Pilot Trial of Allogeneic Blood or Marrow Transplantation for Primary Immunodeficiencies
2 other identifiers
interventional
354
1 country
2
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Nov 2015
Longer than P75 for phase_2
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 16, 2015
CompletedFirst Posted
Study publicly available on registry
October 20, 2015
CompletedStudy Start
First participant enrolled
November 19, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2031
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2036
April 29, 2026
April 22, 2026
16.1 years
October 16, 2015
April 28, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
For the RIC-SHORT arm: To estimate the aGVHD-free, graft failure-free survival
Proportion of participants without GVHD
+180 after allo BMT
For the RIC : To estimate the aGVHD-free, graft failure-free survival
Proportion of participants without GVHD
+180 after allo BMT
For the RIC-MMF arm: To determine the shortest duration of MMF that can be safely administered without excessive rates of graft failure or acute grade 3-4 GVHD
Shortest duration of MMF
Duration de-escalation design
Secondary Outcomes (9)
Transplant-related mortality
+180 and 1 year post transplant
Secondary graft failure
1 year post transplant
Overall survival
1 year post transplant
Kinetics and durability of lineage-specific donor chimerism
days +28 and +42
Kinetics and durability of engraftment
days +28, +42, +60, +100, +180, and 1 year after allo BMT
- +4 more secondary outcomes
Study Arms (6)
1/ IOC Arm-Closed with amendment L (07/05/2019)
EXPERIMENTALImmunosuppression Only Conditioning Arm
2/ RIC Arm - Closed with Amendment L (07/05/2019)
EXPERIMENTALReduced Intensity Conditioning Arm
3/ MAC Arm-Closed with amendment L (07/05/2019)
EXPERIMENTALMyeloablative Conditioning Arm
4/ RIC-MMF Arm
EXPERIMENTALReduced Intensity Conditioning with MMF duration de-escalation design
5/ Donor Arm
NO INTERVENTIONDonor
6/ RIC-SHORT Arm
EXPERIMENTALReduced Intensity Conditioning with shortened duration and dose-reduced PTCy
Interventions
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.
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)
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)
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.
Allogeneic blood or marrow transplantation
Eligibility Criteria
You may qualify if:
- 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 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 appropriate for allo BMT by the PI. Some patients may meet the clinical history criteria listed below, but will not be eligible if it is thought that their clinical history is due to a condition apart from an immune defect. In addition, patients with a PID of mild severity, such as those with selective IgA deficiency, may meet at least two of the clinical history criteria, but may be deemed inappropriate for allo BMT by the PI if it is felt that the risks of the procedure outweigh the severity of the disease.
- Clinical history of at least two of the following:
- Life-threatening, organ-threatening, or severely disfiguring infection
- Protracted or recurrent infections requiring unusually long or repeated courses of antibiotics
- Infection with an opportunistic organism
- Chronic elevation in the blood (\>=2 documented elevations over a period of 6 months or longer) of a latent virus (EBV, CMV, HHV6, HHV8, etc.)
- Evidence of immune dysregulation, as manifested by autoimmune disease, atopy, hemophagocytic lymphohistiocytosis/macrophage activation syndrome, granulomas, splenomegaly, or lymphadenopathy
- Patients with hemophagocytic lymphohistiocytosis or macrophage activation syndrome related to an underlying lymphoma with no other clinical history suggestive of a primary immunodeficiency will not be eligible
- Hypogammaglobulinemia, dysglobulinemia, or impaired response to vaccination
- Hematologic malignancy or lymphoproliferative disorder
- Tissue diagnosis should be confirmed by NCI Department of Pathology, if prior biopsies are available
- +13 more criteria
You may not qualify if:
- Patients who are receiving any other investigational agents, with the exception of virus-specific cytotoxic T-cells for the treatment of viral infection/reactivation prior to allo BMT.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents (cyclophosphamide, busulfan, pentostatin, sirolimus, MMF, filgrastim or filgrastim biosimilar) used in the study
- Active psychiatric disorder which may compromise compliance with the transplant protocol, or which does not allow for appropriate informed consent
- Active central nervous system (CNS) involvement by malignancy, except in cases of virus-associated malignancies with CNS involvement in which case the patient may benefit from the transplant to control the malignancy.
- MAGT1 mutation and active need to take anti-platelet agents and/or therapeutic anti-coagulation that cannot be interrupted during aplasia.
- HIV positive or other acquired immunodeficiency that, as determined by the PI, interferes with the assessment of PID severity and/or the attribution of clinical manifestations of immunodeficiency to a PID.
- Lack of adequate central venous access potential
- Ages \>= 4
- Related donor deemed suitable and eligible and willing to donate per clinical evalations who are additionally willing to donate blood, urine, and marrow specimens for research. Related donors will be evaluated in accordance with existing Standard Policies and Procedures for determination of eligibility and suitability for clinical donation. Note that participation in this study is offered to all related donors but is not required for clinical donation, so it is possible that not all related donors will enroll on this study.
- None
- Ages \>= 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.
- Unrelated donors: failure to qualify as a National Marrow Donor Program (NMDP) donor per current NMDP Standards, available at: http://bethematch.org/About-Us/Global-transplant-network/Standards/.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
National Marrow Donor Program
Minneapolis, Minnesota, 55413-1753, United States
Related Publications (3)
Bashey A, Zhang X, Sizemore CA, Manion K, Brown S, Holland HK, Morris LE, Solomon SR. T-cell-replete HLA-haploidentical hematopoietic transplantation for hematologic malignancies using post-transplantation cyclophosphamide results in outcomes equivalent to those of contemporaneous HLA-matched related and unrelated donor transplantation. J Clin Oncol. 2013 Apr 1;31(10):1310-6. doi: 10.1200/JCO.2012.44.3523. Epub 2013 Feb 19.
PMID: 23423745BACKGROUNDMariotti J, Taylor J, Massey PR, Ryan K, Foley J, Buxhoeveden N, Felizardo TC, Amarnath S, Mossoba ME, Fowler DH. The pentostatin plus cyclophosphamide nonmyeloablative regimen induces durable host T cell functional deficits and prevents murine marrow allograft rejection. Biol Blood Marrow Transplant. 2011 May;17(5):620-31. doi: 10.1016/j.bbmt.2010.11.029. Epub 2010 Dec 3.
PMID: 21130889BACKGROUNDKang E, Gennery A. Hematopoietic stem cell transplantation for primary immunodeficiencies. Hematol Oncol Clin North Am. 2014 Dec;28(6):1157-70. doi: 10.1016/j.hoc.2014.08.006. Epub 2014 Sep 16.
PMID: 25459185BACKGROUND
Related Links
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Dimana Dimitrova, M.D.
National Cancer Institute (NCI)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 16, 2015
First Posted
October 20, 2015
Study Start
November 19, 2015
Primary Completion (Estimated)
December 31, 2031
Study Completion (Estimated)
December 31, 2036
Last Updated
April 29, 2026
Record last verified: 2026-04-22
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as the database is active.
- Access Criteria
- Clinical data will be made available and with permission of the study PI. Genomic data are made available via dbGAP through requests to the data custodians
All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to dbGAP