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JOURNAL ONKOLOGIE – STUDIE

Treatment Study for Children and Adolescents With Acute Promyelocytic Leukemia

Rekrutierend

NCT-Nummer:
NCT04793919

Studienbeginn:
Oktober 2019

Letztes Update:
11.03.2021

Wirkstoff:
Mylotarg, Arsenic trioxide, all-trans retinoic acid

Indikation (Clinical Trials):
Leukemia, Leukemia, Promyelocytic, Acute

Geschlecht:
Alle

Altersgruppe:
Alle

Phase:
Phase 2

Sponsor:
Associazione Italiana Ematologia Oncologia Pediatrica

Collaborator:
-

Studienleiter

Fanco Locatelli, Prof
Principal Investigator
Dept. of Pediatric Hematology Oncology - Bambino Gesù Children's Hospital Rome

Kontakt

Studienlocations
(3 von 31)

Universitätsklinikum Essen (AöR) Zentrum für Kinder-und Jugendmedizin Klinik für Kinderheilkunde III
45147 Essen
(Nordrhein-Westfalen)
GermanyNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Dirk Reinhardt, Prof
Phone: 49-(0)201 1723-3784
E-Mail: Dirk.Reinhardt@uk-essen.de
» Ansprechpartner anzeigen
Hôpital Universitaire des Enfants Reine Fabiola (Huderf)
1020 Brussels
BelgiumNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Laurence Dedeken, MD
Phone: +324772678
E-Mail: laurence.dedeken@huderf.be
» Ansprechpartner anzeigen
Hôpital des Enfants
33076 Bordeaux-Cedex
FranceNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Stéphane Ducassou, MD
Phone: 0557820440
E-Mail: stephane.ducassou@chu-bordeaux.fr

Sophie REGUEME, MD
Phone: 0557821067
E-Mail: sophie.regueme@chu-bordeaux.fr
» Ansprechpartner anzeigen
Rappaport Children'S Hospital, Rambam Health Care Campus
Haifa
IsraelNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
NIRA ARAD-COHEN, MD
Phone: +972-50-206-1181
E-Mail: n_arad-cohen@rambam.health.gov.il
» Ansprechpartner anzeigen
AOU Policlinico Dipartimento di Pediatria
70124 Bari
ItalyNoch nicht rekrutierend» Google-Maps
Ospedale Pediatrico Microcitemico "A.Cau", Az.Ospedaliera Brotzu - SC Oncoematologia Ped. e Patologia della coagulazione
09121 Cagliari
ItalyNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Rosamaria Mura, Dr
» Ansprechpartner anzeigen
Policlinico Umberto I Università "LA Sapienza" - Dip. Biotecnologie cellulari ed ematologia UOS Ematologia Pediatrica
00161 Roma
ItalyNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Anna Maria Testi, Dr
» Ansprechpartner anzeigen
Childrens hematology and oncology Uppsala University
.O. Box 256, SE-751 05 Uppsala
SwedenNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Josefine Palle, MD
E-Mail: josefine.palle@akademiska.se
» Ansprechpartner anzeigen
Alle anzeigen

Studien-Informationen

Detailed Description:

Acute promyelocytic leukemia (APL) in children has become a highly curable disease with the

combination of all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy with an

overall remission rates equal to or higher than 98% and cure rates now exceeding 80% 1-9.

Based on data coming from adults indicating that at least standard-risk APL patients may be

cured without chemotherapy (i.e., with a treatment combining arsenic trioxide (ATO) and ATRA

only) 10-12, this ICC APL 02 study was designed with the aim of validating the efficacy of a

treatment combining:

- ATO and ATRA in newly diagnosed APL standard-risk (SR) children and adolescents and

- ATO, ATRA and gemtuzumab ozogamicin (GO) in newly diagnosed APL high-risk (HR) children

and adolescents.

Following one induction course of treatment combining ATO and ATRA +/- GO depending on risk

stratification, patients will receive 4 ATO/ATRA based consolidation blocks. This is the

first pediatric trial delivering a non-chemotherapy-based treatment for children with APL,

being the whole treatment based on the use of ATRA, ATO (and GO in HR patients). The aim of

the study is to demonstrate at least an equivalent efficacy and safety of this treatment not

containing cytostatic agents compared to the standard protocols combining ATRA and

chemotherapy (i.e. ICC APL Study 01).

The trial is open to all patients with a diagnosis of acute promyelocytic leukemia (APL) who

are PCR-positive for the PML-RARα transcript and less than 18 years of age.

This will be an international study, comprising the most important pediatric European groups,

expecting to recruit 46 and 43 patients in SR and HR arms, respectively, in 3 years. The

duration of study recruitment will be 36 months with a minimum follow-up per patient of 2

years.

The evaluation of morphological CR will be carried out after induction therapy, prior to the

first block of consolidation therapy. MRD results after induction will not have an impact on

subsequent therapy. By contrast, MRD results after the third consolidation course will

influence the subsequent treatment, MRD-positive patients being eligible to rescue treatment,

including hematopoietic stem cell transplantation (HSCT). BM aspirates will be repeated after

the end of therapy, and 3 months, 6 months, 9 months and 12 months after treatment

discontinuation.

