GATA2Phase 2NCT05907746
Allogeneic Hematopoietic Stem Cell Transplantation With Briquilimab-Based Conditioning in Participants With GATA2 Deficiency
A Phase 2 study testing Mycophenolate Mofetil, Tacrolimus and Post-Transplant Cyclophosphamide in people with GATA2 and Immunodeficiency, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: People with GATA-binding factor 2 (GATA2) deficiency have a mutation on the GATA2 gene. This gene affects immune function. People with this disease are prone to serious infections; in time, they may develop blood cancers. Read more about this study
- Who is it for?
- Ages 6 to 70 years
- Conditions the study is for
- GATA2, Immunodeficiency
- What is being tested?
- Mycophenolate Mofetil, Tacrolimus and Post-Transplant Cyclophosphamide
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Nov 2023to 31 Jul 2028
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age >= 6 and <= 70 years old
- Germline mutation in the GATA binding protein 2 (GATA2) gene, predicted to be deleterious or previously reported in GATA2 deficiency as determined by targeted GATA2 sequencing performed at the National Institutes of Health (NIH)
- Clinical manifestation(s) consistent with a diagnosis of GATA2 deficiency, including any of the following (Note: only one clinical manifestation is required):
- History of severe, disfiguring, and/or recurrent infections
- Low monocyte (< 190 cells/microL), B cell (< 61 cells/microL) and/or Natural Killer (NK) cell (< 126 cells/microL) counts
- Myelodysplastic syndrome by World Health Organization (WHO) criteria
Show all 22Show fewer
- "Early stage" GATA2 deficiency defined as a hypocellular for age bone marrow with less than 5% blasts and normal cytogenetics or favorable cytogenetics (defined as "good" or "very good" cytogenetics risk groups plus trisomy 8)
- Availability of an 8/8 HLA-matched related or unrelated donor, a 7/8 HLA-matched unrelated donor or a haploidentical related donor
- Lansky (for participants < 16 years of age) or Karnofsky (for participants >=16 years of age) performance status of >= 40%
- Left ventricular ejection fraction > 40%, preferably by 2-D echocardiogram (echo) obtained within 90 days prior to treatment initiation
- Participants must have adequate organ function as defined below:
- Total bilirubin <=2.5 x upper limit of normal (ULN)
- Alanine transaminase (ALT) and aspartate aminotransferase (AST) <= 5 x ULN
- Creatinine:
- Adult participants: <=2.0 mg/dl and creatinine clearance >= 30 ml/min.
- Pediatric participants (<18 years old): creatinine <1.5 mg/dL and a creatinine clearance using the Schwartz Formula > 30 mL/min/1.73m^2
- Pulmonary function tests (PFT)s: Forced expiratory volume in 1 second (FEV1) and adjusted diffusing capacity of the lungs for carbon monoxide (DLCO) >30%. Children who are unable to cooperate for pulmonary function tests (PFTs) due to age are still eligible if no evidence of dyspnea at rest and no need for supplemental oxygen
- Women of childbearing potential (WOCBP) and men must agree to use highly effective contraception (hormonal, intrauterine device (IUD), abstinence, tubal ligation, partner has had the previous vasectomy) at the study entry, for the duration of study treatment, and for at least one-year post-allogeneic HCT or 12 months after completion of chemotherapy preparative administration if HCT is not performed for women and for 4 months for the same for men.
