Pilot Study of Reduced-Intensity Hematopoietic Stem Cell Transplant of DOCK8 Deficiency
- DOCK8 deficiency is a genetic disorder that affects the immune system and can lead to severe recurrent infections and possible death from blood poisoning or certain types of cancers, including blood cancers. Stem cell transplants from matching or closely related donors (allogenic stem cell transplants) may be a life-saving treatment for this condition. However, stem cell transplants can have serious complications, because they tend to be performed with very high doses of chemotherapy and/or radiation. Reduced-intensity stem cell transplants use smaller doses of radiation and chemotherapy to weaken but not completely eliminate the recipient s stem cells and immunity. Researchers are exploring whether reduced-intensity stem cell transplants in people with DOCK8 deficiency may decrease the chance of graft rejection and the overall side effects of the transplant.
- To evaluate the safety and effectiveness of reduced-intensity allogeneic stem cell transplant as a treatment for DOCK8 deficiency.
- Donors: Healthy individuals between 4 and 60 years of age who are matched with a recipient.
- Recipient: Individuals between 10 and 60 years of age who have DOCK8 deficiency, have suffered two or more life-threatening infections, have either low white blood cell levels or have had certain types of cancer (lymphoma or squamous cell carcinoma), and have a stem cell donor.
- All participants will be screened with a physical examination and medical history.
- Donors will receive injections of filgrastim to release stem cells into the blood. After 5 days of filgrastim injections, donors will have apheresis to donate stem cells and white blood cells that are present in the blood.
- Donors who are not eligible to receive filgrastim will provide the stem cells through bone marrow donation.
- From 7 days before the stem cell transplant, recipients will be admitted to the inpatient unit of the National Institutes of Health Clinical Center and will receive regular doses of cyclophosphamide, fludarabine, and radiation to suppress their immune system and prepare them for the transplant.
- From 3 days before the stem cell transplant, recipients will receive the drugs tacrolimus and sirolimus to help prevent complications from the transplant.
- After the initial chemotherapy and radiation, recipients will receive the donated stem cells as a single infusion. Recipients may also receive white blood cells from their stem cell donor to encourage acceptance of the stem cells.
- After the stem cell and white blood cell transplant, recipients will remain in inpatient care for up to 1 month, and will be followed with regular visits for up to 3 years with periodic visits thereafter to evaluate the success of the transplant and any side effects.
Procedure: Allogeneic HSC transplant
Procedure: Total Body Irradiation (TBI)
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Related and Unrelated Donor Hematopoietic Stem Cell Transplant of DOCK8 Deficiency|
- To determine whether reduced-intensity allogeneic (HSCT) reconstitutes T-lymphocyte, B-lymphocyte, and NK cell populations with normal donor cells and reverses the clinical phenotype of severe recurrent in patients with DOCK8. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- To determine the safety of this allogeneic transplant regimen in DOCK8 by assessing transplant related toxicity, the incidence of acute and chronic GVHD, immune reconstitution, overall survival, and disease-free survival. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
|Study Start Date:||July 2010|
|Contact: Kristen Cole, R.N.||(301) email@example.com|
|Contact: Dennis D Hickstein, M.D.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office (888) NCI-1937|
|Principal Investigator:||Dennis D Hickstein, M.D.||National Cancer Institute (NCI)|