Nonmyeloablative Stem Cell Transplant in Children With Sickle Cell Disease and a Major ABO-Incompatible Matched Sibling Donor

Sickle Cell Disease Clinical Trial

— Sickle-AID  

Official title:

A Phase II Pilot Study of Nonmyeloablative Conditioning Hematopoietic Stem Cell Transplantation in Children With Sickle Cell Disease Who Have a Matched Related Major ABO-Incompatible Donor (Sickle-AID)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03214354
• Other study ID #: TRU-17-001
• Status: Recruiting
• Phase: Phase 2
• 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
• 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.

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Pure Red Cell Aplasia
• Red Blood Cell Disorder
• Red-Cell Aplasia, Pure
• Sickle Cell Disease
• Stem Cell Transplant Complications

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