Stem Cell Transplant for Sickle Cell Disease

Recruiting in Palo Alto (17 mi)

Overseen by Joseph Rosenthal, MD

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: City of Hope Medical Center

No Placebo Group

Trial Summary

What is the purpose of this trial?

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.

Research Team

Joseph Rosenthal, MD

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

This trial is for patients with severe sickle cell disease who have had multiple joint issues, strokes, or vaso-occlusive crises despite treatment. They need a related half-matched donor (like a parent or sibling) and can't have had prior transplants. Women must not be pregnant and agree to use contraception.

Inclusion Criteria

I have had a stroke or neurological issues lasting more than a day.

I have been diagnosed with sickle cell disease (SS or S-βº Thalassemia).

My condition is considered severe due to one or more specific factors.

Exclusion Criteria

I have serious liver scarring and have been on blood transfusion therapy for over 6 months.

I am not pregnant or breastfeeding.

I have had a bone marrow transplant in the past.

Treatment Details

Interventions

• CD4+ T-cell-depleted Haploidentical Hematopoietic Transplant (Hematopoietic Stem Cell Transplantation)
• Cyclophosphamide (Chemotherapy)
• Mycophenolate mofetil (Immunosuppressant)
• Pentostatin (Chemotherapy)
• Rabbit anti-thymocyte globulin (Immunosuppressant)
• Tacrolimus (Immunosuppressant)

Trial Overview The study tests a blood stem cell transplant from a half-matched relative using new chemotherapy that's less harsh on bone marrow. It aims to create mixed chimerism where the patient's body accepts both their own and the donor's blood cells, potentially reversing sickle cell disease.

Participant Groups

Group I: COH-MC-17 and immunosuppressants Experimental Treatment 6 Interventions

Participants receive COH-MC-17: a 21-day nonmyeloablative conditioning regimen (cyclophosphamide, pentostatin and rabbit anti-thymocyte globulin), followed by CD4+ T-cell-depleted Haploidentical Hematopoietic Transplant on Day 0. Immunosuppressants (tacrolimus and mycophenolate mofetil) given on Day -1 onwards until discontinuation post-transplant. The minimally manipulated transplant product is manufactured using the CliniMACS device.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

Robert Stone

City of Hope Medical Center

Chief Executive Officer since 2014

Juris Doctorate from the University of Chicago, Bachelor's degree in Political Science from the University of Redlands

Sumanta (Monty) Pal

City of Hope Medical Center

Chief Medical Officer since 2023

MD

California Institute for Regenerative Medicine (CIRM)

Collaborator

Trials

70

Recruited

3,300+

Jonathan Thomas

California Institute for Regenerative Medicine (CIRM)

Chief Executive Officer

BA in Biology and History from Yale University, JD from Yale Law School, PhD in Commonwealth History from Oxford University

Rosa Canet-Avilés

California Institute for Regenerative Medicine (CIRM)

Chief Medical Officer since 2024

PhD in Neuroscience from Leeds University, BS in Organic Chemistry from Central University of Barcelona