with sickle cell disease that combines a non-myeloablative pre-transplant hematopoietic cell transplantation (HCT) therapy with modulated post-grafting immunosuppression to control host-versus-graft and graft-versus-host reactions. The approach relies on the ability to establish and maintain donor-host chimerism. The primary study endpoint is stable donor cell engraftment; secondary endpoints measure the impact of therapy on sickle cell-related symptoms and end-organ damage (disease-free survival, patient survival, graft-versus-host disease, complications etc). The trial will be conducted within the existing network of Comprehensive Sickle Cell Centers, and will be centrally coordinated by the Sickle Cell Coordinating Center.

Eligibility criteria: No eligibility criteria

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: UCSF Benioff Children's Hospital Oakland
name: Mark Walters
References:
citation: Walters MC, Patience M, Leisenring W, Rogers ZR, Aquino VM, Buchanan GR, Roberts IA, Yeager AM, Hsu L, Adamkiewicz T, Kurtzberg J, Vichinsky E, Storer B, Storb R, Sullivan KM; Multicenter Investigation of Bone Marrow Transplantation for Sickle Cell Disease. Stable mixed hematopoietic chimerism after bone marrow transplantation for sickle cell anemia. Biol Blood Marrow Transplant. 2001;7(12):665-73. doi: 10.1053/bbmt.2001.v7.pm11787529.
citation: Atkins RC, Walters MC. Haematopoietic cell transplantation in the treatment of sickle cell disease. Expert Opin Biol Ther. 2003 Dec;3(8):1215-24. doi: 10.1517/14712598.3.8.1215.
citation: Iannone R, Casella JF, Fuchs EJ, Chen AR, Jones RJ, Woolfrey A, Amylon M, Sullivan KM, Storb RF, Walters MC. Results of minimally toxic nonmyeloablative transplantation in patients with sickle cell anemia and beta-thalassemia. Biol Blood Marrow Transplant. 2003 Aug;9(8):519-28. doi: 10.1016/s1083-8791(03)00192-7.
citation: Horan JT, Liesveld JL, Fenton P, Blumberg N, Walters MC. Hematopoietic stem cell transplantation for multiply transfused patients with sickle cell disease and thalassemia after low-dose total body irradiation, fludarabine, and rabbit anti-thymocyte globulin. Bone Marrow Transplant. 2005 Jan;35(2):171-7. doi: 10.1038/sj.bmt.1704745.