Efficacy and safety study of a therapeutic regimen using Tamibarotene (Am80) and arsenic trioxide (ATO) in combination with Gemtuzumab Ozogamicin (GO) as a post-remission therapy for relapsed acute promyelocytic leukemia (APL)

JRCT ID: jRCTs041190101

Registered date:19/12/2019

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Relapsed acute promyelocytic leukemia
• Date of first enrollment: 04/02/2020
• Target sample size: 39
• Study type: Interventional

Intervention(s)

Treatment is in order of induction therapy followed by consolidation therapy.
(1) ATO (infusion) and Tamibarotene (in oral use) for therapy of remission induction
Note: If the number of APL cells is large, add an anti-cancer drug (idarubicin) for 2 days.
(2) Intrathecal injection: injection of anticancer agents (methotrexate and cytarabine) into the lumbar spinal cavity.
(3) Consolidation therapy with ATO and Tamibarotene: Two 5-week treatments.
(4) Consolidation therapy with GO (infusion): Usually 2 weeks apart for 2 weeks.

Outcome(s)

• Primary Outcome: 1 year event free survival rate (EFS)

Secondary Outcome

1) Contents and incidence of adverse events in reinduction therapy and consolidation therapy
2) Completion rate of this trial
3) Complete remission (CR) induction rate
4) 1 year, 3 year overall survival rate (Overall Survival; OS)
5) Rate of additional chemotherapy(Idarubicin) during reinduction therapy
6) Risk factor analysis affecting EFS
7) Analysis of one-, three-year EFS, DFS, CIR based on hematological remission and hematological relapse
8) Analysis of one- and three-year mDFS and mCIR based on molecular remission and molecular relapse
9) PML-RARA RA, ATO resistant gene mutation and therapeutic effect, prognostic relationship

Key inclusion & exclusion criteria

• Age minimum: >= 16age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Patients who meet all the following criteria:
(1)APL diagnosed by first relapsed CD33-positive acute promyelocytic leukemia cases (chromosome test [t (15; 17) translocation] or genetic test (PML-RARA gene), secondary acute promyelocytic leukemia also). Hematological recurrence cases and molecular recurrence cases even in hematological remission are registered.
(2) Patients who have not started treatment for recurrence
(3) Patients who are 16 years or older at the time of obtaining consent
(4) Patients with ECOG PS 0-2
(5)Have sufficient heart, lung, liver and kidney function. Based on the following.
Serum bilirubin <2.0 mg / dL
Serum creatinine <2.0 mg / dL
PaO2 60 mmHg or more or SpO2 93% or more before treatment.
The chest x-ray (PA) and cardiothoracic ratio should be 50% or less.
If cardiac enlargement is observed, perform cardiac ultrasonography and have an EF of 50% or more.
Do not notice serious electrocardiographic abnormalities.
Satisfy the arsenic trioxide administration standard QTc <500 msec without severe QTc (QTcB or QTcF) prolongation.
(6) Patients who have obtained written consent from the person voluntarily to participate in the trial after sufficiently explaining this study. For minors, the consent of the person in charge must also be obtained along with the individual.
(7)Patients receiving treatment at JALSG participating facilities that meet arsenic trioxide drug use standards and disposal standards.
(8) Asian patients

Exclude criteria

Patients who fall under any of the following will not be included in this study.
(1) Myelodysplastic syndrome (MDS) -derived or atypical acute leukemia
(2) Extramedullary recurrence cases
(3) Patients planning autologous or allogeneic hematopoietic stem cell transplantation (at the start of treatment)
(4) Patients with Grade 4 infection (including active tuberculosis, atypical mycobacterial disease)
(5) HIV antibody positive, HBs antigen positive, HCV antibody positive (However, if HBs antigen negative and HBc antibody positive or HBs antibody positive, HBV-DNA quantitative test is measured, if it exceeds detection sensitivity Dosing, not excluding, nucleic acid analogues)
(6) Patients with a history of myocardial infarction or heart failure
(7) Diabetic patients with poor control
1) Fasting blood glucose less than 250 mg / dL (equivalent to grade 1) can not be maintained even by insulin administration.
2) Insulin administration causes hypoglycemic attack more than twice a day.
(8) Patients with liver cirrhosis
(9) Patients who have been treated with tamibarotene or arsenic trioxide before and who have serious adverse events, patients with hypersensitivity
(10) If you have any of the following mental disorders.
1) There is a high degree of mood swings that interferes with daily life due to psychiatric specialty treatment or medication.
2) Requires monitoring or restraint.
3) It is also difficult to continue the hospitalization treatment by psychiatric specialty treatment or medication.
(11) Patients with pulmonary fibrosis and interstitial pneumonia
(12) With active double cancer
Active cancer refers to simultaneous double cancer and metachronous double cancer with a disease-free period of 5 years or less. Or, currently, have active treatment. However, lesions equivalent to Carcinoma in situ in the cervix, stomach, and large intestine that are judged to be cured by local treatment, those that respond to stable breast cancer, prostate cancer, or endocrine therapy are not included in double cancer.
(13) Pregnant and nursing women
(14) Allotransplantation, relapsed patients after autologous transplantation
(15) Patients who are unable to follow treatment, examination or follow-up by this study treatment or who are not willing to do so and who are judged by the principal investigator or research doctor
(16) Patients who do not agree to PML-RARA drug resistance gene mutation analysis and quantification of PML-RARA fusion gene transcript

Related Information

• Primary Sponsor: Kiguchi Toru