- Breastfeeding participants must be willing to discontinue breastfeeding
- Willingness to remain in the NIH hospital or, if discharged, stay close to the NIH (60 minutes' drive), for a minimum of 100 days after transplant or longer if there are complications. The participants must commit to having an adult caregiver with them during the first 100 days after transplant in case of discharging from the hospital before 100 days verified by social worker
- Participants with hepatitis B virus (HBV) or hepatitis C virus (HCV) antibody-positive testing are allowed if HBV DNA <100 IU/m or HCV RNA level is undetectable. Additionally, transplantation must be approved by a hepatology consult for these participants
- Participants or parents/guardians must be able to understand and willing to sign a written informed consent document
Who cannot join
- Participants with a Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) score >8
- Participants who have received any investigational agents within 4 weeks before treatment initiation with the exception of virus-specific T cells for the treatment of viral infection/reactivation prior to allogeneic HCT
- Participants with a history of hematologic malignancy (e.g., Acute Myeloid Leukemia (AML), Chronic Myelomonocytic Leukemia (CMML). Note: participants with Myelodysplastic Syndromes (MDS) are included
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents (fludarabine, cyclophosphamide, tacrolimus, mycophenolate mofetil, granulocyte-colony stimulating factor (G-CSF)) used in the study
- Presence of active malignancy. Note: participants with malignancy driven by viruses (e.g., human papillomavirus (HPV) or HPV or Epstein-Barr virus (EBV)) are allowed as the immune reconstitution after transplant may control the malignancy and participants with MDS are allowed
- Human immunodeficiency virus (HIV)-infected participants
- Pregnancy (confirmed with Beta-Human Chorionic Gonadotropin (HCG) serum or urine pregnancy test performed in WOCBP at screening)
- Uncontrolled intercurrent illness or social situations (as determined by social work consult) that would limit compliance with study requirements
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: A Phase II Study of Allogeneic Hematopoietic Stem Cell Transplantation With Briquilimab-Based Conditioning in Participants With GATA2 Deficiency
Background:
People with GATA-binding factor 2 (GATA2) deficiency have a mutation on the GATA2 gene. This gene affects immune function. People with this disease are prone to serious infections; in time, they may develop blood cancers. A hematopoietic stem cell (HSC) transplant can cure GATA2 deficiency, but using stem cells donated by other people can cause serious side effects.
Read more
Objective:
To test a new drug (Briquilimab) to see if it can make HSC transplants safer.
Eligibility:
People aged 6 to 70 years who have GATA2 deficiency.
Design:
Participants will be screened. They will have a physical exam, with blood and urine tests. They will have tests of their heart and lung function. They may have a bone marrow biopsy: Their hip will be numbed; a large needle will be inserted to draw out tissue from inside the pelvis.
Participants will have a central venous catheter placed in a vein of the neck or chest. This will be used to draw blood and administer drugs.
Briquilimab will be given through the catheter about 11 days before the transplant. This is part of conditioning: preparing the body to receive the new stem cells. Conditioning also includes other medications and total body irradiation.
Donor stem cells will be administered through the catheter. Participants will receive other approved drugs to help prevent side effects.
Participants will stay in the hospital from the beginning of the conditioning until several weeks after the transplant. They will remain in the local area for 100 days after discharge; they will come to the clinic at least once a week during this time. Follow-up visits will continue for 3 years....
Read the detailed description
Background:
- GATA-binding factor 2 (GATA2) deficiency, an immunodeficiency and bone marrow failure disorder due to inherited or sporadic mutations in or loss of one allele of the GATA2 gene, is characterized by: 1) nontuberculous mycobacteria (NTM) and other opportunistic infections, 2) deficiency of monocytes, B lymphocytes, and Natural Killer (NK) cells in the peripheral blood, and 3) progression to myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), and acute myelogenous leukemia (AML).
- Allogeneic hematopoietic cell transplantation (HCT) appears to be curative, and interim results from protocol #13-C-0132, NCT01861106, demonstrated a 2-year event-free survival rate of 83% for 59 participants with GATA2 deficiency who underwent HCT with a busulfan-based conditioning regimen.
- However, traditional HCT approaches using alkylating agents such as busulfan continue to place recipients at risk for potentially life-threatening, transplant-related toxicities as well as late effects such as infertility and secondary malignancy.
- Briquilimab is a humanized, glycosylated immunoglobulin G1 (IgG1) monoclonal antibody that targets CD117 (human c-Kit) present on endogenous hematopoietic stem cells (HSC). Briquilimab has been shown in pre-clinical and early clinical studies to safely deplete human and non-human primate HSC with minimal toxicity.
Primary Objective:
-To determine whether allogeneic hematopoietic cell transplantation with Briquilimab-based conditioning results in sustained donor engraftment by 100 days post-transplant in participants with GATA2 deficiency
Eligibility:
- Recipients aged 6-70 years old with pathogenic germline mutations in GATA2 and clinical manifestations consistent with a diagnosis of GATA2 deficiency
- Have an 8/8 Human leukocyte antigen (HLA)-matched related or unrelated donor or a 7/8 HLA-matched unrelated donor or haploidentical related donor
- Have "early stage" GATA2 deficiency defined as a hypocellular for age bone marrow with less than 5% blasts and normal or favorable cytogenetics (defined as "good" or "very good" cytogenetics risk groups plus trisomy 8)
Design:
- All participants with GATA2 deficiency will receive a pre-transplant conditioning regimen consisting of Briquilimab administered as a single intravenous (IV) infusion on day -11 (range day -13 to -10) with pharmacokinetics, followed by fludarabine or fludarabine/cyclophosphamide IV infusions (3 or 5 days depending on the donor) and 200 cGy total body irradiation (TBI) on day -1. HCT will be infused on day 0.
