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Acute Promyelocytic LeukemiaPhase 3TUD-APOLLO-064NCT02688140

Study for Patients With Newly Diagnosed, High-risk Acute Promyelocytic Leukemia

A Phase 3 study testing Arsenic trioxide, Idarubicin and Cytarabine in people with Acute Promyelocytic Leukemia, run by Technische Universität Dresden at 8 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Acute promyelocytic leukemia (APL) is a rare subtype of acute myeloid leukemia (AML) characterized by consistent clinical, morphologic, and genetic features. According to the FAB classification APL is designated as"M3 leukemia" and assigned to the WHO defined type of AML with recurrent cytogenetic abnormalities… Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Acute Promyelocytic Leukemia
What is being tested?
Arsenic trioxide, Idarubicin and Cytarabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
133 participants
Where
8 sitesin 5 countries
Study dates
Jun 2016to 20 Jan 2025
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Informed consent
  • Women or men with a newly diagnosed APL by cytomorphology, confirmed by molecular analysis*
  • Age ≥ 18 and ≤ 65 years
  • ECOG performance status 0-3
  • WBC at diagnosis > 10 GPt/l
  • Serum total bilirubin ≤ 3.0 mg/dl (≤ 51 µmol/l)
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  • Serum creatinine ≤ 3.0 mg/dl (≤ 260 µmol/l)
  • Women must fulfill at least one of the following criteria in order to be eligible for trial inclusion:
  • Post-menopausal (12 months of natural amenorrhea or 6 months of amenorrhea with Serum FSH > 40 U/ml)
  • Postoperative (i.e. 6 weeks) after bilateral ovariectomy with or without hysterectomy
  • Continuous and correct application of a contraception method with a Pearl Index of <1% (e.g. implants, depots, oral contraceptives, -intrauterine device - IUD)
  • Sexual abstinence
  • Vasectomy of the sexual partner
  • The confirmation of diagnosis at genetic level (microspeckled PML nuclear distribution by PGM3 monoclonal antibody and/or PML/RARa fusion by RT-PCR or fluorescence in situ hybridization (FISH) and/or demonstration of t(15;17) at karyotyping) will be mandatory for patient eligibility. However, in order to avoid delay in treatment initiation, patients can be randomized on the basis of morphologic diagnosis only and before the results of genetic tests are available

Who cannot join

  • Patients who are not eligible for chemotherapy as per discretion of the treating physician
  • APL secondary to previous radio- or chemotherapy for non-APL disease
  • Other active malignancy at time of study entry (exception: basal-cell carcinoma)
  • Lack of diagnostic confirmation at genetic level
  • Significant arrhythmias, ECG abnormalities:
  • Congenital long QT syndrome;
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  • History or presence of significant ventricular or atrial tachyarrhythmia;
  • Clinically significant resting bradycardia (<50 beats per minute)
  • QTc >500msec on screening ECG for both genders (using the QTcF formula detailed on protocol)
  • Right bundle branch block plus left anterior hemiblock, bifascicular block
  • Other cardiac contraindications for intensive chemotherapy (L-VEF <50%)
  • Uncontrolled, life-threatening infections
  • Severe non controlled pulmonary or cardiac disease
  • Severe hepatic or renal dysfunction
  • HIV and/or active hepatitis C infection
  • Pregnant or breast-feeding patients
  • Allergy to trial medication or excipients in study medication
  • Substance abuse; medical, psychological or social conditions that may interfere with the patients participation in the study or evaluation of the study results
  • Use of other investigational drugs at the time of enrolment or within 30 days before study entry

Trial locations and contacts

8 sites in 5 countries.

8 sites in 5 countries

Germany4 sites

  • AML-CG study group

    All Participating Sites

  • AML-SG study group

    All Participating Sites

  • OSHO study group

    All Participating Sites

  • SAL study group

    All Participating Sites

Other trials in Germany

France1 site

  • French-Belgian-Swiss APL study group

    All Participating Sites

Other trials in France

Italy1 site

  • GIMEMA study group

    All Participating Sites

Other trials in Italy

Netherlands1 site

  • HOVON study group

    All Participating Sites

Other trials in Netherlands

Spain1 site

  • PETHEMA study group

    All Participating Sites

Other trials in Spain

About this study

Official title: A Randomized Phase III Study to Compare Arsenic Trioxide (ATO) Combined to ATRA and Idarubicin Versus Standard ATRA and Anthracyclines-based Chemotherapy (AIDA Regimen) for Patients With Newly Diagnosed, High-risk Acute Promyelocytic Leukemia

Acute promyelocytic leukemia (APL) is a rare subtype of acute myeloid leukemia (AML) characterized by consistent clinical, morphologic, and genetic features. According to the FAB classification APL is designated as"M3 leukemia" and assigned to the WHO defined type of AML with recurrent cytogenetic abnormalities, "acute promyelocytic leukemia with t(15;17)(q22;q12), (PML/RARα) and variants".

