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RecruitingNCT01861106Updated Oct 16, 2026

Allogeneic Hematopoietic Stem Cell Transplant for GATA2 Mutations

A Phase 2 interventional study of Allogeneic HSCT and Busulfan Test dose in GATA2, Immunodeficiency and MDS, sponsored by National Cancer Institute (NCI). Recruiting at 1 site in United States. Open to participants aged 6 Years to 70 Years. Per ClinicalTrials.gov, last updated 2026-10-16.

Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Treatment

From the registry’s dates

  • Started Jul 2013; still recruiting 13 years 3 months later.
Phase
Phase 2
Study type
Interventional
Enrollment
144
Allocation
Non-randomized
Ages
6 Years to 70 Years
Sex
All
01

Study 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....
Read the detailed description

Background:

Genetic and sporadic mutations on one allele of the GATA2 gene lead to a syndrome termed MonoMAC. MonoMAC is characterized by: 1) infections with Mycobacterium avium complex (MAC) 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), and 4) mutations on one allele of GATA2 in most participants. We propose to evaluate the efficacy and safety of allogeneic hematopoietic stem cell transplantation (HSCT) using different conditioning regimens from different donor sources in reconstituting normal hematopoiesis and reversing the disease phenotype in participants with mutations in GATA2, or the clinical syndrome of MonoMAC.

Objectives: Primary:

-To determine whether allogeneic hematopoietic stem cell transplant (HSCT) approach reconstitutes normal hematopoiesis and reverses the disease phenotype by one year posttransplant in participants with mutations in GATA2 or the clinical syndrome of MonoMAC.

Eligibility:

  • Recipients ages 6-70 years old with mutations in GATA2 or the clinical syndrome of MonoMAC. Clinical history of at least one serious or disfiguring infection and GATA2 bone marrow immunodeficiency disorder with loss of one or more immune populations in the bone marrow including monocytes, Natural Killer (NK) cells, and B-lymphocytes, with or without additional cytopenias involving the red blood cell, neutrophil, or platelet compartment.
  • Have a 10/10 or a 9/10 or an 8/10 HLA-matched related or unrelated donor (HLA -A, -B, -C, DRB1, DQB1 by high resolution typing) or a haploidentical related donor; unrelated donors are identified through the National Marrow Donor Program.

Design: Two Arms

  • Participants with mutations in GATA2, or the clinical syndrome of MonoMAC, with a 10/10 (or 9/10 matched if the mismatch is at DQ) HLA-matched related or unrelated donor will receive a pre-transplant conditioning regimen consisting of fludarabine 40 mg/m2 IV once daily for 4 days on days -6, -5, -4, and -3, busulfan based on pharmacokinetic levels from test dose or real time pharmacokinetics (PKs) (3.2 mg/kg IV will be the default dose) once daily on days -6, -5, -4, and -3, and HSCT on day 0.
  • Participants with mutations in GATA2, or the clinical syndrome of MonoMAC, with a 9/10 or an 8/10 HLA-matched related or unrelated donor (if the mismatch is not at DQ) or with a haploidentical related donor, will receive a pre-transplant conditioning regimen consisting of cyclophosphamide 14.5 mg/kg IV once daily for 2 days on days -6 and -5, busulfan based on pharmacokinetic levels from test dose or real time PKs ( 3.2 mg/kg IV will be the default dose) once daily on days -4, -3, (if poor or very poor risk clonal cytogenetic abnormalities are present, then three days of busulfan IV once daily on days -4, -3, and -2 will be given), fludarabine 30 mg/m2 IV once daily for 5 days on days -6 to -2, 200 cGy TBI on day -1, and HSCT on day 0.
  • Post-transplant immunosuppression for GVHD prophylaxis for recipients of all groups will consist of cyclophosphamide 50 mg/kg IV once daily 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 graft-versus- host disease, tacrolimus will be stopped or tapered at approximately day +180.
02

Conditions studied

  • GATA2
  • Immunodeficiency
  • MDS

Keywords

  • Allogeneic Donors
  • Peripheral Blood Stem Cell
  • Immunodeficiency
  • Myelodysplasia
  • Haploidentical
03

In context

Immunologic Deficiency Syndromes

204 studies on the registry are indexed under Immunologic Deficiency Syndromes; 50 are open to participants now.