- Participants with an 8/8 human leukocyte antigen (HLA)-matched related or unrelated donor assigned to Arm A will receive a fludarabine for three days on days -4, -3, and -2.
- Participants with a 7/8 HLA-matched unrelated donor or a haploidentical related donor assigned to Arm B will receive a fludarabine for five days on days -6, -5, -4, -3, and -2, cyclophosphamide for 2 days on days -6 and -5
- Post-transplant immunosuppression for Graft Versus Host Disease (GVHD) prophylaxis for recipients of Arms A and B will consist of cyclophosphamide for 2 days on days +3 and +4, along with mycophenolate mofetil from day +5 to approximately day +35 and tacrolimus from day +5 to approximately day +180. If there is no evidence of GVHD, tacrolimus will be stopped or tapered at approximately day +180
- Conditions
- GATA2, Immunodeficiency
- Being tested
- Mycophenolate Mofetil, Tacrolimus, Post-Transplant Cyclophosphamide, Total Body Irradiation, Hematopoietic Cell Transplant
- Keywords
- Immunodeficiency, Hematopoietic Cell Transplant, Haploidentical
- Medical subject headings
- Immunologic Deficiency Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called CellCept, Myhibbin
15 mg/kg intravenous (IV) three times per day starting on day +5 until approximately day +30 (+/- 2 days)
TacrolimusDrug
Also called Prograf
0.02 mg/kg intravenous (IV) daily starting on day +5
Post-Transplant CyclophosphamideDrug
Also called Post-Transplant Cytoxan, Post-Transplant Neosar
50 mg/kg intravenous (IV) daily on days +3 and +4
Total Body IrradiationRadiation
Also called TBI
200 centigray (cGy) on day -1
Hematopoietic Cell TransplantProcedure or surgery
Also called HCT
Stem cell transplant on day 0
BriquilimabDrug
Also called JSP191
Single 0.6 mg/kg intravenous (IV) infusion administered between days -13 and day -10
CyclophosphamideDrug
Also called Cytoxan, Neosar
14.5 mg/kg intravenous (IV) daily on days -6 and -5; for 7/8 Unrelated or Haploidentical Donor, prior to transplant.
FludarabineDrug
Also called Fludara
30 mg/m^2 intravenous (IV) over 30 minutes daily. For 8/8 Matched Related or Unrelated Donor, fludarabine dose will be on days -4, -3, and -2. For 7/8 Unrelated or Haploidentical Donor, fludarabine dose will be on days -6, -5, -4, -3, and -2.
Bone Marrow BiopsyProcedure or surgery
Also called BM Bx
Screening ≤90 days.
Bone Marrow AspirateProcedure or surgery
Also called BM aspirate
Screening ≤90 days.
2D echoDiagnostic test
Also called Two-dimensional echocardiogram
Screening ≤90 days.
EKGDiagnostic test
Also called Electrocardiogram
Screening ≤90 days.
PFT'sProcedure or surgery
Also called Pulmonary function tests
Screening ≤90 days.
CT scan of chest, abdomen and pelvisDiagnostic test
Also called Computed tomography of chest, abdomen and pelvis
Baseline ≤28 days.
| Study group | Role | What they receive |
|---|---|---|
| Arm A -Briquilimab, Fludarabine, 200 centigray (cGy) Total Body Irradiation | Experimental | Briquilimab, Fludarabine, Total Body Irradiation Receives: Drug: Mycophenolate Mofetil; Drug: Tacrolimus; Drug: Post-Transplant Cyclophosphamide; Radiation: Total Body Irradiation; Procedure: Hematopoietic Cell Transplant; Drug: Briquilimab; Drug: Fludarabine; Procedure: Bone Marrow Biopsy; Procedure: Bone Marrow Aspirate; Diagnostic Test: 2D echo; Diagnostic Test: EKG; Procedure: PFT's; Diagnostic Test: CT scan of chest, abdomen and pelvis |
| Arm B - Briquilimab, Fludarabine, Cyclophosphamide, 200 centigray (cGy) Total Body Irradiation | Experimental | Briquilimab, Fludarabine, Cyclophosphamide, Total Body Irradiation Receives: Drug: Mycophenolate Mofetil; Drug: Tacrolimus; Drug: Post-Transplant Cyclophosphamide; Radiation: Total Body Irradiation; Procedure: Hematopoietic Cell Transplant; Drug: Briquilimab; Drug: Cyclophosphamide; Drug: Fludarabine; Procedure: Bone Marrow Biopsy; Procedure: Bone Marrow Aspirate; Diagnostic Test: 2D echo; Diagnostic Test: EKG; Procedure: PFT's; Diagnostic Test: CT scan of chest, abdomen and pelvis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Evaluable Participants With GATA-binding Factor 2 (GATA2) Deficiency With Sustained Donor Engraftment by 100 Days Post-transplant Reported Along With a Two-sided 90% Confidence Interval
To determine whether allogeneic hematopoietic cell transplantation with Briquilimab-based conditioning results in sustained donor engraftment by 100 days post-transplant, the percentage of evaluable participants with GATA2 deficiency will be reported along with a two-sided 90% confidence interval. Sustained donor engraftment is defined as neutrophil recovery with ANC ≥ 500/mm^3 for 3 consecutive days associated with >90% myeloid and >10% cluster of differentiation 3 (CD3+) T cell donor chimerism by 100 days post-transplant.
