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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT03214354
Other study ID # TRU-17-001
Secondary ID
Status Recruiting
Phase Phase 2
First received
Last updated
Start date July 5, 2017
Est. completion date July 2028

Study information

Verified date November 2023
Source University of Calgary
Contact Tony Truong, MD, MPH
Phone 403-955-7272
Email tony.truong@ahs.ca
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The aim of this study to evaluate the safety and efficacy of a nonmyeloablative conditioning regimen for allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric patients with sickle cell disease (SCD) who have a matched related major ABO-incompatible donor. The nonmyeloablative regimen will use alemtuzumab, total body irradiation (TBI) and sirolimus for immune suppression. This study will expand the access of HSCT for patients with SCD who are currently not eligible because of donor restrictions.


Description:

Sickle cell disease (SCD) is a debilitating chronic blood disorder with multi-system end-organ damage that leads to morbidity and early mortality. The only cure for SCD is hematopoietic stem cell transplantation (HSCT), which given the risks with unrelated HSCT, is only an option for a minority of patients who have a matched sibling donor. In the field of HSCT, blood group ABO incompatibility between donor and recipient is not a contraindication and several studies do not show compromised outcomes. However, in the context of nonmyeloablative (NMA) conditioning and major ABO-incompatibility, when the recipient has existing antibodies to donor red blood cells, pure red cell aplasia (PRCA) may occur. This phase II pilot study will enroll SCD patients with a matched related major ABO-incompatible donor to determine the safety and efficacy of NMA-HSCT. Biological studies will include a plan to study and monitor red cell engraftment in this population to facilitate early detection and interventional measures to prevent and treat PRCA.


Recruitment information / eligibility

Status Recruiting
Enrollment 12
Est. completion date July 2028
Est. primary completion date July 2028
Accepts healthy volunteers No
Gender All
Age group 1 Year to 19 Years
Eligibility Inclusion Criteria: - Patients must be = 12 months and < 19 years of age at the time of study enrollment. - Patients must have sickle cell disease as defined by hemoglobin electropheresis, as follows: - homozygous Hb S disease (HbSS), - sickle-Hb C disease (HbSC), - sickle beta-plus-thalassemia (HbS/ß+), or - sickle beta-null-thalassemia (HbS/ßo) - Patients must meet standard eligibility criteria to undergo HSCT, including but not limited to one or more of the following: - history of repeated (more than 1) bony (vaso-occlusive) crisis - history of stroke - elevated transcranial Doppler velocity not eligible for hydroxyurea, as per TWiTCH trial (ie. severe vasculopathy) - history of acute chest crisis or splenic sequestration crisis - history of priapism in males - history of osteonecrosis - pulmonary hypertension as documented by tricuspid regurgitation jet velocity (TRV) > 2.5 m/s on echocardiogram - red cell allo-immunization (= 2 antibodies) during long term transfusion therapy - Sickle complications should be present despite the use of hydroxyurea, but this is not an absolute requirement, if the treating team considers the patient to be at high risk for further crisis episodes. Exclusion Criteria: - Patients who are unable to comply with or follow the study protocol. - Patients with known hypersensitivity to sirolimus, its derivatives or to any of its components.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Alemtuzumab
Alemtuzumab, Day -7 to -3. Dose: 0.2mg/kg/dose SC once daily x 5 days
Radiation:
Total Body Irradiation
TBI 300 cGy on Day -2
Drug:
Sirolimus
Sirolimus is used for GVHD prophylaxis

Locations

Country Name City State
Canada Alberta Children's Hospital Calgary Alberta

Sponsors (1)

Lead Sponsor Collaborator
University of Calgary

Country where clinical trial is conducted

Canada, 

Outcome

Type Measure Description Time frame Safety issue
Primary Incidence of pure red cell aplasia (PRCA) Clinical definition: reticulocytopenia < 10x109/L (< 1%) lasting more than 60 days after HSCT, or Pathological definition: the absence of erythroid precursors in the marrow in the setting of adequate myeloid, lymphoid and megakaryocytic precursors 6 months from enrollment
Secondary RBC chimerism measured by peripheral blood flow cytometry Peripheral blood for RBC chimerism on flow sorted erythroid precursor cells 12 months
Secondary RBC chimerism measured by bone marrow BFU-erythroid forming colonies Bone marrow will be performed between Day +45 and +60 2 months
Secondary Primary graft failure Measured by donor chimerism from peripheral blood and bone marrow 6 weeks
Secondary Secondary graft failure Measured by donor chimerism in peripheral blood and bone marrow 24 months
Secondary Disease recurrence Measured by peripheral blood Hb S level 24 months
Secondary Incidence and severity of acute GVHD Acute GVHD grade will be accessed using modified CIBMTR criteria 100 days
Secondary Incidence and severity of chronic GVHD Chronic GVHD will be accessed using the NIH consensus criteria 24 months
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