This study's planned enrollment of 144 is above the median of 30 across 123 interventional studies indexed under Immunologic Deficiency Syndromes.

Browse Immunologic Deficiency Syndromes studies →

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,556 studies on the registry; 336 are open to participants now.

Of its 411 completed or terminated interventional studies of FDA-regulated products, 373 (91%) have results posted.

Browse National Cancer Institute (NCI) studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
6 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

  • ELIGIBILITY CRITERIA:

Inclusion criteria

INCLUSION CRITERIA- Recipient

  1. Patient age of 6-70 years.
  2. Mutation in the GATA2 gene, or evidence of loss of expression of one allele of GATA2, by cDNA analysis performed by a CLIA certified laboratory, or the clinical syndrome of MonoMAC.
  3. Clinical history of at least one serious or disfiguring infection and/or GATA2 bone marrow immunodeficiency disorder with lose of one or more immune populations in the bone marrow including monocytes, Natural Killer (NK) cells, and B-lymphocytes, with or without additional cytopenias involving the red blood cell, neutrophil, or compartment.
  4. Availability of a 10/10 or 9/10 or 8/10 HLA-matched related or unrelated donor, or a haploidentical related donor.
  5. Patients may have evidence of MDS with one or more peripheral blood cytopenias and greater than 5% blasts but must have less than 10% blasts in the bone marrow in the absence of filgrastim in order to proceed directly to transplant. The majority of patients with MDS will have less than 5% blasts.
  6. Disease status: Patients are to be referred in remission for evaluation. Should a patient have progressive disease with >10% blasts on screening/baseline bone marrow , the patient may receive standard treatment under the current study prior to proceeding with transplant. Once the patient has \<10% blasts, they may proceed to transplant. The patient may also be referred back to their primary hematologist or oncologist for treatment. If this course of action is not in the best interest of the patient according to the clinical judgment of the PI/LAI, then the patient may receive standard treatment for the malignant disease or hematological disorder under the current study. If under either of these settings, it becomes apparent that the participant will not be able to proceed to transplant, then he/she must come off study. Recipient-Subjects receiving a standard therapy will be told about the therapy, associated risks, benefits and alternatives of the proposed therapy, and availability of receiving the same treatment elsewhere, outside of a research protocol.
  7. > 40%, preferably by 2-D echocardiogram obtained within 90 days prior to initiation of conditioning therapy.
  8. Creatinine: Adult patients: \<= 2.0 mg/dl and >= 30 ml/min; Pediatric patients (\<18 years old): creatinine \<1.5 mg/dL and a creatinine clearance, using the Schwartz Formula, > 30 mL/min/1.73m\^2.
  9. Serum conjugated \< 2.5 mg/dl; serum and AST \<= 5 times .
  10. Pulmonary function tests: and DLCO >30% Note: For children who are unable to cooperate for PFTs, the criterion is: No evidence of dyspnea at rest, no exercise intolerance, and no requirement for supplemental oxygen therapy
  11. Ability of patient or Legally Authorized Representative (LAR) (if the patient is deemed by the treating physician to be cognitively impaired or questionably impaired in such a way that the ability of the patient to give is questionable) to understand and the willingness to sign a written informed consent document indicating that they are aware of the nature of this study or written informed consent obtained from parent or legal guardian if subject is a minor.
  12. As therapeutic agents used in this trial may be harmful to a fetus, women of and men must agree to use adequate (hormonal or barrier method of birth control; abstinence) prior to study entry and for at least one-year post-allo . Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in the study, she should inform her treating physician immediately.
  13. All transplant patients remain in the NIH hospital or, if discharged, stay close to the NIH for a minimum of 100 days after transplant or longer, if there are complications. An adult caregiver must be with the patient at all times from discharge to day 100.