Measured: 100 days
Percentage of Evaluable Participants With GATA-binding Factor 2 (GATA2) Deficiency With Sustained Donor Engraftment by 100 Days Post-transplant Reported Along With a Two-sided 95% Confidence Interval
To determine whether allogeneic hematopoietic cell transplantation with Briquilimab-based conditioning results in sustained donor engraftment by 100 days post-transplant, the percentage of evaluable participants with GATA2 deficiency will be reported along with a two-sided 95% confidence interval. Sustained donor engraftment is defined as neutrophil recovery with ANC ≥ 500/mm^3 for 3 consecutive days associated with >90% myeloid and >10% cluster of differentiation 3 (CD3+) T cell donor chimerism by 100 days post-transplant and restoration of normal hematopoiesis by one-year post-transplant.
Measured: 100 days
Secondary outcomes (7)
Percentage of Evaluated Participants With GATA-binding Factor 2 (GATA2) Deficiency Who Received Allogeneic Hematopoietic Cell Transplantation With Briquilimab-based Conditioning That Results in Restoration of Normal Hematopoiesis by 1-year Post-transplant
To determine whether allogeneic hematopoietic cell transplantation with Briquilimab-based conditioning results in restoration of normal hematopoiesis by one-year post-transplant in participants with GATA2 deficiency the percentage of evaluated participants will be reported along with a 95% two-sided confidence interval. Restoration of normal hematopoiesis is defined as normalization of peripheral blood counts hemoglobin (Hb) >8 g/dL, platelet count > 100,000/µ/L and absolute neutrophil count (ANC)>1,500/µ/L).
Measured: 1-year
Number of Participants With GATA2 Deficiency Conditioned With Briquilimab With Transplant-related Toxicity Reported by Type and Grade of Adverse Event by Arm
By Arm, the participants with transplant-related toxicity will be reported by type and grade of event. Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 1 is mild. Grade 2 is moderate. Grade 3 is serious. Grade 4 is life-threatening. Grade 5 is death related to adverse event.
Measured: 3 years
3-year Overall Survival (OS)
OS is defined as time from treatment start date until death from any cause, last follow up or date last known alive. OS was determined by using the Kaplan-Meier method and is reported along with the median value and the 95% confidence interval.
Measured: 3 years
3-year Event-free Survival (EFS)
EFS is defined as death, receipt of a second transplant, or graft failure. EFS was determined using the Kaplan-Meier method and is reported along with the median value and the 95% confidence interval. Primary graft failure is defined as the lack of donor-derived neutrophil engraftment by day +60 after transplant. Secondary graft failure is defined as initial donor-derived neutrophil engraftment followed by the subsequent loss of donor chimerism to < 10% donor whole blood or myeloid peripheral blood chimerism.
Measured: 3 years
Percentage of Participants With Secondary Graft Failure Within 3 Years After Transplant
Percentage of participants with secondary graft failure at 3 years is reported separately by cohort along with 95% two-sided confidence interval. Secondary graft failure is defined as initial donor-derived neutrophil engraftment followed by the subsequent loss of donor chimerism to < 10% donor whole blood or myeloid peripheral blood chimerism within 3 years after transplant.
