Efficacy of mercaptopurine in leukemia patients with relapse after allogeneic stem cell transplantation

JRCT ID: jRCT1051200006

Registered date:27/04/2020

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Acute Leukemia, Myelodysplastic syndromes overt leukemia
• Date of first enrollment: 27/04/2020
• Target sample size: 5
• Study type: Interventional
• Intervention(s): Administration of mercaptopurine

Outcome(s)

• Primary Outcome: Anti-leukemia effect of mercaptopurine in each case

Secondary Outcome

1. Blast count and evaluation of leukemia specific DNA or chimeric mRNA by PCR, FISH and G-banding method in patients bone marrow.
2. Blood count and blast count in peripheral blood.
3. Adverse effect and safety of mercaptopurine administration.

Key inclusion & exclusion criteria

• Age minimum: Not applicable
• Age maximum: Not applicable
• Gender: Both

Include criteria

1) Acute leukemia or myelodysplastic syndromes (MDS) overt leukemia with relapse after allogeneic stem-cell transplantation
2) NUDT15 R139C heterozygous or homozygous patients
3) Donor lymphocytes harboring wild-type NUDT15
4) Performance status (PS) should be 2 or less in the ECOG criteria.
5) GVHD should be controlled well to acute GVHD grade I or lower and prednisolone dosage less than 0.5 mg/kg.
6) No severe liver dysfunction; serum AST and ALT should be 3 times the upper normal limit or lower, serum ALP should be 2.5 times the upper normal limit or lower, and total bilirubin should be 2.0 mg/dL or lower.
7) No severe renal dysfunction; serum creatinine should be 2.0 mg/dL or lower.
8) No severe cardiac dysfunction; ejection fraction (EF) should be 50% or more in ultrasonic echocardiography.
9) No severe pulmonary dysfunction; forced expiratory volume in 1 second (FEV1) should be 70% or more.
10) No severe gastroenterology symptoms; the number of stools per day should be three times or less, or the volume of stools per day should be less than 500 mL.
11) No severe infection; no significant findings indicating any infections in computed tomography of chest and abdomen, no significant symptoms caused by viral infection that can be caused after allogeneic stem cell transplantation, including macrohematuria (hemorrhagic cystitis), bloody stool (gastroenteritis), and loss of memorization and consciousness (encephalitis).
12) Written informed consent to participate in the research by himself / herself. In the case of patients with younger than 20 years old, the written consent of authorized representative of the participant is also obtained. The authorized representative should be the parents basically but also may be the grandparents or relatives living together who are considered to be able to speak for the will and interests of the participant.

Exclude criteria

Exclude if any of the following applies.
1) Performance status (PS) is 3 or more in the ECOG criteria.
2) GVHD is not controlled well; acute GVHD grade II or more, or requirement of prednisolone more than 0.5 mg/kg.
3) Central nervous system (CNS) involvement of leukemia cells.
4) Severe liver dysfunction; serum AST and ALT is 3 times more than the upper normal limit, serum ALP is 2.5 times more than the upper normal limit, or total bilirubin is more than 2.0 mg/dL or lower.
5) Severe renal dysfunction; serum creatinine is more than 2.0 mg/dL.
6) Severe cardiac dysfunction; ejection fraction (EF) is less than 50% in ultrasonic echocardiography.
7) Severe pulmonary dysfunction; forced expiratory volume in 1 second (FEV1) is less than 70%.
8) Severe gastroenterology symptoms; the number of stools per day is four times or more, or the volume of stools per day is 500 mL or more.
9) Active infection;
-computed tomography (CT) of chest and abdomen shows active infections requiring hospitalization.
-symptoms caused by viral hemorrhagic cystitis including macrohematuria.
-symptoms caused by viral gastroenteritis including bloody stool and/or pathological observation of intranuclear inclusion bodies in biopsy samples from digestive tract such as stomach, duodenum, and/or colon.
-symptoms caused by viral encephalitis including loss of memorization and consciousness, and/or findings of signs indicating viral encephalitis in CT and MRI.
-active infection with herpes zoster virus.
10) Patients who cannot stop taking contraindicated drugs including febuxostat, topiroxostat, and allopurinol.
11) Patients with hypersensitivity when using thiopurine in the past
12) Others, when the doctor judges inappropriate.

Related Information

• Primary Sponsor: Kawahara Masahiro