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JOURNAL ONKOLOGIE – STUDIE

An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of KRT-232 Combined With Low-Dose Cytarabine (LDAC) or Decitabine in Patients With Acute Myeloid Leukemia (AML)

Rekrutierend

NCT-Nummer:
NCT04113616

Studienbeginn:
September 2019

Letztes Update:
07.12.2020

Wirkstoff:
KRT-232, Cytarabine, Decitabine

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

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
Kartos Therapeutics, Inc.

Collaborator:
-

Kontakt

Studienlocations
(3 von 25)

Hauttumorzentrum am Universitätsklinikum Halle
Ernst-Grube-Straße 40
06120 Halle (Saale)
(Sachsen-Anhalt)
DeutschlandRekrutierend» Google-Maps
Universitaetsklinikum Schleswig-Holstein
Lübeck
(Schleswig-Holstein)
GermanyRekrutierend» Google-Maps
Northwestern University
60611 Chicago
United StatesRekrutierend» Google-Maps
University of Maryland Medical Center
21201 Baltimore
United StatesRekrutierend» Google-Maps
Memorial Sloan Kettering Cancer Center
10065 New York
United StatesRekrutierend» Google-Maps
The Ohio State University
43210 Columbus
United StatesRekrutierend» Google-Maps
Oregon Health and Science University
97239 Portland
United StatesRekrutierend» Google-Maps
MD Anderson Cancer Center
77030 Houston
United StatesRekrutierend» Google-Maps
Centre Hospitalier Universitaire (CHU) de Bordeaux
33000 Bordeaux
FranceRekrutierend» Google-Maps
Centre Hospitalier Universitaire (CHU) de Nice
06000 Nice
FranceRekrutierend» Google-Maps
Hospital Universitari Vall d'Hebron
08035 Barcelona
SpainRekrutierend» Google-Maps
Hospital Universitario de Gran Canaria Doctor Negrin
35010 Las Palmas
SpainRekrutierend» Google-Maps
Hospital Universitario Ramon y Cajal
28034 Madrid
SpainRekrutierend» Google-Maps
Hospital Universitario Virgen de la Victoria de Málaga
29010 Málaga
SpainRekrutierend» Google-Maps
Hospital Universitario de Salamanca
37007 Salamanca
SpainRekrutierend» Google-Maps
Hospital Clínico Universitario de Valencia
46010 Valencia
SpainRekrutierend» Google-Maps
Cardiff University
CF10 3AT Cardiff
United KingdomRekrutierend» Google-Maps
The Royal Marsden Hospital
SW3 6JJ London
United KingdomRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Brief Summary:

This study evaluates KRT-232, a novel oral small molecule inhibitor of MDM2, combined with

low-dose cytarabine (LDAC) or Decitabine for the treatment of adults with Acute Myeloid

Leukemia (AML) and AML secondary to myeloproliferative neoplasms (MPN). Participants must be

relapsed/refractory (having failed prior therapy) and will be assigned to receive KRT+232

with LDAC or KRT-232 with Decitabine.

Ein-/Ausschlusskriterien

Key Inclusion Criteria:

- Part A: Patients with relapsed or refractory AML, or newly-diagnosed AML secondary to

MPN

- Part B: Patients with AML secondary to MPN or JAK2 mutation positive AML; patients may

have been treated with 0 to 2 prior lines of therapy for their AML

- Adequate hepatic and renal function

- Appropriate prior treatment with an FLT3 or IDH1/2 inhibitor where applicable

Key Exclusion Criteria:

- Patients who are TP53 mutation positive

- Prior treatment with an MDM2 antagonist therapy

- Patients treated with ≥ 18 g/m2 of cytarabine within the prior 90 days are not

eligible to be treated with cytarabine on this study (but may be treated with

decitabine)

- Patients previously treated with decitabine are not eligible to receive decitabine on

this study (but may be treated with cytarabine)

- Patients who have received an allogeneic HSCT within 90 days of enrollment or are

eligible for an allogeneic HSCT and have a donor (unless transplant is refused)

- Active graft-versus-host disease requiring active therapy or who have received

immunosuppressive therapy for graft-versus-host disease within 1 month prior

- Patients with known CNS involvement with AML, acute promyelocytic leukemia (APL), or a

history of bleeding diathesis

- Patients who have had major surgery within 28 days prior

- Women who are pregnant or breastfeeding

Studien-Rationale

Primary outcome:

1. Part A: Number of dose-limiting toxicities (DLTs) of KRT-232 in combination with cytarabine or decitabine (Time Frame - 28 Days)

2. Part B: Proportion of patients achieving complete remission (CR) or complete remission with partial hematological improvement (CRh) as determined by European LeukemiaNet (ELN) response criteria (Time Frame - 28 Days)

Secondary outcome:

1. Part A: Proportion of patients achieving complete remission (CR) or complete remission with partial hematological improvement (CRh) as determined by European LeukemiaNet (ELN) response criteria (Time Frame - 28 Days)

2. Proportion of patients achieving a morphologic leukemia-free state (MLFS), or complete remission with incomplete hematology recovery (CRi), or composite complete remission (CRc = CR + CRh), or partial remission (PR) (Time Frame - 28 Days)

Studien-Arme

  • Experimental: KRT-232+LDAC
    KRT-232 will be administered orally, once daily (QD), on Days 1-7 in combination with LDAC administered at 20 mg/m2/day subcutaneously on Days 1-10 in a 28-day cycle.
  • Experimental: KRT-232(7-Day)+Decitabine
    KRT-232 will be administered orally, once daily (QD), on Days 1-7 in combination with Decitabine administered at 20 mg/m2/day intravenously on Days 1-5 in a 28-day cycle.
  • Experimental: KRT-232(14-Day)+Decitabine
    KRT-232 will be administered orally, once daily (QD), on Days 1-7 and Days 15-21 (7 days on/7 days off/7 days on/7 days off) in combination with Decitabine administered at 20 mg/m2/day intravenously on Days 1-5 in a 28-day cycle.

Geprüfte Regime

  • KRT-232:
    KRT-232 is an experimental MDM2 inhibitor anti-cancer drug taken by mouth.
  • Cytarabine (cytosine arabinoside / Cytosar-U / Depocyt / Arabinosylcytosine / Ara-C / ):
    Cytarabine is an anti-cancer chemotherapy drug taken via injection.
  • Decitabine (Dacogen):
    Decitabine is an anti-cancer chemotherapy drug taken via injection.

Quelle: ClinicalTrials.gov


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