Measured: 3 years
Incidence of Grades III-IV Acute and Moderate to Severe Chronic Graft Versus Host Disease (GVHD)
Incidence of grades III-IV acute and moderate to severe chronic graft versus host disease within 3 years after transplant will be reported separately by cohort using simple estimates along with 95% two-sided confidence intervals. In addition, cumulative incidence curves along with 95% two-sided confidence interval. Acute GVHD staging and grading will be assessed according to the 1994 Consensus Conference on Acute GVHD Grading criteria. Grade III liver (bilirubin) stage 2-3 or stage 2.4 gut (stool output per day). Grade IV is stage 4 (skin) or stage 4 liver (bilirubin). Chronic GVHD diagnosis and staging will be assessed according to the 2014 Chronic GVHD Consensus Project. Diagnostic signs and symptoms of chronic GVHD are those that establish the diagnosis of chronic GVHD without need for further testing or evidence of other organ involvement.
Measured: Day 100 (Acute GVHD) and 1-, 2-, and 3-year post-transplant (Chronic GVHD)
Cumulative Incidence of Transplant-related Mortality Reported Along With a 95% Two-sided Confidence Interval
Cumulative incidence curves accounting for the competing risk of transplant-related mortality will be constructed by cohort, with the values reported at day 100, one, and two years, along with a 95% two-sided confidence interval.
Measured: Day 100, 1 year and 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2023
- Study start29 Nov 2023
- Primary completion16 Oct 2025
- Study completion31 Jul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for GATA2Studies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Danielle Pregent-Arnold, National Cancer Institute (NCI)
- Investigators
- Danielle E Pregent-Arnold, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05907746
- Sponsor's protocol ID
- 10001531
- Other IDs
- 001531-C
- Status last verified
- Aug 2026
- First submitted
- 15 Jun 2023
- Last updated
- 11 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Allogeneic Hematopoietic Stem Cell Transplantation With Briquilimab-Based Conditioning in Participants With GATA2 Deficiency
- ClinicalTrials.gov ID
- NCT05907746
- Acronym / sponsor ID
- 10001531
- Conditions
- GATA2, Immunodeficiency
- Keywords
- Immunodeficiency, Hematopoietic Cell Transplant, Haploidentical
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 13 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 29 Nov 2023 (actual)
- Primary completion
- 16 Oct 2025 (actual)
- Study completion
- 31 Jul 2028 (estimated)
- First posted
- 18 Jun 2023 (actual)
- Results
- Posted 29 May 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
People with GATA-binding factor 2 (GATA2) deficiency have a mutation on the GATA2 gene. This gene affects immune function. People with this disease are prone to serious infections; in time, they may develop blood cancers. A hematopoietic stem cell (HSC) transplant can cure GATA2 deficiency, but using stem cells donated by other people can cause serious side effects.
Objective:
To test a new drug (Briquilimab) to see if it can make HSC transplants safer.
Eligibility:
People aged 6 to 70 years who have GATA2 deficiency.
Design:
Participants will be screened. They will have a physical exam, with blood and urine tests. They will have tests of their heart and lung function. They may have a bone marrow biopsy: Their hip will be numbed; a large needle will be inserted to draw out tissue from inside the pelvis.
Participants will have a central venous catheter placed in a vein of the neck or chest. This will be used to draw blood and administer drugs.
Briquilimab will be given through the catheter about 11 days before the transplant. This is part of conditioning: preparing the body to receive the new stem cells. Conditioning also includes other medications and total body irradiation.
Donor stem cells will be administered through the catheter. Participants will receive other approved drugs to help prevent side effects.
Participants will stay in the hospital from the beginning of the conditioning until several weeks after the transplant. They will remain in the local area for 100 days after discharge; they will come to the clinic at least once a week during this time. Follow-up visits will continue for 3 years....
Detailed description
Background:
- GATA-binding factor 2 (GATA2) deficiency, an immunodeficiency and bone marrow failure disorder due to inherited or sporadic mutations in or loss of one allele of the GATA2 gene, is characterized by: 1) nontuberculous mycobacteria (NTM) and other opportunistic infections, 2) deficiency of monocytes, B lymphocytes, and Natural Killer (NK) cells in the peripheral blood, and 3) progression to myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), and acute myelogenous leukemia (AML).
- Allogeneic hematopoietic cell transplantation (HCT) appears to be curative, and interim results from protocol #13-C-0132, NCT01861106, demonstrated a 2-year event-free survival rate of 83% for 59 participants with GATA2 deficiency who underwent HCT with a busulfan-based conditioning regimen.
- However, traditional HCT approaches using alkylating agents such as busulfan continue to place recipients at risk for potentially life-threatening, transplant-related toxicities as well as late effects such as infertility and secondary malignancy.
