Regenerative Medicine for Immune Deficiencies and Bone Marrow Failures
This study is looking at a new way to perform bone marrow transplants (hematopoietic stem cell transplant or HSCT) for people with certain immune system problems (primary immune deficiencies, immune dysregulatory syndromes) and inherited bone marrow failures, including Fanconi anemia. The goal is to see if a specific transplant approach, using a reduced intensity conditioning (RIC) regimen with drugs like Alemtuzumab, Fludarabine, Melphalan, and low-dose total body irradiation, followed by Cyclophosphamide after the transplant, can help the donor cells successfully grow (engraftment). Researchers will measure engraftment at 60 days after the transplant. This study is open to individuals aged 4 months to 50 years. The study aims to enroll 27 participants, but its current status is unclear.
- Study design
- This is a Phase 2 interventional study, meaning all participants will receive the study treatment. It aims to enroll 27 participants.
- What's involved
- Not specified in the trial record.
- Compensation
- Not stated in the trial record.
- Follow-up
- The primary outcome, donor engraftment, will be measured at 60 days after the transplant.
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NCT04232085
Regenerative Medicine to Restore Hematopoiesis and Immune Function in Immunodeficiencies and Inherited Bone Marrow Failures
Recruiting
PHASE2Ages 4–50InterventionalTreatmentSidney Kimmel Comprehensive Cancer Center at Johns HopkinsInvestigator-initiated
~27 participants
Updated 2025-11-28 on ClinicalTrials.gov
What's tested:AlemtuzumabFludarabineMelphalanLow Dose Total Body IrradiationCyclophosphamideTacrolimus
At a glance
Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Donor Engraftment
Measured over 60 Days
Conditions
Where it's being run
1 sites across 1 statesMaryland1
Study leadership
- Heather J Symons, MD, MHS · PRINCIPAL_INVESTIGATOR · Johns Hopkins University
Who to contact
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Do you actually qualify for this trial?
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Eligibility criteria
Inclusion
Chronic granulomatous disease (CGD)
Wiskott-Aldrich syndrome (WAS)
Hyper-IgM syndrome
Common variable immunodeficiency (CVID)
Leukocyte adhesion deficiency-1 (LAD-1)
Severe Combined Immunodeficiency (SCID)
CTLA-4 deficiency
CARD9 deficiency
DOCK8 deficiency
Immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome
Hemophagocytic lymphohistiocytosis (HLH) or related disorder with indication for transplant
CAEBV: Patients with chronic EBV infection (CAEBV) with indication for BMT:
Congenital amegakaryocytic thrombocytopenia (CAMT)
Diamond Blackfan anemia (DBA)
Shwachman Diamond Syndrome (SDS)
Thrombocytopenia Absent Radii (TAR)
Glanzmans thrombasthenia (GT)
Kostmann syndrome
Other indications and/or other PID, IDS, and IBMFS diagnoses as deemed appropriate by the PI.
Fanconi anemia
Non-Fanconi DNA-dsb repair disorders
Cerunnos-XRCC4-like factor deficiency (XLF or NHEJ1)
DNA ligase IV deficiency (LIG4)
Nijmegen breakage syndrome (NBS)
Increased DNA breakage after exposure of patient cells to DNA cross-linking agents such as diepoxybutane or mitomycin C and germline mutation(s) in an identified Fanconi pathway gene.
Fully HLA matched sibling or other first-degree family member.
Fully HLA matched unrelated 10/10 donor using high-resolution DNA-based typing at the following genetic loci: HLA-A, -B, -C, DRB1, and DQB1.
Mismatched unrelated donor at 8 or 9/10 alleles, using high-resolution typing as above.
HLA-haploidentical family members of any degree who match at least one allele of each of the following genetic loci: HLA-A, -B, -C, DRB1, and DQB1. A minimum match of 5/10 is therefore required, and will be considered sufficient evidence that the donor and recipient share one HLA haplotype.
The patient and/or legal guardian must sign informed consent for BMT.
Patients with adequate organ function as measured by
Cardiac: Left ventricular ejection fraction (LVEF) at rest must be ≥ 35%. For patients aged \<13 years, shortening fraction (SF) \> 25% by echocardiogram or LVEF by MUGA may be used.
Hepatic: Bilirubin ≤ 3.0 mg/dL; and ALT, AST, and Alkaline Phosphatase \< 5 x ULN.
Renal: Serum creatinine within normal range for age, or if serum creatinine outside normal range for age, then renal function (creatinine clearance or GFR) \> 40 mL/min/1.73m2.
Pulmonary: PFT with FEV1 and FVC \>/= 50% of normal and DLCO corrected for Hgb \>/= 40% of normal. Patients unable to undergo PFTs should have stable resp status with SaO2 \>90% on a max of 2L/min supplemental O2.
Karnofsky or Lansky performance status ≥70%
Females and males of childbearing potential must agree to practice 2 effective methods of contraception at the same time, or agree to abstinence.
Exclusion
Patients will not be excluded on the basis of sex, racial or ethnic background.
Positive leukocytotoxic crossmatch.
Prior allogeneic stem cell transplant.
Uncontrolled bacterial, viral, or fungal infection at the time of enrollment. Uncontrolled is defined as currently taking medication and with progression or no clinical improvement on adequate medical treatment. The investigators recognize that patients with CAEBV may have ongoing EBV viremia at the time of initiating pre-transplant therapy, but other patients should have no uncontrolled bacterial, viral, or fungal infections.
Diagnosis of idiopathic aplastic anemia
Seropositivity for the human immunodeficiency virus (HIV)
Active Hepatitis B or C determined by serology and/or NAT
Female patients who are diagnosed as pregnant by beta bHCG testing (per institutional practice) or who are breast-feeding.
Active malignancy or within the timeframe for significant concern for relapse of prior malignancy
For Cohort B and C: liver biopsy (if performed, not required) with moderate-severe fibrosis/cirrhosis
Donor must be medically, socially, and psychologically fit to donate
Bone marrow is the preferred graft source, however, PBSCs may be requested. In particular, PBSCs may be preferred for patients with active viral reactivations and/or for patients who would benefit from a higher count in the graft. Cord blood is not permitted.
First-degree relatives should be tested for degree of HLA match, CMV serology, ABO type, and complete blood count (CBC). An unrelated donor search should be initiated at the time the patient is referred for BMT.
Age ≥5 years
Donors must meet the selection criteria as defined by the Foundation for the Accreditation of Hematopoietic Cell Therapy (FACT).
Lack of recipient anti-donor HLA antibody in recipient
Note: In some instances, low level, non-cytotoxic HLA specific antibodies may be permissible if found to be at a level well below that detectable by flow cytometry. This will be decided on a case-by-case basis by the PI and one of the immunogenetics directors.
In inherited disorders, family members must be tested for carrier and disease status of the underlying disorders. In the event that family members are unaffected carriers, eligibility as donors will be decided upon by the PI on a case-by-case basis
In the event that two or more eligible donors are identified, the donor will be selected per institutional standards. Suggested criteria include the following:
Related is preferred over unrelated.
The potential donor that is youngest in age is preferred.
For CMV seronegative patients, a CMV seronegative donor is preferred. For CMV seropositive patients, a CMV seropositive donor is preferred.
Red blood cell compatibility, in order of preference:
RBC cross match compatible Minor ABO incompatibility, Major ABO incompatibility
If the patient is male, male donors are preferred.
What this trial measures
- Donor Engraftment60 Days
Rate of donor engraftment ≥95% at day 60 as measured by donor chimerism in whole blood.