Allogeneic Hematopoietic Stem Cell Transplantation With Briquilimab-Based Conditioning in Participants With GATA2 Deficiency

NCT05907746 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 2 other identifiers: 10001531001531-C
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief 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. 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....

Conditions

GATA2; Immunodeficiency

Keywords

Immunodeficiency; Hematopoietic Cell Transplant; Haploidentical

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  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

  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

  3 years

• 3-year Overall Survival (OS)

  3 years

• 3-year Event-free Survival (EFS)

  3 years

• Percentage of Participants With Secondary Graft Failure Within 3 Years After Transplant

  3 years

Other Outcomes (1)

• Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

  Adverse Events were monitored/assessed from the first study intervention through resolution of event through study completion, up to 2 years

Study Arms (2)

Arm A -Briquilimab, Fludarabine, 200 centigray (cGy) Total Body Irradiation

EXPERIMENTAL

Briquilimab, Fludarabine, Total Body Irradiation

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

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

Interventions

Mycophenolate Mofetil DRUG

15 mg/kg intravenous (IV) three times per day starting on day +5 until approximately day +30 (+/- 2 days)

Also known as: CellCept, Myhibbin

Arm A -Briquilimab, Fludarabine, 200 centigray (cGy) Total Body Irradiation; Arm B - Briquilimab, Fludarabine, Cyclophosphamide, 200 centigray (cGy) Total Body Irradiation

Tacrolimus DRUG

0.02 mg/kg intravenous (IV) daily starting on day +5

Also known as: Prograf

Arm A -Briquilimab, Fludarabine, 200 centigray (cGy) Total Body Irradiation; Arm B - Briquilimab, Fludarabine, Cyclophosphamide, 200 centigray (cGy) Total Body Irradiation

Post-Transplant Cyclophosphamide DRUG

50 mg/kg intravenous (IV) daily on days +3 and +4

Also known as: Post-Transplant Cytoxan, Post-Transplant Neosar

Arm A -Briquilimab, Fludarabine, 200 centigray (cGy) Total Body Irradiation; Arm B - Briquilimab, Fludarabine, Cyclophosphamide, 200 centigray (cGy) Total Body Irradiation

Total Body Irradiation RADIATION

200 centigray (cGy) on day -1

Also known as: TBI

Arm A -Briquilimab, Fludarabine, 200 centigray (cGy) Total Body Irradiation; Arm B - Briquilimab, Fludarabine, Cyclophosphamide, 200 centigray (cGy) Total Body Irradiation

Hematopoietic Cell Transplant PROCEDURE

Stem cell transplant on day 0

Also known as: HCT

Arm A -Briquilimab, Fludarabine, 200 centigray (cGy) Total Body Irradiation; Arm B - Briquilimab, Fludarabine, Cyclophosphamide, 200 centigray (cGy) Total Body Irradiation

Briquilimab DRUG

Single 0.6 mg/kg intravenous (IV) infusion administered between days -13 and day -10

Also known as: JSP191

Arm A -Briquilimab, Fludarabine, 200 centigray (cGy) Total Body Irradiation; Arm B - Briquilimab, Fludarabine, Cyclophosphamide, 200 centigray (cGy) Total Body Irradiation

Cyclophosphamide DRUG

14.5 mg/kg intravenous (IV) daily on days -6 and -5; for 7/8 Unrelated or Haploidentical Donor, prior to transplant.

Also known as: Cytoxan, Neosar

Arm B - Briquilimab, Fludarabine, Cyclophosphamide, 200 centigray (cGy) Total Body Irradiation

Fludarabine DRUG

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.

Also known as: Fludara

Arm A -Briquilimab, Fludarabine, 200 centigray (cGy) Total Body Irradiation; Arm B - Briquilimab, Fludarabine, Cyclophosphamide, 200 centigray (cGy) Total Body Irradiation

Bone Marrow Biopsy PROCEDURE

Screening ≤90 days.

Also known as: BM Bx

Arm A -Briquilimab, Fludarabine, 200 centigray (cGy) Total Body Irradiation; Arm B - Briquilimab, Fludarabine, Cyclophosphamide, 200 centigray (cGy) Total Body Irradiation

Bone Marrow Aspirate PROCEDURE

Screening ≤90 days.

Also known as: BM aspirate

Arm A -Briquilimab, Fludarabine, 200 centigray (cGy) Total Body Irradiation; Arm B - Briquilimab, Fludarabine, Cyclophosphamide, 200 centigray (cGy) Total Body Irradiation

2D echo DIAGNOSTIC_TEST

Screening ≤90 days.

Also known as: Two-dimensional echocardiogram

Arm A -Briquilimab, Fludarabine, 200 centigray (cGy) Total Body Irradiation; Arm B - Briquilimab, Fludarabine, Cyclophosphamide, 200 centigray (cGy) Total Body Irradiation

EKG DIAGNOSTIC_TEST

Screening ≤90 days.

Also known as: Electrocardiogram

Arm A -Briquilimab, Fludarabine, 200 centigray (cGy) Total Body Irradiation; Arm B - Briquilimab, Fludarabine, Cyclophosphamide, 200 centigray (cGy) Total Body Irradiation

PFT's PROCEDURE

Screening ≤90 days.

Also known as: Pulmonary function tests

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 pelvis DIAGNOSTIC_TEST

Baseline ≤28 days.

Also known as: Computed tomography of chest, abdomen and pelvis

Arm A -Briquilimab, Fludarabine, 200 centigray (cGy) Total Body Irradiation; Arm B - Briquilimab, Fludarabine, Cyclophosphamide, 200 centigray (cGy) Total Body Irradiation

Eligibility Criteria

• Age: 6 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• "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.

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institutes of Health Clinical Center (CC): lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Immunologic Deficiency Syndromes

Interventions

Mycophenolic Acid; Tacrolimus; Whole-Body Irradiation; Cyclophosphamide; fludarabine; fludarabine phosphate; Electrocardiography; Respiratory Physiological Phenomena

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Macrolides; Lactones; Radiotherapy; Therapeutics; Investigative Techniques; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Electrodiagnosis; Circulatory and Respiratory Physiological Phenomena

Results Point of Contact

• Title: Dr. Danielle E. Pregent-Arnold
• Organization: National Cancer Institute

danielle.arnold@nih.gov

240-281-3922

Study Officials

• Danielle E Pregent-Arnold, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 15, 2023
• First Posted: June 18, 2023
• Study Start: November 29, 2023
• Primary Completion: October 16, 2025
• Study Completion (Estimated): July 31, 2028
• Last Updated: June 25, 2026
• Results First Posted: May 29, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI).

Locations

US (1)