Despite the dramatic progress achieved in frontline therapy of APL with ATRA plus anthracycline-based regimens, relapses still occur in approximately 20% of patients. Moreover, these regimens are associated with significant toxicities due to severe myelosuppression frequently associated with life-threatening infections and potentially serious late effects including development of secondary MDS/AML. In a recent randomized clinical trial in low/intermediate-risk APL (WBC ≤ 10 GPt/l APL0406 trial) a combination of arsenic trioxide (ATO) and ATRA has been shown to result into better survival with significantly lower toxicity rates compared to the standard ATRA + idarubicin (AIDA) therapy. Inspired by the results of this trial the investigators intend to perform a randomized study in high-risk APL (WBC at diagnosis > 10 GPt/l) comparing standard AIDA-based treatment with ATO/ATRA combination including low-doses idarubicin during induction. The investigators propose a modified ATO/ATRA protocol with the addition of two doses of IDA (50% compared to standard AIDA induction) for induction because of the anticipated need of adding anthracyclines to control hyperleukocytosis and to achieve long-term disease control in this high-risk APL population. This is followed by 4 cycles of ATO/ATRA consolidation therapy. As in the APL0406 study for low/intermediate-risk patients the investigators expect less severe hematologic toxicity and treatment-related mortality resulting in an improved outcome for patients in the experimental arm. Furthermore, from the start of consolidation, these patients (in contrast to the standard arm) can be treated on an outpatient basis, which is also considered to be associated with an improved quality of life. The study will be conducted as a European intergroup study.

Being tested
Arsenic trioxide, Idarubicin, Cytarabine, Tretinoin, Mitoxantrone
Keywords
APL, acute promyelocytic leukemia (M3), high-risk acute promyelocytic leukemia (APL/AML M3), acute myeloid leukemia with t(15;17)(q22;q12), newly diagnosed, high-risk
Medical subject headings
Leukemia, Promyelocytic, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Arsenic trioxideDrug

    Also called ATO, Trisenox (R), As2O3

  • IdarubicinDrug

    Also called IDA

  • CytarabineDrug

    Also called Ara-C

  • TretinoinDrug

    Also called all-trans retinoic acid, ATRA

  • MitoxantroneDrug

    Also called MTZ

  • MercaptopurineDrug

    Also called 6-Mercaptopurine, 6-MP

  • MethotrexateDrug

    Also called MTX

Study groups in NCT02688140
Study groupRoleWhat they receive
Arm AExperimentalInduction therapy: Patients receive idarubicin i.v. over 20 minutes on day 1 and 3, oral tretinoin twice daily on day 1-28 (max. up to day 60) and arsenic trioxide i.v. over 2 hours on day 5-28 (max. up to day 60). In case of morphological CR and regenerated blood counts, consolidation therapy should be started within 2-4 weeks after documented CR. Consolidation therapy: Patients receive oral tretinoin twice daily on day 1-14. Treatment with tretinoin repeats every 4 weeks for up to 7 courses. Patients also receive arsenic trioxide i.v. over 2 hours on days 1-5 in week 1-4. Treatment with arsenic trioxide repeats every 8 weeks for up to 4 courses.
Receives: Drug: Arsenic trioxide; Drug: Idarubicin; Drug: Tretinoin
Arm B (standard chemotherapy)Active comparatorInduction therapy: Patients receive idarubicin i.v. over 20 minutes on day 1,3,5 and 7, oral tretinoin twice daily on day 1-28 (max. up to day 60). In case of morphological CR and regenerated blood counts, consolidation therapy should be started within 2-4 weeks after documented CR. Consolidation I: IDA 5 mg/m2 i.v. day 1-4 Ara-C 1000 mg/m2/3h i.v. day 1-4 ATRA 45 mg/m2 p.o. day 1-15 Consolidation II: MTZ 10 mg/m2 i.v. day 1-5 ATRA 45 mg/m2 p.o. day 1-15 Consolidation III: IDA 12 mg/m2 i.v. day 1 Ara-C 150 mg/m2 every 8h i.v. day 1-5 ATRA 45 mg/m2 p.o. day 1-15 Maintenance (duration 7 cycles = 2 years; one cycle lasts 106 days): 6-MP 50 mg/m2 p.o. Cycle 1-7: day 1-91 (followed by 15 days of ATRA on days 92-106) MTX 15mg/m2 i.m./p.o. Cycle 1-7: once weekly for 91 days (followed by 15 days of ATRA on days 92-106) ATRA 45 mg/m2 p.o. Cycle 1-6: day 92-106 Cycle 7: without ATRA Administration (treatment break of 6-MP and MTX during ATRA administration)
Receives: Drug: Idarubicin; Drug: Cytarabine; Drug: Tretinoin; Drug: Mitoxantrone; Drug: Mercaptopurine; Drug: Methotrexate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Event-free survival