Exclusion criteria

EXCLUSION CRITERIA- Recipient

  1. Patients who are receiving any other agents with the exception of virus- specific cytotoxic T-cells for the treatment of viral infection/reactivation prior to allo
  2. -positive patients are ineligible because these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
  3. History of allergic reactions attributed to compounds of similar chemical or biological composition to agents (, cyclophosphamide, busulfan) used in the study
  4. Chronic active . Patient may be hepatitis B core antibody positive. For patients with a concomitant positive hepatitis B surface antigen, patients will require a hepatology consultation. The risk-benefit profile of transplant and hepatitis B will be discussed with the patient, and eligibility determined by the PI or Lead Associate Investigator.
  5. History of psychiatric disorder which may compromise compliance with transplant protocol, or which does not allow for appropriate .
  6. Active infection to antimicrobial therapy. Exceptions may be made per PI discretion for patients with disseminated mycobacterial infections if the potential benefit of HSCT is thought to outweigh the risks.
  7. Active CNS involvement by (patients with known positive CSF cytology or parenchymal lesions visible by prior CT or MRI).
  8. Pregnant or lactating.
  9. The effects on breast-milk are unknown and may be harmful to the infant; therefore, women should not breast feed during the interval from study entry to one year post-transplant.
  10. Presence of active malignancy in another organ system other than the hematopoietic, except when driven by viruses in which case the immune reconstitution after transplant may control the malignancy. This includes solid tumors not in remission.
Terms in these criteria, in plain language(18)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Platelets

Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.

Biopsy and archival tissue

A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.

Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.

LVEF (left ventricular ejection fraction)

The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.

Creatinine clearance (CrCl)

How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.

Bilirubin

A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.

Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

FEV1

From a breathing test (spirometry): how much air you can blow out in the first second. Often given as a percentage of what is expected for your age, height and sex.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

Allogeneic and autologous transplant

Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

Corticosteroids (steroids)

Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.

Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.

Hepatitis B tests

Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.

Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.

Relapsed and refractory

Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
144 participants (estimated)

Study arms

  • Active comparator
    Arm A

    10/10 HLA Matched Related Donor or Unrelated Donor or 9/10 HLA with DQ mismatch Transplant

    Procedure: Allogeneic HSCT · Drug: Busulfan Test dose · Drug: Fludarabine (Fludara, Berlex Laboratories) · Drug: Busulfan (Busulfex) · Drug: Mycophenolate mofetil (MMF) · Drug: Tacrolimus

  • Active comparator
    Arm B

    9/10 or 8/10 HLA Match Related Donor or Unrelated Donor or Haploidentical Donor Transplant

    Procedure: Allogeneic HSCT · Drug: Busulfan Test dose · Drug: Fludarabine (Fludara, Berlex Laboratories) · Drug: Busulfan (Busulfex) · Drug: Cyclophosphamide (CTX, Cytoxan) · Drug: Mycophenolate mofetil (MMF) · Drug: Tacrolimus

  • Active comparator
    Arm C (combined with Arm B per Amendment N)

    Haploidentical Related Donor Transplant

    Procedure: Allogeneic HSCT · Drug: Busulfan Test dose · Drug: Fludarabine (Fludara, Berlex Laboratories) · Drug: Busulfan (Busulfex) · Drug: Cyclophosphamide (CTX, Cytoxan) · Procedure: Total Body Irradiation (TBI) · Drug: Tacrolimus

  • Active comparator
    Arm D (Deleted this arm per amendment I)

    Umbilical Cord Blood Transplant

    Procedure: Allogeneic HSCT · Drug: Fludarabine (Fludara, Berlex Laboratories) · Drug: Cyclophosphamide (CTX, Cytoxan) · Procedure: Total Body Irradiation (TBI) · Biological: Equine Anti-Thymocyte Globulin

  • No intervention
    Arm E (Deleted this arm per amendment O)

    Donor

Interventions

  • ProcedureAllogeneic HSCT

    Stem cell transplant

  • DrugBusulfan 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)

  • DrugFludarabine (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

  • DrugBusulfan (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.

  • DrugCyclophosphamide (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

  • ProcedureTotal Body Irradiation (TBI)

    200 cGy on Day -1

  • DrugMycophenolate mofetil (MMF)

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

  • DrugTacrolimus

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

  • BiologicalEquine 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)

06

What researchers measure

Primary outcomes

  1. To determine whether allogeneic HSCT approach results in engraftment and restores normal hematopoiesis by one year in patients with mutations GATA2.

