Pilot Trial of Allogeneic Blood or Marrow Transplantation for Primary Immunodeficiencies
National Cancer Institute (NCI)
Summary
Background: Allogeneic blood or marrow transplant is when stem cells are taken from one person s blood or bone marrow and given to another person. Researchers think this may help people with immune system problems. Objective: To see if allogeneic blood or bone marrow transplant is safe and effective in treating people with primary immunodeficiencies. Eligibility: Donors: Healthy people ages 4 or older Recipients: People ages 4-75 with a primary immunodeficiency that may be treated with allogeneic blood or marrow transplant Design: Participants will be screened with medical history, physical exam, and blood tests. Participants will have urine tests, EKG, and chest x-ray. Donors will have: Bone marrow harvest: With anesthesia, marrow is taken by a needle in the hipbone. OR Blood collection: They will have several drug injections over 5-7 days. Blood is taken by IV in one arm, circulates through a machine to remove stem cells, and returned by IV in the other arm. Possible vein assessment or pre-anesthesia evaluation Recipients will have: Lung test, heart tests, radiology scans, CT scans, and dental exam Possible tissue biopsies or lumbar puncture Bone marrow and a small piece of bone removed by needle in the hipbone. Chemotherapy 1-2 weeks before transplant day Donor stem cell donation through a catheter put into a vein in the chest or neck Several-week hospital stay. They will take medications and may need blood transfusions and additional procedures. After discharge, recipients will: Remain near the clinic for about 3 months. They will have weekly visits and may require hospital readmission. Have multiple follow-up visits to the clinic in the first 6 months, and less frequently for at least 5 years.
Description
Background: * Primary immunodeficiency diseases (PIDs) are conditions associated with major quantitative or qualitative immunologic abnormalities that are, in most cases, due to defects in cells of hematopoietic origin * Participants with PID can have life-threatening complications including malignancy, recurrent infection, and autoimmunity/immune dysregulation * Allogeneic blood or marrow transplantation (allo BMT) has the potential to cure the immune defect in PID and thereby reduce the morbidity and mortality associated with these diseases Objectives: -To estimate the acute graft-versus-…
Eligibility
- Age range
- 4–75 years
- Sex
- All
- Healthy volunteers
- Yes
* INCLUSION CRITERIA - RECIPIENT: * Patients age \>= 4 through 75 years * PID deemed to be of sufficient past severity to warrant allo BMT, by meeting the two criteria below: 1. PID as defined by identified genetic defect or, in the absence of a PID-associated genetic mutation, patients with an immune defect potentially amenable to allo BMT who meet the clinical history criteria below may be eligible upon discussion with the PI * Mutations should be confirmed in a CLIA-certified laboratory, if such testing is available. * Patients without a mutation must be deemed eligible and ap…
Interventions
- DrugImmunosuppression Only Conditioning -Closed with amendment L
Pentostatin 4 mg/m2/day IV on days -9 and -5, cyclophosphamide 5 mg/kg orally daily on days -9 through -2 (Closed with amendment L)
- DrugReduced Intensity Conditioning
pentostatin 4 mg/m2/day IV on days -11 and -7, cyclophosphamide 3 mg/kg orally daily on days -11 through -4; busulfan IV, pharmokinetically dosed, on days -3 and -2.
- DrugMyeloablative Conditioning-Closed with amendment L
Pentostatin 4 mg/m2/day IV on days -13 and -9, low-dose cyclophosphamide orally daily on days -13 through -6; busulfan IV, pharmokinetically dosed, on days -5, -4, -3, and -2. (Closed with amendment L)
- DrugGVHD Prophylaxis
High-dose, post-transplantation cyclophosphamide (PTCy) 25-50 mg/kg on days +3 and +4, sirolimus 6 mg on days +5 through +90, and mycophenolate mofetil (MMF) on days +5 through 0, +18, +25, or +35 depending on treatment arm and cohort.
- ProcedureAllo BMT
Allogeneic blood or marrow transplantation
Locations (2)
- National Institutes of Health Clinical CenterBethesda, Maryland
- National Marrow Donor ProgramMinneapolis, Minnesota