Allogeneic Hematopoietic Stem Cell Transplant for GATA2 Mutations
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age6-70
SponsorNational Cancer Institute (NCI)
About this trial
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 criteria
This trial does not accept healthy volunteersQualifiers
Recipient
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.
Disqualifiers
Recipient
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
Trial design
Design model
Parallel
Treatments tested in this trial
Allogeneic HSCT
Procedure/SurgeryStem cell transplant
Busulfan Test dose
Drug0.8 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)
Fludarabine (Fludara, Berlex Laboratories)
Drug40 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
Busulfan (Busulfex)
Drug3.2 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.
Cyclophosphamide (CTX, Cytoxan)
Drug14.5 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
Total Body Irradiation (TBI)
Procedure/Surgery200 cGy on Day -1
Mycophenolate mofetil (MMF)
Drug15mg/kg IV over 2 hours BID starting on day +5 will continue until day +35 (+/- 2 days)
Tacrolimus
Drug0.02mg/kg IV continuous infusion over 24 hours starting on day +5 until day +180
Equine Anti-Thymocyte Globulin
Biological/Vaccine(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)
Treatment groups
144 Participants
are divided into 5 treatment groupsGroup A: Arm AActive comparator 6 interventions
Group B: Arm BActive comparator 7 interventions
Group C: Arm C (combined with Arm B per Amendment N)Active comparator 7 interventions
Group D: Arm D (Deleted this arm per amendment I)Active comparator 5 interventions
Group E: Arm E (Deleted this arm per amendment O)No intervention 0 interventions
Trial outcomes
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 ASCTSecondary 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 years2
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 days3
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-transplant4
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-transplantSponsors and contacts
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Source ClinicalTrials.gov