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Long-term Safety Study of Arsenic Trioxide in Newly Diagnosed, Low-to-intermediate Risk Acute Promyelocytic Leukemia (APL0618)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03751917
Recruitment Status : Recruiting
First Posted : November 23, 2018
Last Update Posted : October 8, 2020
Information provided by (Responsible Party):
Gruppo Italiano Malattie EMatologiche dell'Adulto

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.

Condition or disease Intervention/treatment
Acute Promyelocytic Leukemia Drug: Arsenic Trioxide

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.

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Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Cohort
Time Perspective: Other
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)
Actual Study Start Date : April 14, 2020
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : December 2024

Group/Cohort Intervention/treatment
APL patients
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
This is an observational study. Patients who have received or are receiving all trans retinoic acid (ATRA) + Arsenic Trioxide will be followed and analyzed.
Other Name: ATRA+ATO

Primary Outcome Measures :
  1. Number of grade III/IV (Common Terminology Criteria for Adverse Events (CTCAE) v4.03) adverse events of special interest (AESI). [ Time Frame: At a maximum of 5 years from study entry ]
    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).

Secondary Outcome Measures :
  1. Number of unexpected serious adverse events (SAEs). [ Time Frame: At a maximum of 5 years from study entry ]
    Including grading and relationship as documented in the study.

  2. Number of patients developing secondary malignancies. [ Time Frame: At a maximum of 5 years from study entry ]
  3. Number of patients developing therapy-related myelodysplastic syndrome (tMDS). [ Time Frame: At a maximum of 5 years from study entry ]
  4. Number of patients developing acute myeloid leukemia (tAML). [ Time Frame: At a maximum of 5 years from study entry ]
  5. Number of patients who die. [ Time Frame: At a maximum of 5 years from study entry ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

The Source Population for the study is patients included in existing multinational disease registries for APL in Europe. APL registries collect real-world data on APL demographics and provide information on disease characteristics, treatment patterns and long-term effects. Participating physicians are not subject to any instructions with regard to the diagnosis and therapy of their patients. All patient treatment is carried out within routine clinical practice at the discretion of the physician and according to existing treatment guidelines.

Data will be extracted from the registries for all patients meeting the above inclusion and exclusion criteria to provide the study population.


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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03751917

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Contact: Paola Fazi +39 0670390514
Contact: Enrico Crea +39 0670390514

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Sponsors and Collaborators
Gruppo Italiano Malattie EMatologiche dell'Adulto
Additional Information:
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Responsible Party: Gruppo Italiano Malattie EMatologiche dell'Adulto Identifier: NCT03751917    
Other Study ID Numbers: APL0618
First Posted: November 23, 2018    Key Record Dates
Last Update Posted: October 8, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Gruppo Italiano Malattie EMatologiche dell'Adulto:
Acute promyelocytic leukemia
Arsenic trioxide
Additional relevant MeSH terms:
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Leukemia, Promyelocytic, Acute
Neoplasms by Histologic Type
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Arsenic Trioxide
Antineoplastic Agents