- Briquilimab is a humanized, glycosylated immunoglobulin G1 (IgG1) monoclonal antibody that targets CD117 (human c-Kit) present on endogenous hematopoietic stem cells (HSC). Briquilimab has been shown in pre-clinical and early clinical studies to safely deplete human and non-human primate HSC with minimal toxicity.
Primary Objective:
-To determine whether allogeneic hematopoietic cell transplantation with Briquilimab-based conditioning results in sustained donor engraftment by 100 days post-transplant in participants with GATA2 deficiency
Eligibility:
- Recipients aged 6-70 years old with pathogenic germline mutations in GATA2 and clinical manifestations consistent with a diagnosis of GATA2 deficiency
- Have an 8/8 Human leukocyte antigen (HLA)-matched related or unrelated donor or a 7/8 HLA-matched unrelated donor or haploidentical related donor
- Have "early stage" GATA2 deficiency defined as a hypocellular for age bone marrow with less than 5% blasts and normal or favorable cytogenetics (defined as "good" or "very good" cytogenetics risk groups plus trisomy 8)
Design:
- All participants with GATA2 deficiency will receive a pre-transplant conditioning regimen consisting of Briquilimab administered as a single intravenous (IV) infusion on day -11 (range day -13 to -10) with pharmacokinetics, followed by fludarabine or fludarabine/cyclophosphamide IV infusions (3 or 5 days depending on the donor) and 200 cGy total body irradiation (TBI) on day -1. HCT will be infused on day 0.
- Participants with an 8/8 human leukocyte antigen (HLA)-matched related or unrelated donor assigned to Arm A will receive a fludarabine for three days on days -4, -3, and -2.
- Participants with a 7/8 HLA-matched unrelated donor or a haploidentical related donor assigned to Arm B will receive a fludarabine for five days on days -6, -5, -4, -3, and -2, cyclophosphamide for 2 days on days -6 and -5
- Post-transplant immunosuppression for Graft Versus Host Disease (GVHD) prophylaxis for recipients of Arms A and B will consist of cyclophosphamide for 2 days on days +3 and +4, along with mycophenolate mofetil from day +5 to approximately day +35 and tacrolimus from day +5 to approximately day +180. If there is no evidence of GVHD, tacrolimus will be stopped or tapered at approximately day +180
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A -Briquilimab, Fludarabine, 200 centigray (cGy) Total Body Irradiation | Experimental | Drug: Mycophenolate Mofetil, Drug: Tacrolimus, Drug: Post-Transplant Cyclophosphamide, Radiation: Total Body Irradiation, Procedure: Hematopoietic Cell Transplant, Drug: Briquilimab, Drug: Fludarabine, Procedure: Bone Marrow Biopsy, Procedure: Bone Marrow Aspirate, Diagnostic Test: 2D echo, Diagnostic Test: EKG, Procedure: PFT's, Diagnostic Test: CT scan of chest, abdomen and pelvisBriquilimab, Fludarabine, Total Body Irradiation |
| Arm B - Briquilimab, Fludarabine, Cyclophosphamide, 200 centigray (cGy) Total Body Irradiation | Experimental | Drug: Mycophenolate Mofetil, Drug: Tacrolimus, Drug: Post-Transplant Cyclophosphamide, Radiation: Total Body Irradiation, Procedure: Hematopoietic Cell Transplant, Drug: Briquilimab, Drug: Cyclophosphamide, Drug: Fludarabine, Procedure: Bone Marrow Biopsy, Procedure: Bone Marrow Aspirate, Diagnostic Test: 2D echo, Diagnostic Test: EKG, Procedure: PFT's, Diagnostic Test: CT scan of chest, abdomen and pelvisBriquilimab, Fludarabine, Cyclophosphamide, Total Body Irradiation |
Who may qualify
- Ages
- 6 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (22 listed)
- Age >= 6 and <= 70 years old
- Germline mutation in the GATA binding protein 2 (GATA2) gene, predicted to be deleterious or previously reported in GATA2 deficiency as determined by targeted GATA2 sequencing performed at the National Institutes of Health (NIH)
- Clinical manifestation(s) consistent with a diagnosis of GATA2 deficiency, including any of the following (Note: only one clinical manifestation is required):
- "Early stage" GATA2 deficiency defined as a hypocellular for age bone marrow with less than 5% blasts and normal cytogenetics or favorable cytogenetics (defined as "good" or "very good" cytogenetics risk groups plus trisomy 8)
