Multicenter, open-label, uncontrolled study of azacitidine therapy for juvenile myelomonocytic leukemia

JRCT ID: jRCTs041210044

Registered date:26/07/2021

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Juvenile myelomonocytic leukemia; JMML
• Date of first enrollment: 29/07/2021
• Target sample size: 30
• Study type: Interventional

Intervention(s)

After diagnosis of JMML and enrollment in the JMML-20 study, azacitidine therapy is started.
Azacitidine is administered as a 10-minute IV infusion of 75 mg/m2 once a day for 7 days (days 1-7), followed by a 21-day rest. This is one cycle of 7 days every 4 weeks. A minimum of 3 cycles should be continued unless there is evidence of disease progression. Study treatment should be limited to 6 cycles if possible, but donor coordination and other factors may allow up to 12 cycles if necessary.
If the patient is less than 6 months of age, the dose should be changed to 2/3 of the body surface area equivalent.
If the child is between 6 months and 12 months (1 year old), the dosage should be changed to 3/4 of the body surface area.

Outcome(s)

• Primary Outcome: Clinical response rate (cCR + cPR) after 3 cycles of azacitidine therapy

Secondary Outcome

Adverse Events (AEs)

1-year, 3-year and 5-year overall survival rates
Causes of death
1-year, 3-year and 5-year transplant-free survival rates
1-year, 3-year and 5-year relapse-free survival rates
Clinical response at each cycle
Genetic response for each cycle
Assessment of quality of life of the affected child obtained from a questionnaire by the individual and family (proxy assessment) 5 years after enrollment. Quality of life assessment of the affected child obtained from the physician.

Percentage of hematopoietic cell transplants performed.
Conditioning regimen for hematopoietic cell transplantation
Time to first hematopoietic cell transplantation
Engraftment rate after initial hematopoietic cell transplantation
Leukemia-free survival after hematopoietic cell transplantation (time from initial hematopoietic cell transplantation to progression of primary disease or death)
Overall survival after hematopoietic cell transplantation (time from initial hematopoietic cell transplantation to death)
Time to recurrence after hematopoietic cell transplantation (time from initial hematopoietic cell transplantation to recurrence)
Time to transplantation-related death after hematopoietic cell transplantation (time from initial hematopoietic cell transplantation to transplantation-related death)
Cumulative incidence of post-transplant acute GVHD (grades II - IV)
Cumulative incidence of post-transplant acute GVHD (grades III-IV)
Cumulative Incidence of chronic GVHD after transplantation
Cumulative recurrence rate at 3 years after transplantation
Cumulative transplant-related complication mortality at 3 years after transplant
3-year GVHD-free recurrence-free survival after transplantation

Key inclusion & exclusion criteria

• Age minimum: Not applicable
• Age maximum: < 10age old
• Gender: Both

Include criteria

(1) Cases with a clinical diagnosis of JMML based on the JMML diagnostic criteria.
(2) Have submitted or are able to submit samples for central testing.
(3) Consent for CHM-14 was obtained prior to obtaining consent to participate in this study.
(4) Age at diagnosis is less than 10 years old.
(5) The patient has sufficient organ function to meet the following three criteria at the same time. Laboratory values within 7 days before the date of enrollment.
a) D-Bil level: less than 1.5 mg/dL
b) Creatinine: less than 3 times the upper limit of the age-specific test reference value
c) Left ventricular ejection fraction (EF) >=50% by echocardiography
(6) Adequate explanations and written consent have been obtained from the proxy.

Exclude criteria

(1) Noonan syndrome (a case of PTPN11 germ cell mutation)
(2) Associated with difficult-to-control infections (including active tuberculosis and HIV antibody-positive cases).
(3) Relapse cases with a history of hematopoietic cell transplantation.
(4) Any other case deemed inappropriate by the doctor in charge.

Related Information

• Primary Sponsor: Muramatsu Hideki
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development