NCT03249831

A Blood Stem Cell Transplant for Sickle Cell Disease

Pilot Study to Evaluate the Safety and Feasibility of Induction of Mixed Chimerism in Sickle Cell Disease Patients With COH-MC-17: a Non-Myeloablative, Conditioning Regimen and CD4+ T-cell-depleted Haploidentical Hematopoietic Transplant

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 3 (actual)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years – 45 Years
• Healthy volunteers: Not accepted

Summary

Blood stem cells can produce red blood cells (which carry oxygen), white blood cells of the immune system (which fight infections) and platelets (which help the blood clot). Patients with sickle cell disease produce abnormal red blood cells. A blood stem cell transplant from a donor is a treatment option for patients with severe sickle cell disease. The donor can be healthy or have the sickle cell trait. The blood stem cell transplant will be given to the patient as an intravenous infusion (IV). The donor blood stem cells will then make normal red blood cells - as well as other types of blood cells - in the patient. When blood cells from two people co-exist in the patient, this is called mixed chimerism. Most children are successfully treated with blood stem cells from a sibling (brother/sister) who completely shares their tissue type (full-matched donor). However, transplant is not an option for patients who (1) have serious medical problems, and/or (2) do not have a full-matched donor. Most patients will have a relative who shares half of their tissue type (e.g. parent, child, and brother/sister) and can be a donor (half-matched or haploidentical donor). Adult patients with severe sickle cell disease were successfully treated with a half-matched transplant in a clinical study. Researchers would like to make half-matched transplant an option for more patients by (1) improving transplant success and (2) reducing transplanted-related complications. This research transplant is being tested in this Pilot study for the first time. It is different from a standard transplant because: 1. Half-matched related donors will be used, and 2. A new combination of drugs (chemotherapy) that does not completely wipe out the bone marrow cells (non-myeloablative treatment) will be used to prepare the patient for transplant, and 3. Most of the donor CD4+ T cells (a type of immune cells) will be removed (depleted) before giving the blood stem cell transplant to the patient to improve transplant outcomes. It is hoped that the research transplant: 1. Will reverse sickle cell disease and improve patient quality of life, 2. Will reduce side effects and help the patient recover faster from the transplant, 3. Help the patient keep the transplant longer and 4. Reduce serious transplant-related complications.

Detailed description

This is a pilot study to determine the safety and feasibility of the COH-MC-17 regimen and ability of the regimen to induce a mixed chimeric status in severe sickle cell disease patients (hemoglobin SS or S-βº Thalassemia). The COH-MC-17 regimen consists of a non-myeloablative regimen (cyclophosphamide, pentostatin and rabbit-anti-thymocyte globulin (ATG)) followed by a CD4+ T-cell-depleted haploidentical hematopoietic cell transplant (HaploHCT).

Conditions

• Sickle Cell Disease
• Sickle Cell Disorder
• Hemoglobinopathies
• Thalassemia
• Anemia, Sickle Cell

Interventions

Type	Name	Description
DRUG	Cyclophosphamide	Orally daily
DRUG	Pentostatin	Intravenous
DRUG	Rabbit anti-thymocyte globulin	Intravenous
DRUG	Tacrolimus	Initially IV. If patient tolerates, convert to oral.
DRUG	Mycophenolate mofetil	IV or oral
BIOLOGICAL	CD4+ T-cell-depleted Haploidentical Hematopoietic Transplant	Infusion

Timeline

• Start date: 2019-01-04
• Primary completion: 2027-01-25
• Completion: 2027-01-25
• First posted: 2017-08-15
• Last updated: 2026-03-05

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study