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

NCT05907746 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: 10001531001531-C
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

Background: People with 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 (1)

• 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

  Fraction of evaluable participants reported along with one-sided 90% confidence intervals and a two-sided 95% confidence interval

  100 days post-transplant

Secondary Outcomes (6)

• 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

  1 year post-transplant

• The safety of allogeneic HCT in participants with GATA2 deficiency conditioned with Briquilimab

  3 years post-transplant

• 3-year overall survival

  3 years post-transplant

• 3-year event-free survival

  3 years post-transplant

• 3-year incidence of secondary graft failure

  3 years post-transplant

Study Arms (2)

Arm A

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

Arm B

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

Interventions

Mycophenolate Mofetil DRUG

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

Arm A; Arm B

Tacrolimus DRUG

0.02 mg/kg IV daily starting on day +5

Arm A; Arm B

Post-Transplant Cyclophosphamide DRUG

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

Arm A; Arm B

Total Body Irradiation RADIATION

200cGy on day -1

Arm A; Arm B

Hematopoietic Cell Transplant PROCEDURE

stem cell transplant on day 0

Arm A; Arm B

Briquilimab DRUG

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

Arm A; Arm B

Cyclophosphamide DRUG

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

Arm B

Fludarabine DRUG

30 mg/m2 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.

Arm A; Arm B

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 GATA2 gene, predicted to be deleterious or previously reported in GATA2 deficiency as determined by targeted GATA2 sequencing performed at the 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 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., AML, CMML). Note: participants with 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-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 Cancer Institute (NCI): lead

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

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

Study Officials

• Danielle E Pregent-Arnold, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

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: 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: November 3, 2025

Record last verified: 2025-10-30

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 BTRIS and with the permission of the study PI.

Locations

US (1)