    events are: no achievement of haematological complete remission after induction therapy; no achievement of molecular remission after the last consolidation course; relapse; death including early death or development of secondary AML or MDS

    Measured: From date of randomization until the date of first documented event, assessed up to 66 months

Secondary outcomes (11)

  1. Rate of hematological complete remission

    Measured: up to 60 days, from date of randomization until end of induction therapy

  2. Rate of early death within 30 days after randomization

    Measured: up to 30 days after randomization

  3. Rate of overall survival (OS)

    Measured: at 2 years

  4. Rate of cumulative incidence of secondary MDS or AML

    Measured: assessed up to 66 months, from date of randomization until occurance of secondary AML or MDS

  5. Rate of cumulative incidence of relapse (CIR)

    Measured: at 2 years

  6. Incidence of hematological and non-hematological toxicity

    Measured: assessed up to 30 months after randomization

  7. Rate of molecular remission after the last consolidation cycle

    Measured: up to 256 days after randomization

  8. Assessment of acute promyelocytic leukemia/RARa transcript level reduction after induction therapy until end of study

    Measured: assessed up to 30 months after randomization

  9. Quality of Life at the end of induction therapy until the end of study

    Measured: assessed up to 30 months after randomization

  10. To investigate differences in the immune reconstitution between the two arms

    Measured: assessed up to 30 months after randomization

  11. Total hospitalization days during therapy

    Measured: assessed up to 30 months after randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Feb 2016 (estimated)
  2. Study startJun 2016
  3. Primary completion20 Jan 2025
  4. Study completion20 Jan 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
133 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02688140
Sponsor's protocol ID
TUD-APOLLO-064
Acronym
TUD-APOLLO-064
Status last verified
May 2026
First submitted
11 Feb 2016
Last updated
29 May 2026
Results posted
No
Data monitoring committee
Yes

Publications

  • Platzbecker U, Ades L, Montesinos P, Ammatuna E, Fenaux P, Baldus C, Bernardi M, Berthon C, Bocchia M, Bonmati C, Borlenghi E, Bornhauser M, Carp D, Chantepie S, Crea E, Divona M, Dohner H, Ehninger G, Esteve Reyner J, Frayfer J, Garrido Diaz A, Gil C, Guarnera L, Hamm AF, Heiblig M, Heidenreich D, Kramer AJ, Ledoux MP, Lunghi M, Mancini V, Metzeler K, Miggiano MC, Muller-Tidow C, Peterlin P, Piciocchi A, Rieger K, Rollig C, Rossi G, Sanz MA, Serve H, Sohne M, Spiekermann K, Tavernier-Tardy E, Thiede C, Vives Polo S, Vogel W, Zappasodi P, Ziller-Walter P, Voso MT; SAL, AMCL-CG, AML-SG, OSHO, PETHEMA, HOVON and GIMEMA study groups. Arsenic Trioxide and All-Trans Retinoic Acid Combination Therapy for the Treatment of High-Risk Acute Promyelocytic Leukemia: Results From the APOLLO Trial. J Clin Oncol. 2025 Oct 10;43(29):3160-3169. doi: 10.1200/JCO-25-00535. Epub 2025 Aug 18.

    PubMed 40825164

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Arsenic trioxide, Idarubicin and Cytarabine in people with Acute Promyelocytic Leukemia, run by Technische Universität Dresden at 8 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Germany, France, Italy, Netherlands, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event-free survival (time frame: From date of randomization until the date of first documented event, assessed up to 66 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02688140, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 May 2026.

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