    Determination that engraftment has occurred, normal hematopoiesis has been restored and the clinical phenotype after allogeneic HSCT has been reversed

    Time frame: 1 year after completing ASCT

Secondary outcomes

  1. To determine the safety of allogeneic HSCT for patients with mutations in GATA2

    Fractions of patients with transplant related toxicity will be reported along with 95% confidence intervals

    Time frame: 3 years

  2. To determine the incidence of grade III-IV acute GVHD

    fractions will be reported using simple estimates along with 95% two-sided confidence intervals

    Time frame: 100 days

  3. To determine the incidence of chronic graft-versus-host disease

    Fractions of patients with transplant related toxicity as well as the fractions with aGVHD and cGVHD will be reported along with 95% confidence intervals.

    Time frame: 1 year and 2 years post-transplant

  4. To characterize the immune reconstitution inflammatory syndrome (IRIS)

    fraction of patients who experience a reversal of the described immunologic abnormalities will be reported along with a 95% two-sided confidence interval. Fractions will be compared using Fisher's exact test.

    Time frame: Days 30, 100, 6 months, and one year post-transplant

  5. To characterize the immune reconstitution in 10/10 matched related and unrelated donor transplant recipients and haploidentical related donor transplants who receive GVHD prophylaxis

    Fractions will be compared using Fisher's exact test.

    Time frame: Days 30, 100, 6 months, and one year post-transplant

  6. Overall survival, and disease-free survival.

    determined using the Kaplan-Meier method for all evaluable patients beginning at their date of transplant, along with the median value and the 95% confidence interval at the median

    Time frame: 3 years post-transplant

07

Study locations

1 of 1 sites recruiting
  • National Institutes of Health Clinical Center
    Bethesda, Maryland 20892, United States
    Recruiting
08

References and documents

Publications

  • West RR, Bauer TR, Tuschong LM, Embree LJ, Calvo KR, Tillo D, Davis J, Holland SM, Hickstein DD. A novel GATA2 distal enhancer mutation results in MonoMAC syndrome in 2 second cousins. Blood Adv. 2023 Oct 24;7(20):6351-6363. doi: 10.1182/bloodadvances.2023010458. PubMed 37595058 ↗
  • Wu Z, Gao S, Diamond C, Kajigaya S, Chen J, Shi R, Palmer C, Hsu AP, Calvo KR, Hickstein DD, Holland SM, Young NS. Sequencing of RNA in single cells reveals a distinct transcriptome signature of hematopoiesis in GATA2 deficiency. Blood Adv. 2020 Jun 23;4(12):2656-2670. doi: 10.1182/bloodadvances.2019001352. PubMed 32556286 ↗

Individual participant data

Plan to share: Yes — All IPD recorded in the medical record will be shared with intramural investigators upon request.

Supporting information: Study protocol, Statistical analysis plan, Informed consent form

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.

09

Updates

3 registry updates since Sep 25, 2026
Minor edits
Nothing that changes what the study is or who can join. Edited: description and verification date
3 updates, last Oct 16, 2026
Show all 3 updates
  1. Oct 16, 2026
    Minor edits only
    + 2 other changes: verification date and description
  2. Oct 5, 2026
    Minor edits only
    + 1 other change: verification date
  3. Sep 28, 2026
    Minor edits only
    + 1 other change: description

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

10

Registry details

Key details

Study ID
NCT01861106
Lead sponsor
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
May 23, 2013
Start date
Jul 24, 2013
Primary completion
Dec 31, 2027 (estimated)
Completion
Dec 31, 2028 (estimated)
Last update
Oct 16, 2026

Study contacts

Danielle E Pregent-Arnold, M.D.
Contact
danielle.arnold@nih.gov
(240) 281-3922
Danielle E Pregent-Arnold, M.D.
principal investigator · National Cancer Institute (NCI)

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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Studies of the drugs tested here: Fludarabine · Busulfan · Cyclophosphamide · Mycophenolic Acid · Tacrolimus · Antilymphocyte Serum

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