Long-term Safety Study of Arsenic Trioxide in Newly Diagnosed, Low-to-intermediate Risk Acute Promyelocytic Leukemia

Study Overview
=================
Brief Summary
-----------------
The therapeutic advantage of the association of ATRA + Arsenic Trioxide is more favorable and manageable as compared to ATRA + chemotherapy. Nevertheless, at present, there is not enough information on the incidence of long-term side effects. This study, as well as other similar studies conducted around Europe, will focus on following patients treated with this therapy on a long-term basis. Once all studies in Europe will be concluded, all data will be analyzed together.

Detailed Description
-----------------
Considering the clear therapeutic advantage associated with ATRA+ATO combination therapy and the more favorable and overall manageable safety profile compared to ATRA+chemotherapy, the benefits of the combination in the first-line indication do appear to overweigh the risks. However, no information regarding the actual adverse event (AE) incidence and the long-term toxicity of ATRA+ATO is available at present and therefore, as a postmarketing commitment, TEVA (the Company holding the Marketing Authorisation of Trisenox® (Arsenic trioxide)) is setting up a long-term safety cohort study of Trisenox in newly diagnosed low- to intermediate-risk APL patients retrospectively analyzing data from APL disease registries all around Europe. As a result, this observational study is part of the retrospective PASS Study (A Post-Authorisation Long-Term Retrospective Safety Cohort Study of Arsenic Trioxide in First Line Low-to Intermediate-Risk Acute Promyelocytic Leukaemia Patients) that will use data from multinational APL disease registries in Europe. The present study will focus on Italian patients.

Official Title
-----------------
A Long-Term Retrospective and Prospective Safety Study of Arsenic Trioxide in Patients With Newly Diagnosed, Low- to Intermediate-Risk Acute Promyelocytic Leukemia (APL)

Conditions
-----------------
Acute Promyelocytic Leukemia

Intervention / Treatment
-----------------
* Drug: Arsenic Trioxide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: APL diagnosis based on cytological criteria and confirmed by the presence of the (15;17) translocation and/or the presence of the PML/RARA rearrangement (with the determination of the breakpoint subtype). Newly diagnosed low- to intermediate-risk APL (white blood cells [WBC] count ≤10x103/µL) First line treatment with ATRA+ATO Aged 18 years or above Signed informed consent, if applicable Exclusion Criteria: High risk APL (WBC count > 10x103/µL) APL relapse

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| APL patients<br>The study will be conducted using multinational data from disease registries for APL. The study participants will consist of patients with newly diagnosed, low-to intermediate-risk APL. | Drug: Arsenic Trioxide<br>* This is an observational study. Patients who have received or are receiving all trans retinoic acid (ATRA) + Arsenic Trioxide will be followed and analyzed.<br>* Other names: ATRA+ATO;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of grade III/IV (Common Terminology Criteria for Adverse Events (CTCAE) v4.03) adverse events of special interest (AESI). | AESI are, among others: differentiation syndrome, creatinine, bilirubin, neurotoxicity, aspartate amino transferase/alanine amino transferase (ASAT/ALAT) ratio, haemorrhage, sepsis, QTc prolongation, cardiac events including congestive heart failure (CHF). | At a maximum of 5 years from study entry | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of unexpected serious adverse events (SAEs). | Including grading and relationship as documented in the study. | At a maximum of 5 years from study entry | 
| Number of patients developing secondary malignancies. |  | At a maximum of 5 years from study entry | 
| Number of patients developing therapy-related myelodysplastic syndrome (tMDS). |  | At a maximum of 5 years from study entry | 
| Number of patients developing acute myeloid leukemia (tAML). |  | At a maximum of 5 years from study entry | 
| Number of patients who die. |  | At a maximum of 5 years from study entry | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Acute promyelocytic leukemia, Adults, Arsenic trioxide