ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 93 of 253 for:    IDARUBICIN

Study for Patients With Newly Diagnosed, High-risk Acute Promyelocytic Leukemia (TUD-APOLLO-064)

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.
ClinicalTrials.gov Identifier: NCT02688140
Recruitment Status : Recruiting
First Posted : February 23, 2016
Last Update Posted : June 21, 2018
Sponsor:
Collaborators:
Gruppo Italiano Malattie EMatologiche dell'Adulto
Groupe Francophone des Myelodysplasies
Haemato Oncology Foundation for Adults in the Netherlands
Programa para el Tratamiento de Hemopatías Malignas
German Federal Ministry of Education and Research
Teva Pharmaceuticals Europe
Information provided by (Responsible Party):
Technische Universität Dresden

Brief 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, "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.


Condition or disease Intervention/treatment Phase
Acute Promyelocytic Leukemia Drug: Arsenic trioxide Drug: Idarubicin Drug: Cytarabine Drug: Tretinoin Drug: Mitoxantrone Drug: Mercaptopurine Drug: Methotrexate Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 280 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : June 2016
Estimated Primary Completion Date : November 2021
Estimated Study Completion Date : January 2022


Arm Intervention/treatment
Experimental: Arm A

Induction 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.

Drug: Arsenic trioxide
Other Names:
  • ATO
  • Trisenox (R)
  • As2O3

Drug: Idarubicin
Other Name: IDA

Drug: Tretinoin
Other Names:
  • all-trans retinoic acid
  • ATRA

Active Comparator: Arm B (standard chemotherapy)

Induction therapy: Patients receive idarubicin i.v. over 20 minutes on day 1,3,5 and 7 and 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 therapy: Patients receive oral tretinoin twice daily on day 1-45, idarubicin i.v. over 20 minutes on day 1-4 and day 31, cytarabine i.v. over 3 hours on day 1-4, over 8 hours on day 31-35, mitoxantrone i.v. over 30 minutes on day 16-20.

Maintenance therapy (only for PML-RARa negative patients): Patients receive oral mercaptopurine once daily and methotrexate i.m./p.o. once weekly for 3 months. Treatment with mercaptopurine and methotrexate repeats every 3 months for 7 courses. After completion of course 1 of mercaptopurine and methotrexate, patients receive oral tretinoin once daily on days 1-15. Treatment with tretinoin repeats every 3 months for 6 courses

Drug: Idarubicin
Other Name: IDA

Drug: Cytarabine
Other Name: Ara-C

Drug: Tretinoin
Other Names:
  • all-trans retinoic acid
  • ATRA

Drug: Mitoxantrone
Other Name: MTZ

Drug: Mercaptopurine
Other Names:
  • 6-Mercaptopurine
  • 6-MP

Drug: Methotrexate
Other Name: MTX




Primary Outcome Measures :
  1. Event-free survival [ Time Frame: From date of randomization until the date of first documented event, assessed up to 66 months ]
    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


Secondary Outcome Measures :
  1. Rate of hematological complete remission [ Time Frame: up to 60 days, from date of randomization until end of induction therapy ]
  2. Rate of early death within 30 days after randomization [ Time Frame: up to 30 days after randomization ]
  3. Rate of overall survival (OS) [ Time Frame: at 2 years ]
  4. Rate of cumulative incidence of secondary MDS or AML [ Time Frame: assessed up to 66 months, from date of randomization until occurance of secondary AML or MDS ]
  5. Rate of cumulative incidence of relapse (CIR) [ Time Frame: at 2 years ]
  6. Incidence of hematological and non-hematological toxicity [ Time Frame: assessed up to 30 months after randomization ]
  7. Rate of molecular remission after the last consolidation cycle [ Time Frame: up to 256 days after randomization ]
  8. Assessment of acute promyelocytic leukemia/RARa transcript level reduction after induction therapy until end of study [ Time Frame: assessed up to 30 months after randomization ]
  9. Quality of Life at the end of induction therapy until the end of study [ Time Frame: assessed up to 30 months after randomization ]
  10. To investigate differences in the immune reconstitution between the two arms [ Time Frame: assessed up to 30 months after randomization ]
  11. Total hospitalization days during therapy [ Time Frame: assessed up to 30 months after randomization ]


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.


Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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)
  • 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

Exclusion Criteria:

  • 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;
  • 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

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 ClinicalTrials.gov identifier (NCT number): NCT02688140


Contacts
Contact: Uwe Platzbecker, Prof. Dr. +49 351 458 ext 3192 uwe.platzbecker@uniklinikum-dresden.de
Contact: Michaela Sauer +49 351 458 ext 3192 michaela.sauer@uniklinikum-dresden.de

Locations
France
French-Belgian-Swiss APL study group Not yet recruiting
Multiple Locations, France
Contact: Pierre Fenaux, Prof. Dr.       pierre.fenaux@avc.ap-hop-paris.fr   
Contact: Lionel Ades, Dr.       lionel.ades@sls.aphp.fr   
Germany
AML-CG study group Recruiting
Multiple Locations, Germany
Contact: Eva Lengfelder, Prof. Dr.       Eva.Lengfelder@umm.de   
AML-SG study group Recruiting
Multiple Locations, Germany
Contact: Richard F. Schlenk, Prof. Dr.       Richard.Schlenk@uniklinik-ulm.de   
OSHO study group Recruiting
Multiple Locations, Germany
Contact: Dietger Niederwieser, Prof. Dr.       Dietger.Niederwieser@medizin.uni-leipzig.de   
SAL study group Recruiting
Multiple Locations, Germany
Contact: Uwe Platzbecker, Prof. Dr.    +49 351 458 ext 3192    uwe.platzbecker@uniklinikum-dresden.de   
Contact: Michaela Sauer    +49 351 458 ext 3192    michaela.sauer@uniklinikum-dresden.de   
Italy
GIMEMA study group Not yet recruiting
Multiple Locations, Italy
Contact: Francesco Lo-Coco, Prof. Dr.       Francesco.lo.coco@uniroma2.it   
Contact: Fabio Efficace, Dr.       f.efficace@gimema.it   
Netherlands
HOVON study group Not yet recruiting
Multiple Locations, Netherlands
Contact: Edo Vellenga, Prof. Dr.       e.vellenga@umcg.nl   
Spain
PETHEMA study group Not yet recruiting
Multiple Locations, Spain
Contact: Miguel A. Sanz, Prof. Dr.       sanz_mig@gva.es   
Contact: Pau Montesinos, Prof. Dr.       montesinos_pau@gva.es   
Sponsors and Collaborators
Technische Universität Dresden
Gruppo Italiano Malattie EMatologiche dell'Adulto
Groupe Francophone des Myelodysplasies
Haemato Oncology Foundation for Adults in the Netherlands
Programa para el Tratamiento de Hemopatías Malignas
German Federal Ministry of Education and Research
Teva Pharmaceuticals Europe
Investigators
Principal Investigator: Uwe Platzbecker, Prof. Dr. Technische Universität Dresden (TUD)

Responsible Party: Technische Universität Dresden
ClinicalTrials.gov Identifier: NCT02688140     History of Changes
Other Study ID Numbers: TUD-APOLLO-064
First Posted: February 23, 2016    Key Record Dates
Last Update Posted: June 21, 2018
Last Verified: June 2018

Keywords provided by Technische Universität Dresden:
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

Additional relevant MeSH terms:
Idarubicin
Leukemia
Leukemia, Promyelocytic, Acute
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Methotrexate
Cytarabine
6-Mercaptopurine
Tretinoin
Mitoxantrone
Arsenic trioxide
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Antiviral Agents
Anti-Infective Agents