This is a collaborative international study in APL in children and adolescents aimed at

providing information about procedures for the entry, treatment and follow-up of pediatric

patients with APL. It is not intended that this document be used as an aide-memoir or guide

for the treatment of other patients. Every care has been taken in its drafting, but

corrections and amendments may be necessary. Before entering patients into the study,

clinicians must ensure that the study has received clearance from their Local Research Ethics

Committee and any other necessary body.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Newly diagnosed APL confirmed by the presence of PML/RARα fusion gene

- Age <18 years

- Written informed consent by parents or legal guardians

Exclusion Criteria:

- Patients with a clinical diagnosis of APL but subsequently found to lack PML/RARα

rearrangement should be withdrawn from the study and treated on an alternative

protocol

- Significant liver dysfunction (bilirubin serum levels >3 mg/dL, ALT/AST serum levels

greater than 5 times the normal values)

- Creatinine serum levels >2 times the normal value for age

- Significant arrhythmias, EKG abnormalities (*see below), other cardiac

contraindications (L-FEV <50% or LV-FS <28%)

- Neuropathy

- Concurrent active malignancy

- Uncontrolled life-threatening infections

- Pregnant or lactating female

- Patients who had received alternative therapy (APL not initially suspected; ATRA

and/or ATO not available

Studien-Rationale

Primary outcome:

1. Event Free Survival (EFS) probability (Time Frame - 3 years):
SR patients: To evaluate the efficacy in terms of event-free survival of a treatment combining arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) in newly diagnosed APL standard-risk children and adolescents HR patients: To evaluate the efficacy in terms of event-free survival of a treatment combining arsenic trioxide (ATO), all-trans retinoic acid (ATRA) and gemtuzumab ozogamicin (GO) in newly diagnosed APL high-risk children and adolescents



Secondary outcome:

1. Rate of hematological CR/CRi after induction (Time Frame - 5 years):
To evaluate the rate of hematological Complete Remission (CR) (defined as bone marrow regenerating normal hematopoietic cells and containing < 5% blast cells by morphology, with ANC in peripheral blood > 1.0 x 10^9/L and platelet count > 100 x 10^9/L) and Complete Remission with incomplete hematologic recovery (CRi) (defined as CR except that peripheral blood neutrophils and/or platelets do not meet the criteria as defined above) after induction therapy.

2. Rate of molecular CR/CRi after induction (Time Frame - 5 years):
To evaluate the rate of molecular CR/CRi (defined as the absence of PML/RARα fusion transcript in bone marrow assessed by RQ-PCR, with an assay sensitivity of at least 10^-4).

3. Rate of early death during induction (Time Frame - 5 years):
To evaluate the rate of early death during induction (defined as any death occurring within 14 days from diagnosis from any cause).

4. Probability of overall survival (OS) at 3 years (Time Frame - 3 years):
To evaluate the rate of overall survival

5. Cumulative incidence of relapse (CIR) at 3 years (Time Frame - 3 years):
To evaluate the cumulative incidence of hematological relapse (defined as reappearance of promyeloblasts/abnormal promyelocytes > 5% in the bone marrow) and molecular relapse (defined as reappearance of PML/RARα fusion transcript in two successive samples taken at least 2 weeks apart in patients previously in molecular remission).

6. Incidence of hematological and non-hematological toxicity (Time Frame - 5 years):
Incidence of treatment-related hematological and non-hematological toxicity assessed by CTCAE v4.0

7. Rate of molecular remission after 3 consolidation cycles (Time Frame - 5 years):
To evaluate the rate of molecular remission (defined as the absence of PML/RARα fusion transcript in bone marrow assessed by RQ-PCR, with an assay sensitivity of at least 10^-4) after 3 consolidation cycles.

8. Assessment of PML/RARα transcription level reduction during treatment (Time Frame - 5 years):
To evaluate the reduction of PML/RARα fusion transcript in bone marrow by means of RQ-PCR during treatment.

9. Pediatric Quality of Life assessment (Time Frame - 5 years):
Pediatric Quality of life assessed by PedsQoL questionnaire, in the questionnaire there is a list of things that might be a problem for the child. The minimum value is 0 (never a problem) - maximum value 4 (almost always problem)

10. Total hospitalization days during therapy (Time Frame - 5 years):
Number of total hospitalization days during the treatment.

Studien-Arme

  • Active Comparator: Standard Risk (SR)
    Patient with APL and WBC less than 10x10e9/L at presentation before start treatment
  • Experimental: High Risk (HR)
    Patient with APL, with the highest pre-treatment WBC count equal to or greater than 10x10e9/L at presentation

Geprüfte Regime

  • Mylotarg (GO):
    See the protocol
  • Arsenic Trioxide (ATO):
    See the protocol
  • All-trans retinoic acid (ATRA):
    See the protocol

Quelle: ClinicalTrials.gov


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