NCT02579967

Pilot Trial of Allogeneic Blood or Marrow Transplantation for Primary Immunodeficiencies

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 354 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 4 Years – 75 Years
• Healthy volunteers: Accepted

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....

Detailed 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 \>= 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.

Conditions

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

Interventions

Type	Name	Description
DRUG	Immunosuppression 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)
DRUG	Reduced 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.
DRUG	Myeloablative 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)
DRUG	GVHD 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.
PROCEDURE	Allo BMT	Allogeneic blood or marrow transplantation

Timeline

• Start date: 2015-11-19
• Primary completion: 2031-12-31
• Completion: 2036-12-31
• First posted: 2015-10-20
• Last updated: 2026-04-06

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study