Pilot Trial of Allogeneic Blood or Marrow Transplantation for Primary Immunodeficiencies

Immune System Diseases Clinical Trial

Official title: Pilot Trial of Allogeneic Blood or Marrow Transplantation for Primary Immunodeficiencies

Status Recruiting

Clinical Trial 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....

Clinical Trial 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-host disease (aGVHD)-free, graft failure-free survival at day +180 after allo BMT, analyzed separately by conditioning arm/cohort Eligibility: - Patients age greater than or equal to 4 through 75 years - PID deemed to be of sufficient past severity to warrant allo BMT, by meeting the two criteria below: - PID as defined by identified genetic defect or, in the absence of a mutation, patients with an immune defect potentially amenable to allo BMT who meet the clinical history criteria below may be eligible - Clinical history of at least two of the following: - Life-threatening, organ-threatening, or severely disfiguring infection - Protracted or recurrent infections - Infection with an opportunistic organism - Chronic elevation in the blood of a latent virus - Evidence of immune dysregulation - Hypogammaglobulinemia/dysglobulinemia - Hematologic malignancy or lymphoproliferative disorder - Virus-associated solid tumor malignancy or pre-cancerous lesion - At least one 7-8/8 (9-10/10) HLA-matched related or unrelated donor, or an HLA-haploidentical related donor - Adequate end-organ function - Consensus opinion by the investigative team that the patient has the potential to benefit from transplant despite existing, non-hematopoietic organ dysfunction - Not pregnant or breastfeeding - HIV negative - Disease status: patients with malignancy should be referred in remission for evaluation, except in the case of virus-associated malignancy who may be referred at any time Design: - The study will have two arms that vary in mycophenolate mofetil (MMF) duration. - RIC and RIC-MMF arms: pentostatin 4 mg/m2/day IV on days -11 and -7, low-dose cyclophosphamide orally daily on days -11 through -4; busulfan IV, pharmacokinetically dosed, on days -3 and -2. - RIC-SHORT arm: pentostatin 4 mg/m2/day IV on days -9 and -5, low-dose cyclophosphamide orally daily on days -9 through -2; busulfan IV, pharmacokinetically dosed, on days -3 and -2. - Bone marrow is the preferred graft source. Peripheral blood stem cells are permitted on RIC-MMF arm but not on RIC-SHORT arm. - GVHD prophylaxis: - High-dose, post-transplantation cyclophosphamide (PTCy) on days +3 and +4, sirolimus on days +5 through +90, and mycophenolate mofetil (MMF) on days +5 through +35 for all arms except the RIC-MMF and RIC-SHORT arm. The RICMMF arm will receive MMF of varying durations based on a duration de-escalation schema. - RIC-SHORT: Reduced-dose, post-transplantation cyclophosphamide (PTCy) on days +3 and +4, sirolimus on days +5 through +90, and mycophenolate mofetil (MMF) on days +5 through +18 for all arms. ;

Related Conditions & MeSH terms

• Autoimmune Lymphoproliferative
• Common Variable Immunodeficiency
• Immune System Diseases
• Immunologic Deficiency Syndromes
• Lymphoproliferative Disorders
• Primary Immunodeficiency Diseases
• Primary T-cell Immunodeficiency Disorders

• NCT number: NCT02579967
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Dimana Dimitrova, M.D.
• Phone: (240) 858-3647
• Email: dimana.dimitrova@nih.gov
• Status: Recruiting
• Phase: Phase 2
• Start date: November 19, 2015
• Completion date: December 21, 2028