- Availability of an 8/8 HLA-matched related or unrelated donor, a 7/8 HLA-matched unrelated donor or a haploidentical related donor
Key exclusion criteria (8 listed)
- Participants with a Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) score >8
- Participants who have received any investigational agents within 4 weeks before treatment initiation with the exception of virus-specific T cells for the treatment of viral infection/reactivation prior to allogeneic HCT
- Participants with a history of hematologic malignancy (e.g., Acute Myeloid Leukemia (AML), Chronic Myelomonocytic Leukemia (CMML). Note: participants with Myelodysplastic Syndromes (MDS) are included
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents (fludarabine, cyclophosphamide, tacrolimus, mycophenolate mofetil, granulocyte-colony stimulating factor (G-CSF)) used in the study
- Presence of active malignancy. Note: participants with malignancy driven by viruses (e.g., human papillomavirus (HPV) or HPV or Epstein-Barr virus (EBV)) are allowed as the immune reconstitution after transplant may control the malignancy and participants with MDS are allowed
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mycophenolate MofetilAlso: CellCept, Myhibbin15 mg/kg intravenous (IV) three times per day starting on day +5 until approximately day +30 (+/- 2 days) | Drug | Arm A -Briquilimab, Fludarabine, 200 centigray (cGy) Total Body Irradiation, Arm B - Briquilimab, Fludarabine, Cyclophosphamide, 200 centigray (cGy) Total Body Irradiation |
| TacrolimusAlso: Prograf0.02 mg/kg intravenous (IV) daily starting on day +5 | Drug | Arm A -Briquilimab, Fludarabine, 200 centigray (cGy) Total Body Irradiation, Arm B - Briquilimab, Fludarabine, Cyclophosphamide, 200 centigray (cGy) Total Body Irradiation |
| Post-Transplant CyclophosphamideAlso: Post-Transplant Cytoxan, Post-Transplant Neosar50 mg/kg intravenous (IV) daily on days +3 and +4 | Drug | Arm A -Briquilimab, Fludarabine, 200 centigray (cGy) Total Body Irradiation, Arm B - Briquilimab, Fludarabine, Cyclophosphamide, 200 centigray (cGy) Total Body Irradiation |
| Total Body IrradiationAlso: TBI200 centigray (cGy) on day -1 | Radiation | Arm A -Briquilimab, Fludarabine, 200 centigray (cGy) Total Body Irradiation, Arm B - Briquilimab, Fludarabine, Cyclophosphamide, 200 centigray (cGy) Total Body Irradiation |
| Hematopoietic Cell TransplantAlso: HCTStem cell transplant on day 0 | Procedure or surgery | Arm A -Briquilimab, Fludarabine, 200 centigray (cGy) Total Body Irradiation, Arm B - Briquilimab, Fludarabine, Cyclophosphamide, 200 centigray (cGy) Total Body Irradiation |
| BriquilimabAlso: JSP191Single 0.6 mg/kg intravenous (IV) infusion administered between days -13 and day -10 | Drug | Arm A -Briquilimab, Fludarabine, 200 centigray (cGy) Total Body Irradiation, Arm B - Briquilimab, Fludarabine, Cyclophosphamide, 200 centigray (cGy) Total Body Irradiation |
| CyclophosphamideAlso: Cytoxan, Neosar14.5 mg/kg intravenous (IV) daily on days -6 and -5; for 7/8 Unrelated or Haploidentical Donor, prior to transplant. | Drug | Arm B - Briquilimab, Fludarabine, Cyclophosphamide, 200 centigray (cGy) Total Body Irradiation |
| FludarabineAlso: Fludara30 mg/m^2 intravenous (IV) over 30 minutes daily. For 8/8 Matched Related or Unrelated Donor, fludarabine dose will be on days -4, -3, and -2. For 7/8 Unrelated or Haploidentical Donor, fludarabine dose will be on days -6, -5, -4, -3, and -2. | Drug | Arm A -Briquilimab, Fludarabine, 200 centigray (cGy) Total Body Irradiation, Arm B - Briquilimab, Fludarabine, Cyclophosphamide, 200 centigray (cGy) Total Body Irradiation |
| Bone Marrow BiopsyAlso: BM BxScreening ≤90 days. | Procedure or surgery | Arm A -Briquilimab, Fludarabine, 200 centigray (cGy) Total Body Irradiation, Arm B - Briquilimab, Fludarabine, Cyclophosphamide, 200 centigray (cGy) Total Body Irradiation |
| Bone Marrow AspirateAlso: BM aspirateScreening ≤90 days. | Procedure or surgery | Arm A -Briquilimab, Fludarabine, 200 centigray (cGy) Total Body Irradiation, Arm B - Briquilimab, Fludarabine, Cyclophosphamide, 200 centigray (cGy) Total Body Irradiation |
