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Imfinzi NSCLC
Imfinzi NSCLC
JOURNAL ONKOLOGIE – STUDIE

Randomized Phase III Study of Intensive Chemotherapy With or Without Dasatinib (Sprycel™)

Rekrutierend

NCT-Nummer:
NCT02013648

Studienbeginn:
Juli 2014

Letztes Update:
04.06.2020

Wirkstoff:
Dasatinib, Cytarabine, Daunorubicin, Idarubicin

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

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
University of Ulm

Collaborator:
-

Studienleiter

Hartmut Doehner, Prof. Dr.
Principal Investigator
University of Ulm

Kontakt

Hartmut Doehner, Prof. Dr.
Kontakt:
Phone: 0049-731-500-
Phone (ext.): 45501
E-Mail: hartmut.doehner@uniklinik-ulm.de
» Kontaktdaten anzeigen
Peter Paschka, Dr.
Kontakt:
Phone: 0049-731-500
Phone (ext.): 45746
E-Mail: peter.paschka@uniklinik-ulm.de
» Kontaktdaten anzeigen

Studienlocations (3 von 53)

Universitätsklinikum Medizinische Klinik und Poliklinik
40001 Düsseldorf
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Ulrich Germing, Prof. Dr.

Mustafa Kondakci, Dr.
» Ansprechpartner anzeigen
Interdisziplinäres Brustzentrum am Klinikum Esslingen
Hirschlandstraße 97
73730 Esslingen am Neckar
(Baden-Württemberg)
DeutschlandRekrutierend» Google-Maps
Ansprechpartner:
Swen Wessendrof, PD Dr.
» Ansprechpartner anzeigen
Gemeinschaftspraxis Hämato-Onkologie im Caritas Krankenhaus
66822 Lebach
(Saarland)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Stephan Kremers, Dr. med.

Gero Leonhard-Helmschmidt, Dr.
» Ansprechpartner anzeigen
III. Medizinische Klinik und Poliklinik Universitätsmedizin der Johannes Gutenberg-Universität
55131 Mainz
(Rheinland-Pfalz)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Markus Radsak, PD Dr.

Thomas Kindler, PD Dr.
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Alle anzeigen

Studien-Informationen

Detailed Description:

This is a randomized phase III open-label, multicenter trial evaluating standard induction therapy (daunorubicin [DNR] and cytarabine [Ara-C]) and consolidation therapy (high-dose cytarabine [HDAC]) with or without dasatinib in adult patients with newly diagnosed CBF-AML; in the investigational arm, consolidation therapy is followed by a one-year maintenance therapy with dasatinib. Patients with molecular disease persistence or molecular relapse as assessed by quantitative RQ-PCR for the CBF fusion transcripts will be eligible for hematopoietic stem cell transplantation before overt hematologic relapse occurs. Primary endpoint is event-free survival.

AML patients will be assessed for the CBF fusion genes in one of two AMLSG central laboratories within 48 hours of diagnosis, and only patients with CBF-AML will be enrolled.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Core-binding factor (CBF) AML with molecular diagnosis of RUNX1-RUNX1T1 fusion transcript resulting from t(8;21)(q22;q22.1) (or a variant form) or of CBFB-MYH11 fusion transcript resulting from inv(16)(p13.1q22)/t(16;16)(p13.1;q22) as assessed in one of the central AMLSG reference laboratories (Ulm, Hannover)

- Age ≥ 18; there is no upper age limit

- No prior chemotherapy for leukemia except hydroxyurea for up to 5 days during the diagnostic screening phase

- Non-pregnant and non-nursing. Due to the unknown teratogenic potential of dasatinib in humans, pregnant or nursing patients may not be enrolled. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within a sensitivity of at least 25 mIU/mL with-in 72 hours prior to registration. Women of child-bearing potential must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control - one highly effective method (e.g., IUD, hormonal, tubal ligation, or partner's vasectomy), and one additional effective method (e.g., latex condom, diaphragm, or cervical cap) - AT THE SAME TIME, at least four weeks before she begins dasatinib therapy. "Women of childbearing potential" is defined as a sexually active mature woman who has not undergone a hysterectomy or who has had menses at any time in the preceding 24 consecutive months.

- Men must agree not to father a child and must use a latex condom during any sexual contact with women of childbearing potential while taking dasatinib and for 3 months after therapy is stopped, even if they have undergone a successful vasectomy.

- Signed written informed consent.

