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

NCT03214354 | Recruiting Phase 2 DMC

• 1 other identifier: TRU-17-001
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Sickle Cell Disease; Stem Cell Transplant Complications; Red Blood Cell Disorder; Pure Red Cell Aplasia

Keywords

sickle cell disease; stem cell transplant; red blood cell engraftment; nonmyeloablative; pure red cell aplasia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• RBC chimerism measured by peripheral blood flow cytometry

  12 months

• RBC chimerism measured by bone marrow BFU-erythroid forming colonies

  2 months

• Primary graft failure

  6 weeks

• Secondary graft failure

  24 months

• Disease recurrence

  24 months

Study Arms (1)

Non-myeloablative conditioning

EXPERIMENTAL

Non-myeloablative conditioning

Drug: Alemtuzumab; Radiation: Total Body Irradiation; Drug: Sirolimus

Interventions

Alemtuzumab DRUG

Alemtuzumab, Day -7 to -3. Dose: 0.2mg/kg/dose SC once daily x 5 days

Also known as: Campath

Non-myeloablative conditioning

Total Body Irradiation RADIATION

TBI 300 cGy on Day -2

Also known as: TBI

Non-myeloablative conditioning

Sirolimus DRUG

Sirolimus is used for GVHD prophylaxis

Non-myeloablative conditioning

Eligibility Criteria

• Age: 1 Year - 19 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Calgary: lead

Study Sites (1)

Alberta Children's Hospital

Calgary, Alberta, T3B 6A8, Canada

RECRUITING

MeSH Terms

Conditions

Anemia, Sickle Cell; Red-Cell Aplasia, Pure

Interventions

Alemtuzumab; Whole-Body Irradiation; Sirolimus

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Radiotherapy; Therapeutics; Investigative Techniques; Macrolides; Lactones; Organic Chemicals

Central Study Contacts

Tony Truong, MD, MPH

CONTACT

403-955-7272; tony.truong@ahs.ca

Greg Guilcher, MD

CONTACT

403-955-7272

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Pediatric Hematologist/Oncologist

Model Details: Phase II pilot, non-randomized, prospective study to evaluate the safety and efficacy of a nonmyeloablative conditioning allogeneic stem cell transplantation for patients with sickle cell disease who have a matched related major ABO-incompatible donor.

Study Record Dates

• First Submitted: July 5, 2017
• First Posted: July 11, 2017
• Study Start: July 5, 2017
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)