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JOURNAL ONKOLOGIE – STUDIE

(PIONEER) Study to Evaluate Efficacy and Safety of Avapritinib (BLU-285), A Selective KIT Mutation-targeted Tyrosine Kinase Inhibitor, Versus Placebo in Patients With Indolent Systemic Mastocytosis

Rekrutierend

NCT-Nummer:
NCT03731260

Studienbeginn:
April 2019

Letztes Update:
21.07.2021

Wirkstoff:
Avapritinib, Placebo

Indikation (Clinical Trials):
Mastocytosis, Mastocytosis, Systemic

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
Blueprint Medicines Corporation

Collaborator:
-

Kontakt

Studienlocations
(3 von 38)

Leberkarzinomzentrum an der Uniklinik RWTH Aachen
Pauwelsstraße 30
52074 Aachen
(Nordrhein-Westfalen)
DeutschlandRekrutierend» Google-Maps
Charité Universitätsmedizin Berlin
10117 Berlin
(Berlin)
GermanyRekrutierend» Google-Maps
University Clinic Hamburg Eppendorf, University Cancer Center Hamburg (UCCH)
20246 Hamburg
(Hamburg)
GermanyRekrutierend» Google-Maps
Universitätsklinikum Schleswig-Holstein, Hämatologie/Onkologie
23538 Lübeck
(Schleswig-Holstein)
GermanyRekrutierend» Google-Maps
Universitätsklinik Mainz, Universitäts-Hautklinik, Clinical Research Center
55131 Mainz
(Rheinland-Pfalz)
GermanyRekrutierend» Google-Maps
Universitätsmedizin Mannheim, III. Medizinische Klinik
68167 Mannheim
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Klinikum rechts der Isar, Technische Universität München
80802 Munich
(Bayern)
GermanyRekrutierend» Google-Maps
University of Alabama at Birmingham
35294 Birmingham
United StatesRekrutierend» Google-Maps
Stanford Cancer Institute
94305 Stanford
United StatesRekrutierend» Google-Maps
Rush University Medical Center
60612 Chicago
United StatesRekrutierend» Google-Maps
University of Kansas Hospital
66160 Kansas City
United StatesRekrutierend» Google-Maps
Brigham & Women's Hospital
02115 Boston
United StatesRekrutierend» Google-Maps
Dana Farber Cancer Institute
02215 Boston
United StatesRekrutierend» Google-Maps
Michigan Medicine, University of Michigan
48106 Ann Arbor
United StatesRekrutierend» Google-Maps
Washington University School of Medicine
63110 Saint Louis
United StatesRekrutierend» Google-Maps
Herbert Irving Comprehensive Cancer Center
10032 New York
United StatesRekrutierend» Google-Maps
Duke University Health System (DUHS)
27710 Durham
United StatesRekrutierend» Google-Maps
Huntsman Cancer Institute
84112 Salt Lake City
United StatesRekrutierend» Google-Maps
Virginia Commonwealth University Medical Center
23298 Richmond
United StatesRekrutierend» Google-Maps
Odense Universitetshospital, ORCA/Allergicentret, Hudafdeling I og Allergicenter
DK-5000 Odense
DenmarkRekrutierend» Google-Maps
Hôpital de la Timone, Service de dermatologie
13385 Marseille
FranceRekrutierend» Google-Maps
Hôpital Pitié-Salpêtrière, Service de Dermatologie
75013 Paris
FranceRekrutierend» Google-Maps
CHU Toulouse Larrey, CEREMAST, Service de Dermatologie et Allergologie cutanée
31059 Toulouse
FranceRekrutierend» Google-Maps
A.O.U di Bologna - IRCCS, Istituto di Ematologia Lorenzo e Ariosto Seragnoli, Ematologia
40138 Bologna
ItalyRekrutierend» Google-Maps
Fondazione IRCCS Ca' Granda Ospedale Maggiore Poloclinico, UOC Ematologia
20122 Milan
ItalyRekrutierend» Google-Maps
A.O. OO.RR. S.Giovanni di Dio e Ruggi d'Aragona, University of Salerno
84131 Salerno
ItalyRekrutierend» Google-Maps
Azienda Ospedaliera Universitaria Integrata di Verona
37126 Verona
ItalyRekrutierend» Google-Maps
University Medical Center Groningen (UMCG)
9713 GZ Groningen
NetherlandsRekrutierend» Google-Maps
Erasmus Medical Center
3015 GD Rotterdam
NetherlandsRekrutierend» Google-Maps
Hospital Universitari Vall d'Hebron
08035 Barcelona
SpainRekrutierend» Google-Maps
lnstituto de Estudios de Mastocitosis de Castilla la Mancha, Hospital Virgen del Valle - Complejo Hospitalario de Toledo
45071 Toledo
SpainRekrutierend» Google-Maps
Karolinska University Hospital, Hematologimottagningen R51
141 86 Stockholm
SwedenRekrutierend» Google-Maps
NHS Greater Glasgow and Clyde, Beatson West of Scotland Cancer Centre
G12 OXL Glasgow
United KingdomRekrutierend» Google-Maps
Guy's and St Thomas' NHS Foundation Trust - Guy's Hospital
SE1 9RT London
United KingdomRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Brief Summary:

This is a Phase 2, randomized, double-blind, placebo-controlled study comparing the efficacy

and safety of avapritinib + best supportive care (BSC) with placebo + BSC in patients with

indolent systemic mastocytosis (ISM) whose symptoms are not adequately controlled by BSC. The

study will be conducted in 3 parts. All patients will receive treatment with avapritinib

during Part 3 including those rolling over from the placebo group.

Ein-/Ausschlusskriterien

Key Inclusion Criteria:

- 1. Patient must have SM, confirmed by Central Pathology Review of BM biopsy, and

central review of B- and C-findings by WHO diagnostic criteria.