Exclusion Criteria:

- Performance status WHO >2

- Pulmonary edema and/or pleural/pericardial effusion within 14 days of day 1. If edema/effusion resolves to CTC Grade ≤1, patients can be treated with dasatinib.

- Patients with ejection fraction <50% by echocardiography within 14 days of day 1

- Organ insufficiency (creatinine >1.5x upper normal serum level; bilirubin, AST or AP >2.5x upper normal serum level; heart failure NYHA III/IV; severe obstructive or restrictive ventilation disorder)

- Uncontrolled infection

- Patients with a "currently active" second malignancy other than non-melanoma skin cancers. Patients are not considered to have a "currently active" malignancy, if they have completed therapy and are considered by their physician to be at less than 30% risk of relapse within one year.

- Severe neurological or psychiatric disorder interfering with ability of giving an informed consent

- Known positive for HIV, active HBV, HCV, or Hepatitis A infection

- Bleeding disorder independent of leukemia

- No consent for registration, storage and processing of the individual disease characteristics and course as well as information of the family physician and/or other physicians involved in the treatment of the patient about study participation.

- No consent for biobanking.

Studien-Rationale

Primary outcome:

1. Event-free Survival (Time Frame - 4 years):
To assess event-free survival (EFS) after intensive induction (daunorubicin and cytarabine) and consolidation (high-dose cytarabine) chemotherapy with or without dasatinib in patients with CBF-AML



Secondary outcome:

1. Cumulative incidence of relapse (CIR) (Time Frame - 4 years)

2. Cumulative incidence of death (CID) (Time Frame - 4 years)

3. overall survival (Time Frame - 4 years)

4. relapse-free survival (Time Frame - 4 years)

5. PIA analysis (Time Frame - 4 years):
Pharmacodynamic inhibition of KIT as assessed by the KIT plasma inhibitory assay (PIA)

6. toxicity (Time Frame - 7 months (standard arm) / 19 months (investigational arm)):
Type, frequency, severity (graded using the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version 4.03), timing and relatedness of non-hematologic toxicity observed during different treatment cycles.

Studien-Arme

  • Active Comparator: Standard arm
    Patients will receive induction therapy with daunorubicin 60 mg/m2/day administered on days 1-3 (when daunorubicin is not available due to supply shortage: Idarubicin 12mg²/day on days 1,3,5) and cytarabine 200 mg/m2/day administered by continuous IV infusion on days 1-7. Patients achieving PR only at the end of cycle 1 will receive a second induction cycle with daunorubicin 50 mg/m2/day (when daunorubicin is not available due to supply shortage: Idarubicin 10 mg²/day on days 1 and 3) administered on days 1-3 and cytarabine 200 mg/m2/day administered by cont. IV infusion daily on days 1-5. Patients will receive 4 cycles of consolidation therapy. Consolidation therapy consists of high-dose cytarabine 3 g/m2 (>60 years: 1 g/m2) q12h, days 1-3 administered intravenously over three hours. Follow-up period: There is no maintenance therapy in the standard arm. Patients will be closely followed, in particular for molecular disease persistence or molecular relapse.
  • Experimental: Investigational arm
    Patients will receive induction therapy with daunorubicin 60 mg/m2/day on days 1-3 (when daunorubicin is not available due to supply shortage: Idarubicin 12mg²/day on days 1,3,5) and cytarabine 200 mg/m2/day by cont. IV infusion on days 1-7. Patients will receive dasatinib 100 mg QD on days 8-21. Patients achieving PR only at the end of cycle 1 will receive a 2nd induction cycle with daunorubicin 50 mg/m2/day on days 1-3 (when daunorubicin is not available due to supply shortage: Idarubicin 10 mg²/day on days 1 and 3) and cytarabine 200 mg/m2/day by cont. IV infusion on days 1-5. Patients will receive dasatinib 100 mg QD on days 6-21. Consolidation therapy (4 cycles). Treatment consists of high-dose cytarabine 3 g/m2 (>60 years: 1 g/m2) q12h, days 1-3 iv over 3 hours. Patients will receive dasatinib 100 mg QD on days 4-21. Maintenance therapy: Patients completing consolidation therapy will continue to receive single agent dasatinib 100 mg QD for one year (or until relapse).

Geprüfte Regime

  • Dasatinib (Sprycel)
  • Cytarabine (ARA-cell)
  • Daunorubicin (Daunoblastin)
  • Idarubicin

Quelle: ClinicalTrials.gov


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