Allogeneic Hematopoietic Stem Cell Transplant for GATA2 Mutations
2 other identifiers
interventional
144
1 country
1
Brief 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....
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jul 2013
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 21, 2013
CompletedFirst Posted
Study publicly available on registry
May 23, 2013
CompletedStudy Start
First participant enrolled
July 24, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2028
May 1, 2026
April 3, 2026
14.4 years
May 21, 2013
April 30, 2026
Conditions
Keywords
Outcome Measures
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
1 year after completing ASCT
Secondary Outcomes (6)
To determine the safety of allogeneic HSCT for patients with mutations in GATA2
3 years
To determine the incidence of grade III-IV acute GVHD
100 days
To determine the incidence of chronic graft-versus-host disease
1 year and 2 years post-transplant
To characterize the immune reconstitution inflammatory syndrome (IRIS)
Days 30, 100, 6 months, and one year post-transplant
To characterize the immune reconstitution in 10/10 matched related and unrelated donor transplant recipients and haploidentical related donor transplants who receive GVHD prophylaxis
Days 30, 100, 6 months, and one year post-transplant
- +1 more secondary outcomes
Study Arms (5)
Arm A
ACTIVE COMPARATOR10/10 HLA Matched Related Donor or Unrelated Donor or 9/10 HLA with DQ mismatch Transplant
Arm B
ACTIVE COMPARATOR9/10 or 8/10 HLA Match Related Donor or Unrelated Donor or Haploidentical Donor Transplant
Arm C (combined with Arm B per Amendment N)
ACTIVE COMPARATORHaploidentical Related Donor Transplant
Arm D (Deleted this arm per amendment I)
ACTIVE COMPARATORUmbilical Cord Blood Transplant
Arm E (Deleted this arm per amendment O)
NO INTERVENTIONDonor
Interventions
Stem cell transplant
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)
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.
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
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
200 cGy on Day -1
15mg/kg IV over 2 hours BID starting on day +5 will continue until day +35 (+/- 2 days)
0.02mg/kg IV continuous infusion over 24 hours starting on day +5 until day +180
(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)
Eligibility Criteria
You may qualify if:
- Patient age of 6-70 years.
- 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.
- 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 platelet compartment.
- Availability of a 10/10 or 9/10 or 8/10 HLA-matched related or unrelated donor, or a haploidentical related donor.
- 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.
- 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 biopsy, 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.
- Left ventricular ejection fraction \> 40%, preferably by 2-D echocardiogram obtained within 90 days prior to initiation of conditioning therapy.
- Creatinine: Adult patients: \<= 2.0 mg/dl and creatinine clearance \>= 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.
- Serum conjugated bilirubin \< 2.5 mg/dl; serum ALT and AST \<= 5 times upper limit of normal.
- Pulmonary function tests: FEV1 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
- 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 informed consent is questionable) to understand and the willingness to sign a written informed consent document indicating that they are aware of the investigational nature of this study or written informed consent obtained from parent or legal guardian if subject is a minor.
- As therapeutic agents used in this trial may be harmful to a fetus, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for at least one-year post-allo HSCT. 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.
- 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.
You may not qualify if:
- Patients who are receiving any other investigational agents with the exception of virus- specific cytotoxic T-cells for the treatment of viral infection/reactivation prior to allo HSCT
- HIV-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.
- History of allergic reactions attributed to compounds of similar chemical or biological composition to agents (steroids, cyclophosphamide, busulfan) used in the study
- Chronic active hepatitis B. 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.
- History of psychiatric disorder which may compromise compliance with transplant protocol, or which does not allow for appropriate informed consent.
- Active infection refractory to antimicrobial therapy.
- Active CNS involvement by malignancy (patients with known positive CSF cytology or parenchymal lesions visible by prior CT or MRI).
- Pregnant or lactating.
- 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.
- 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.
- No available 10/10 or 9/10 or 8/10 HLA-matched related or unrelated donor, or haploidentical related donor.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Related Publications (2)
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.
PMID: 37595058DERIVEDWu 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.
PMID: 32556286DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Danielle E Pregent-Arnold, M.D.
National Cancer Institute (NCI)
Central Study Contacts
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
May 21, 2013
First Posted
May 23, 2013
Study Start
July 24, 2013
Primary Completion (Estimated)
December 31, 2027
Study Completion (Estimated)
December 31, 2028
Last Updated
May 1, 2026
Record last verified: 2026-04-03
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.
All IPD recorded in the medical record will be shared with intramural investigators upon request.