Nonmyeloablative Stem Cell Transplant for Sickle Cell Anemia and Thalassemia

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen byMatthew M Hsieh, M.D.

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial tests if using low dose radiation and certain drugs can help patients with beta-thalassemia or sickle cell disease better accept donor stem cells. The treatment aims to suppress the immune system to reduce rejection of the new cells.

Research Team

Matthew M Hsieh, M.D.

Principal Investigator

National Heart, Lung, and Blood Institute (NHLBI)

Eligibility Criteria

This trial is for people aged 4 and older with severe sickle cell disease or beta-thalassemia, who are at high risk of complications not improved by other treatments. They must have a matched family donor willing to donate stem cells. Exclusions include serious infections within the last month, pregnancy, lactation, or any major illness that could interfere with transplant survival.

Inclusion Criteria

I am at least 4 years old.

I am eligible for hydroxyurea treatment or a stem cell transplant.

Negative beta-HCG, when applicable

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Exclusion Criteria

I do not have any major illnesses or organ failures that would make a stem cell transplant impossible.

I need considerable assistance and am unable to carry out any work activities.

Evidence of uncontrolled bacterial, viral, or fungal infections within one month prior to starting the conditioning regimen

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Treatment Details

Interventions

Cyclophosphamide (Immunosuppressive Agent)
Pentostatin (Immunosuppressive Agent)
Radiotherapy (Radiation)
Sirolimus (Immunosuppressive Agent)

Trial OverviewThe study tests a new transplant method using low-dose radiation and immunosuppressive drugs (cyclophosphamide, pentostatin, sirolimus) to see if they help patients better accept donated stem cells. Participants will undergo various procedures including blood tests and bone marrow sampling before receiving the treatment in hospital.

Participant Groups

3Treatment groups

Experimental Treatment

Group I: Participants with pre-existing antibodies and SCD or Beta-thalassemia receiving stem cell transplantExperimental Treatment5 Interventions

Participants with pre-existing antibodies and Sickle Cell Disease (SCD) or Beta-thalassemia receiving stem cell transplant. Pentostatin given on days -21, -17, -13, -9 and oral cyclophosphamide from days -21 to -8, with the intention to be administered in the outpatient setting. Alemtuzumab on days 7 to 3, and 300 cGy TBI on day 2. Sirolimus started at a loading dose of 5mg PO every 4 hours for three doses on day -1 and adjusted to maintain trough levels between 10-15 ng/mL. The PBSC graft targeted to deliver .10 x 106 CD34+ cells/kg (minimum .5 x 106) and infused on day 0.

Group II: Human Leukocyte Antigens (HLA) Matched Related Stem Cell DonorExperimental Treatment1 Intervention

Participants received filgrastim to mobilize peripheral blood stem cells for apheresis collection. Collected stem cells of donor will then be infused to HLA matched sibling.

Group III: Female participants with SCD or Beta-thalassemia receiving stem cell transplant with male donorExperimental Treatment5 Interventions

Female participants with Sickle Cell Disease (SCD) or Beta-thalassemia receiving stem cell transplant with male donor. Pentostatin given on days -21, -17, -13, -9 and oral cyclophosphamide from days -21 to -8, with the intention to be administered in the outpatient setting. Alemtuzumab on days 7 to 3, and 300 cGy TBI on day 2. Sirolimus started at a loading dose of 5mg PO every 4 hours for three doses on day -1 and adjusted to maintain trough levels between 10-15 ng/mL. The PBSC graft targeted to deliver .10 x 106 CD34+ cells/kg (minimum .5 x 106) and infused on day 0.

Cyclophosphamide is already approved in Canada, Japan for the following indications: