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

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Sickle Cell Disease; Pure Red Cell Aplasia; Stem Cell Transplant Complications; Red Blood Cell Disorder
• Intervention / Treatment: Drug: Alemtuzumab; Radiation: Total Body Irradiation; Drug: Sirolimus

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Tony Truong, MD, MPH; Phone Number: 403-955-7272; Email: tony.truong@ahs.ca
• Study Contact Backup: Name: Greg Guilcher, MD; Phone Number: 403-955-7272

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3B 6A8
      • Recruiting
      • Alberta Children's Hospital
      • Contact: Tony Truong, MD, MPH; Phone Number: 403-955-7272; Email: tony.truong@ahs.ca
      • Contact: Greg Guilcher, MD; Phone Number: 403-955-7272
      • Principal Investigator: Tony Truong, MD, MPH
      • Sub-Investigator: Greg Guilcher, MD
      • Sub-Investigator: Michael Leaker, MD
      • Sub-Investigator: Aisha Bruce, MD
      • Sub-Investigator: Aru Narendran, MD, PhD
      • Sub-Investigator: Victor Lewis, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 19 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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/β+), or
  • sickle beta-null-thalassemia (HbS/βo)

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Non-myeloablative conditioning	Drug: Alemtuzumab; Alemtuzumab, Day -7 to -3. Dose: 0.2mg/kg/dose SC once daily x 5 days; Other Names: Campath; Radiation: Total Body Irradiation; TBI 300 cGy on Day -2; Other Names: TBI; Drug: Sirolimus; Sirolimus is used for GVHD prophylaxis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
RBC chimerism measured by peripheral blood flow cytometry	Peripheral blood for RBC chimerism on flow sorted erythroid precursor cells	12 months
RBC chimerism measured by bone marrow BFU-erythroid forming colonies	Bone marrow will be performed between Day +45 and +60	2 months
Primary graft failure	Measured by donor chimerism from peripheral blood and bone marrow	6 weeks
Secondary graft failure	Measured by donor chimerism in peripheral blood and bone marrow	24 months
Disease recurrence	Measured by peripheral blood Hb S level	24 months
Incidence and severity of acute GVHD	Acute GVHD grade will be accessed using modified CIBMTR criteria	100 days
Incidence and severity of chronic GVHD	Chronic GVHD will be accessed using the NIH consensus criteria	24 months

Collaborators and Investigators

• Sponsor: University of Calgary

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2017
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: July 5, 2017
• First Submitted That Met QC Criteria: July 10, 2017
• First Posted (Actual): July 11, 2017

Study Record Updates

• Last Update Posted (Actual): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: stem cell transplant; sickle cell disease; nonmyeloablative; pure red cell aplasia; red blood cell engraftment
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Anemia, Sickle Cell; Red-Cell Aplasia, Pure; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Investigative Techniques; Therapeutics; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Macrolides; Lactones; Radiotherapy; Alemtuzumab; Sirolimus; Whole-Body Irradiation
• Other Study ID Numbers: TRU-17-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No