- 2. Patient must have moderate-to-severe symptoms based on minimum mean total symptom

score (TSS) of the ISM Symptom Assessment Form (ISM-SAF) over the 14-day eligibility

screening period.

- 3. Patient must have failed to achieve adequate symptom control for 1 or more Baseline

symptoms.

- 4. For patients receiving corticosteroids, the dose must be ≤ 20 mg/d prednisone or

equivalent, and the dose must be stable for ≥ 14 days.

- 5. Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status

(PS) of 0 to 2.

Key Exclusion Criteria:

- 1. Patient has been diagnosed with any of the following WHO SM subclassifications:

cutaneous mastocytosis only, smoldering SM, SM with associated hematologic neoplasm,

aggressive SM, mast cell leukemia, or mast cell sarcoma.

- 2. Patient must not have received prior treatment with avapritinib.

- 3. Patient must not have had any cytoreductive therapy including but not limited to

masitinib and midostaurin, or investigational agent for < 14 days or 5 half-lives of

the drug (whichever is longer), and for cladribine, interferon alpha, pegylated

interferon, or antibody therapy < 28 days or 5 half-lives of the drug (whichever is

longer), before beginning the 14-day ISM-SAF eligibility TSS assessment.

- 4. Patient must not have received radiotherapy or psoralen and ultraviolet A (PUVA)

therapy < 14 days before beginning the 14-day ISM-SAF eligibility TSS assessment.

- 5. Patient must not have received any hematopoietic growth factor the preceding 14

days before beginning the 14-day ISM-SAF eligibility TSS assessment.

- 6. Patient must not have a QT interval corrected using Fridericia's formula (QTcF) of

> 480 msec.

Studien-Rationale

Primary outcome:

1. Part 1: Recommended Phase 2 dose (RP2D) in patients with ISM (Time Frame - 9 months)

2. Part 2: Proportion of responders, defined as ≥30% reduction in ISM Symptom Assessment Form (ISM-SAF) total symptom score (TSS) (Time Frame - 6 months):
0 - 120 points (higher value represents worse symptom outcomes)

Secondary outcome:

1. Part 2: Proportion of patients with a ≥50% reduction in serum tryptase (Time Frame - 6 months)

2. Part 2: Proportion of patients with a ≥50% reduction in peripheral blood V-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog aspartate 816 valine (KIT D816V) allele fraction or undetectable for patients with detectable mutation at Baseline (Time Frame - 6 months)

3. Part 2: Mean change in ISM Symptom Assessment Form (ISM-SAF) total symptom score (TSS) (Time Frame - 6 months)

4. Part 2: Proportion of patients with a ≥50% reduction in bone marrow mast cells or no aggregates for patients with aggregates at Baseline (Time Frame - 6 months)

5. Change in serum tryptase (Time Frame - Up to 5 years)

6. Change in V-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog aspartate 816 valine (KIT D816V) allele burden in blood (Time Frame - Up to 5 years)

7. Change in bone marrow mast cells (Time Frame - Up to 1 year after the end of Part 1 and Part 2)

8. Change in best supportive care (BSC) concomitant medication usage (Time Frame - Up to 5 years)

9. Change in Mastocytosis Quality of Life Questionnaire (MC-QoL) (Time Frame - Each study visit through Part 3 Cycle 12 (28-day cycles)):
0 - 100 points (higher value represents worse symptom outcomes)

10. Change in Patient's Global Impression of Symptom Severity (PGIS) (Time Frame - Each study visit through Part 3 Cycle 12 (28-day cycles)):
0 - 10 points (higher value represents worse symptom outcomes)

11. Change in 12-item Short Form Health Survey (SF-12) (Time Frame - Each study visit through Part 3 Cycle 12 (28-day cycles)):
0 - 100 points (higher value represents better symptom outcomes)

12. Change in Patients' Global Impression of Change (PGIC) (Time Frame - Each study visit through Part 3 Cycle 12 (28-day cycles)):
1 - 7 (higher value represents worse symptom outcomes)

13. Change in EuroQuol 5 Dimensions 5 Levels (EQ 5D-5L) (Time Frame - Each study visit through Part 3 Cycle 12 (28-day cycles)):
0 - 100 (higher value represents better symptom outcomes)

14. Safety of avapritinib as assessed by number of adverse events (Time Frame - Up to 5 years):
CTCAE version 5.0

15. Part 1 and Part 2 only: Area Under Curve (0 to Tau) for avapritinib (Time Frame - Every cycle (28 days) up to Cycle 4 (Part 1) and Cycle 7 (Part 2)):
h•ng/mL

Studien-Arme

  • Experimental: (Part 1) Avapritinib Dose 1 + BSC
    Avapritinib will be administered orally in continuous 28-day cycles
  • Experimental: (Part 1) Avapritinib Dose 2 + BSC
    Avapritinib will be administered orally in continuous 28-day cycles
  • Experimental: (Part 1) Avapritinib Dose 3 + BSC
    Avapritinib will be administered orally in continuous 28-day cycles
  • Placebo Comparator: (Part 1) Placebo + BSC
    Placebo will be administered orally in continuous 28-day cycles
  • Experimental: (Part 2) Avapritinib RP2D + BSC
    Avapritinib will be administered orally in continuous 28-day cycles
  • Placebo Comparator: (Part 2) Placebo + BSC
    Placebo will be administered orally in continuous 28-day cycles
  • Experimental: (Part 3) Avapritinib RP2D + BSC
    Avapritinib will be administered orally in continuous 28-day cycles

Geprüfte Regime

  • Avapritinib (BLU-285):
    Avapritinib tablet
  • Placebo:
    Placebo tablet

Quelle: ClinicalTrials.gov


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