Pilot Trial of Allogeneic Blood or Marrow Transplantation for Primary Immunodeficiencies

  • End date
    Dec 21, 2028
  • participants needed
  • sponsor
    National Cancer Institute (NCI)
Updated on 23 October 2022
ct scan
estimated creatinine clearance
urine tests
graft versus host disease
hematologic malignancy
mycophenolate mofetil
bone marrow transplant
ejection fraction
chest x-ray
myeloablative conditioning
bone marrow procedure
shortening fraction
reduced intensity conditioning
blood test
blood transfusion
chemotherapy regimen
pulmonary function tests
allogeneic bone marrow transplantation
urine test
autoimmune disease
therapeutic agents
lymphoproliferative disorder
hemophagocytic lymphohistiocytosis
primary immunodeficiency
Accepts healthy volunteers



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.


To see if allogeneic blood or bone marrow transplant is safe and effective in treating people with primary immunodeficiencies.


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


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.


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....


  • 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

-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

  • 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
  • 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.
  • Bone marrow is the preferred graft source. Peripheral blood stem cells are permitted
  • 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 arm. The RIC-MMF arm will receive MMF of varying durations based on a duration de-escalation schema.
  • Participants with DNA repair/telomere defects/familial cancer syndromes may receive a reduced dose (25 mg/kg/day) PTCy on days +3 and +4, in addition to sirolimus and MMF.

Condition Primary T-cell Immunodeficiency Disorders, Common Variable Immunodeficiency, Immune System Diseases, Autoimmune Lymphoproliferative, Lymphoproliferative Disorders
Treatment Reduced Intensity Conditioning, Immunosuppression Only Conditioning, Myeloablative Conditioning, GVHD Prophylaxis, Allo BMT, Immunosuppression Only Conditioning - Closed with amendment L, Myeloablative Conditioning-Closed with amendment L, Immunosuppression Only Conditioning -Closed with amendment L
Clinical Study IdentifierNCT02579967
SponsorNational Cancer Institute (NCI)
Last Modified on23 October 2022


Yes No Not Sure

Inclusion Criteria

Ages greater than equal to 18
Unrelated donors will be evaluated in accordance with existing NMDP Standard Policies and Procedures, available at: <http://bethematch.org/About-Us/Global-transplant-network/Standards/>, except for the additional requirement of EBV serostatus testing. Note that participation in this study is offered to all unrelated donors but not required for clinical donation, so it is possible that not all unrelated donors will enroll on this study

Exclusion Criteria

Unrelated donors: failure to qualify as a National Marrow Donor Program (NMDP) donor per
current NMDP Standards, available at
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