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

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

Interventions

DRUG

Mycophenolate Mofetil

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

DRUG

Tacrolimus

0.02 mg/kg IV daily starting on day +5

DRUG

Post-Transplant Cyclophosphamide

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

RADIATION

Total Body Irradiation

200cGy on day -1

PROCEDURE

Hematopoietic Cell Transplant

stem cell transplant on day 0

DRUG

Briquilimab

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

DRUG

Cyclophosphamide

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

DRUG

Fludarabine

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.

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Danielle E Pregent-Arnold, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

6 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-11-29

Primary Completion

2025-10-16

Completion

2028-07-31

FDA Drug

Yes

Countries

• United States

Study Locations