| 2D echoAlso: Two-dimensional echocardiogramScreening ≤90 days. | Diagnostic test | Arm A -Briquilimab, Fludarabine, 200 centigray (cGy) Total Body Irradiation, Arm B - Briquilimab, Fludarabine, Cyclophosphamide, 200 centigray (cGy) Total Body Irradiation |
| EKGAlso: ElectrocardiogramScreening ≤90 days. | Diagnostic test | Arm A -Briquilimab, Fludarabine, 200 centigray (cGy) Total Body Irradiation, Arm B - Briquilimab, Fludarabine, Cyclophosphamide, 200 centigray (cGy) Total Body Irradiation |
| PFT'sAlso: Pulmonary function testsScreening ≤90 days. | Procedure or surgery | Arm A -Briquilimab, Fludarabine, 200 centigray (cGy) Total Body Irradiation, Arm B - Briquilimab, Fludarabine, Cyclophosphamide, 200 centigray (cGy) Total Body Irradiation |
| CT scan of chest, abdomen and pelvisAlso: Computed tomography of chest, abdomen and pelvisBaseline ≤28 days. | Diagnostic test | Arm A -Briquilimab, Fludarabine, 200 centigray (cGy) Total Body Irradiation, Arm B - Briquilimab, Fludarabine, Cyclophosphamide, 200 centigray (cGy) Total Body Irradiation |
Primary outcome
Percentage of Evaluable Participants With GATA-binding Factor 2 (GATA2) Deficiency With Sustained Donor Engraftment by 100 Days Post-transplant Reported Along With a Two-sided 90% Confidence Interval
Time frame: 100 days
To determine whether allogeneic hematopoietic cell transplantation with Briquilimab-based conditioning results in sustained donor engraftment by 100 days post-transplant, the percentage of evaluable participants with GATA2 deficiency will be reported along with a two-sided 90% confidence interval. Sustained donor engraftment is defined as neutrophil recovery with ANC ≥ 500/mm^3 for 3 consecutive days associated with >90% myeloid and >10% cluster of differentiation 3 (CD3+) T cell donor chimerism by 100 days post-transplant.
Percentage of Evaluable Participants With GATA-binding Factor 2 (GATA2) Deficiency With Sustained Donor Engraftment by 100 Days Post-transplant Reported Along With a Two-sided 95% Confidence Interval
Time frame: 100 days
To determine whether allogeneic hematopoietic cell transplantation with Briquilimab-based conditioning results in sustained donor engraftment by 100 days post-transplant, the percentage of evaluable participants with GATA2 deficiency will be reported along with a two-sided 95% confidence interval. Sustained donor engraftment is defined as neutrophil recovery with ANC ≥ 500/mm^3 for 3 consecutive days associated with >90% myeloid and >10% cluster of differentiation 3 (CD3+) T cell donor chimerism by 100 days post-transplant and restoration of normal hematopoiesis by one-year post-transplant.
7 secondary outcomes
Percentage of Evaluated Participants With GATA-binding Factor 2 (GATA2) Deficiency Who Received Allogeneic Hematopoietic Cell Transplantation With Briquilimab-based Conditioning That Results in Restoration of Normal Hematopoiesis by 1-year Post-transplant
Time frame: 1-year
Number of Participants With GATA2 Deficiency Conditioned With Briquilimab With Transplant-related Toxicity Reported by Type and Grade of Adverse Event by Arm
Time frame: 3 years
3-year Overall Survival (OS)
Time frame: 3 years
3-year Event-free Survival (EFS)
Time frame: 3 years
Percentage of Participants With Secondary Graft Failure Within 3 Years After Transplant
Time frame: 3 years
Incidence of Grades III-IV Acute and Moderate to Severe Chronic Graft Versus Host Disease (GVHD)
Time frame: Day 100 (Acute GVHD) and 1-, 2-, and 3-year post-transplant (Chronic GVHD)
Cumulative Incidence of Transplant-related Mortality Reported Along With a 95% Two-sided Confidence Interval
Time frame: Day 100, 1 year and 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Danielle E Pregent-Arnold, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Mycophenolate Mofetil, Tacrolimus and Post-Transplant Cyclophosphamide in people with GATA2 and Immunodeficiency, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 11 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 May 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Evaluable Participants With GATA-binding Factor 2 (GATA2) Deficiency With Sustained Donor Engraftment by 100 Days Post-transplant Reported Along With a Two-sided 90% Confidence Interval (time frame: 100 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2026.