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