Allogeneic Hematopoietic Stem Cell Transplant for Patients With Mutations in GATA2 or the MonoMAC Syndrome

Who is this study for? Patients with mutations in GATA2 or the monoMAC syndrome
Status: Recruiting
Location: See location...
Intervention Type: Drug, Biological, Procedure
Study Type: Interventional
Study Phase: Phase 2
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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 6
Maximum Age: 70
Healthy Volunteers: f
View:

• 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.

Locations
United States
Maryland
National Institutes of Health Clinical Center
RECRUITING
Bethesda
Contact Information
Primary
Danielle E Pregent-Arnold, M.D.
danielle.arnold@nih.gov
(240) 281-3922
Time Frame
Start Date: 2013-07-24
Estimated Completion Date: 2028-12-31
Participants
Target number of participants: 144
Treatments
Active_comparator: Arm A
10/10 HLA Matched Related Donor or Unrelated Donor or 9/10 HLA with DQ mismatch Transplant
Active_comparator: Arm B
9/10 or 8/10 HLA Match Related Donor or Unrelated Donor or Haploidentical Donor Transplant
Active_comparator: Arm C (combined with Arm B per Amendment N)
Haploidentical Related Donor Transplant
Active_comparator: Arm D (Deleted this arm per amendment I)
Umbilical Cord Blood Transplant
No_intervention: Arm E (Deleted this arm per amendment O)
Donor
Sponsors
Leads: National Cancer Institute (NCI)

This content was sourced from clinicaltrials.gov

Similar Clinical Trials