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

  • STATUS
    Recruiting
  • End date
    Jan 23, 2022
  • participants needed
    280
  • sponsor
    Technische Universität Dresden
Updated on 23 January 2021
Investigator
Uwe Platzbecker, MD
Primary Contact
PETHEMA study group (8.1 mi away) Contact
+7 other location
hysterectomy
myeloid leukemia
methotrexate
cytarabine
tretinoin
monoclonal antibody
arsenic
serum bilirubin
consolidation therapy
mitoxantrone
idarubicin
acute promyelocytic leukemia
anthracyclines
secondary mds

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/RAR) 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.

Details
Condition Acute myeloid leukemia, Acute Promyelocytic Leukemia, Acute Myelogenous Leukemia (AML)
Treatment methotrexate, cytarabine, Mitoxantrone, Mercaptopurine, Idarubicin, Arsenic trioxide, tretinoin
Clinical Study IdentifierNCT02688140
SponsorTechnische Universität Dresden
Last Modified on23 January 2021

Eligibility

Yes No Not Sure

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 mol/l)
Serum creatinine 3.0 mg/dl ( 260 mol/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
Clear my responses

How to participate?

Step 1 Connect with a site
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar
Name

Primary Contact

site
Name

0/250
Preferred Language
Other Language
Please verify that you are not a bot.

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note