Allogeneic Hematopoietic Stem Cell Transplant for GATA2 Mutations

Summary

Background:

\- GATA2 deficiency is a disease caused by mutations in the GATA2 gene. It can cause different types of leukemia and other diseases. Researchers want to see if a stem cell transplant can be used to treat this condition. A stem cell transplant will give stem cells from a matching donor (related or unrelated) to a recipient. It will allow the donor stem cells to produce healthy bone marrow and blood cells that will attack the recipient s cancer cells.

Objectives:

\- To see if stem cell transplants are successful at treating GATA2 mutations and related conditions.

Eligibility:

\- Recipients who are between 6 and 70 years of age and have GATA2 deficiency.

Design:

* All participants will be screened with a physical exam and medical history. Blood samples will be collected. Recipients will have imaging studies and other tests.
* Recipients will have chemotherapy or radiation to prepare for the transplant. On the day of the transplant, they will receive the donated stem cells.
* Recipients will stay in the hospital until their condition is stable after transplant.
* Frequent blood tests and scans will be required for the first 6 months after the transplant, followed by less frequent visits over time....

Conditions

• GATA2
• Immunodeficiency
• MDS

Interventions

PROCEDURE

Allogeneic HSCT

Stem cell transplant

DRUG

Busulfan Test dose

0.8 mg/kg IV infusion over 3 hours one time dose administered 5 to 14 days prior to start of preparative regimen (Days -11 to -20)

DRUG

Fludarabine (Fludara, Berlex Laboratories)

40 mg/m2 IV (in the vein) over 30 minutes (in the vein) once daily on Days -6, -5, -4, and -3 or 30 mg/m2 IV over 30 minutes (in the vein) once daily on Days -6, -5, -4, -3, and -2

DRUG

Busulfan (Busulfex)

3.2 mg/kg IV (in the vein) over 3 hours once daily on Days -6, -5, -4 and -3 (weight based dosing). If in Arm B and if poor or very poor risk clonal chromosomal abnormalities, busulfan will also be given on day -2.

DRUG

Cyclophosphamide (CTX, Cytoxan)

14.5 mg/kg IV (in the vein) infusion over 30 minutes once daily on days -6 and -5 (weight based dosing) or 50 mg/kg IV infusion over 2 hours on day -6 (weight based dosing). For post-transplant, 50/kg IV once daily x2 doses on days +3 and +4

PROCEDURE

Total Body Irradiation (TBI)

200 cGy on Day -1

DRUG

Mycophenolate mofetil (MMF)

15mg/kg IV over 2 hours BID starting on day +5 will continue until day +35 (+/- 2 days)

DRUG

Tacrolimus

0.02mg/kg IV continuous infusion over 24 hours starting on day +5 until day +180

BIOLOGICAL

Equine Anti-Thymocyte Globulin

(Deleted this intervention per amendment I): 30mg/kg IV (in the vein)once daily x 3 days on Days -6, -5, -4 (3 doses total)

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

2013-07-24

Primary Completion

2027-12-31

Completion

2028-12-31

FDA Drug

Yes

Countries

• United States

Study Locations