A Blood Stem Cell Transplant for Sickle Cell Disease

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.

Conditions

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

Interventions

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

Sponsors & Collaborators

• California Institute for Regenerative Medicine (CIRM)

  collaborator OTHER

• City of Hope Medical Center

  lead OTHER

Principal Investigators

• Joseph Rosenthal, MD · City of Hope Medical Center

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

45 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-01-04

Primary Completion

2027-01-25

Completion

2027-01-25

FDA Drug

Yes

Countries

• United States

Study Locations