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JOURNAL ONKOLOGIE – STUDIE
A Study Evaluating Safety and Tolerability, and Pharmacokinetics of Navitoclax Monotherapy and in Combination With Ruxolitinib in Participants With Myeloproliferative Neoplasm
Rekrutierend
NCT-Nummer:
NCT04041050
Studienbeginn:
November 2019
Letztes Update:
06.07.2021
Wirkstoff:
Navitoclax, Ruxolitinib, Celecoxib
Indikation (Clinical Trials):
Neoplasms, Myeloproliferative Disorders
Geschlecht:
Alle
Altersgruppe:
Erwachsene (18+)
Phase:
Phase 1
Sponsor:
AbbVie
Collaborator:
-
Studienleiter
Study Director
AbbVie
Kontakt
Kontakt:
Phone: 844-663-3742
E-Mail: abbvieclinicaltrials@abbvie.com» Kontaktdaten anzeigen
Studienlocations
(3 von 24)
79106 Freiburg
(Baden-Württemberg)
GermanyNoch nicht rekrutierend» Google-Maps
13353 Berlin
(Berlin)
GermanyNoch nicht rekrutierend» Google-Maps
34125 Kassel
(Hessen)
GermanyNoch nicht rekrutierend» Google-Maps
18057 Rostock
(Mecklenburg-Vorpommern)
GermanyNoch nicht rekrutierend» Google-Maps
90095-1678 Los Angeles
United StatesNoch nicht rekrutierend» Google-Maps
60611-2927 Chicago
United StatesNoch nicht rekrutierend» Google-Maps
44718 Canton
United StatesNoch nicht rekrutierend» Google-Maps
23219 Richmond
United StatesNoch nicht rekrutierend» Google-Maps
1200 Woluwe-Saint-Lambert
BelgiumNoch nicht rekrutierend» Google-Maps
25123 Brescia
ItalyRekrutierend» Google-Maps
47014 Meldola
ItalyNoch nicht rekrutierend» Google-Maps
36100 Vicenza
ItalyNoch nicht rekrutierend» Google-Maps
247-8533 Kamakura-shi
JapanRekrutierend» Google-Maps
589-8511 Osakasayama-shi
JapanRekrutierend» Google-Maps
565-0871 Suita-shi
JapanRekrutierend» Google-Maps
113-8431 Bunkyo-ku
JapanRekrutierend» Google-Maps
409-3821 Chuo-shi
JapanRekrutierend» Google-Maps
08907 Hospitalet de Llobregat
SpainRekrutierend» Google-Maps
31008 Pamplona
SpainRekrutierend» Google-Maps
28027 Madrid
SpainRekrutierend» Google-Maps
40447 Taichung City
TaiwanRekrutierend» Google-Maps
80708 Kaohsiung
TaiwanRekrutierend» Google-Maps
SE1 9RT London
United KingdomNoch nicht rekrutierend» Google-Maps
OX3 7LE Oxford
United KingdomNoch nicht rekrutierend» Google-Maps
Studien-Informationen
Brief Summary:There are 4 parts to this study for which the primary objectives are to evaluate safety and
tolerability, including dose-limiting toxicities (DLTs), and pharmacokinetics (PK) of
navitoclax when administered alone (Part 1) or when administered in combination with
ruxolitinib (Part 2). In Part 2, participants must have been receiving a stable dose of
ruxolitinib therapy for at least 12 weeks prior to study enrollment. In Part 3, all eligible
participants will receive navitoclax, with the primary objective being to evaluate potential
navitoclax effect on QTc prolongation. In Part 4, effect of navitoclax is evaluated on the
PK, safety, and tolerability of a single dose of celecoxib in participants with
myeloproliferative neoplasm (MPN) or chronic myelomonocytic leukemia (CMML).
Ein-/Ausschlusskriterien
Inclusion Criteria:Parts 1 and 2:
- Navitoclax Monotherapy (Part 1 Only - Japanese Participants):
- Documented diagnosis of myelofibrosis (MF), polycythemia vera (PV) or essential
thrombocythemia (ET) as defined by the World Health Organization (WHO)
classification.
- MF participants must have received and failed or are intolerant to ruxolitinib
therapy.
- ET or PV participants must be requiring cytoreduction who have failed or are
intolerant to at least one prior therapy, or who refuse standard therapy.
- Navitoclax + ruxolitinib Combination Therapy (Part 2 Only - Japanese and Taiwanese
Participants):
- Has documented diagnosis of primary MF, post-polycythemia vera MF (PPV-MF), or
post-essential thrombocythemia (PET-MF) as defined by the World Health
Organization (WHO) classification.
- Is ineligible or unwilling to undergo stem cell transplantation at time of study
entry.
- Has splenomegaly as defined by a spleen palpable >= 5 cm below costal margin or
spleen volume >= 50 cm^3 as assessed by magnetic resonance imaging (MRI) or
computed topography (CT) scan.
- Must have received ruxolitinib therapy for at least 12 weeks and be currently on
a stable dose of ruxolitinib (as described in the protocol).
- Must have adequate bone marrow, kidney, liver and hematology blood values as detailed
in the study protocol.
- Part 1 only: Cytoreduction for participants with ET and PV therapy within 14 days
prior to the first dose of navitoclax will be allowed pending additional discussion
with study doctor. Ruxolitinib for MF participants will not be allowed within 7 days
prior to the first dose of study drug and during navitoclax administration.
- Eastern Cooperative Oncology Group (ECOG) performance status <= 1.
Part 3 and Part 4:
- Part 3 Only: At screening or baseline (pre-dose on Day 1), participant has QT interval
corrected for heart rate (QTc) interval by Fridericia's correction (QTcF) <= 470 msec.
- Participants with a documented diagnosis of primary or secondary MF, ET, PV or chronic
myelomonocytic leukemia (CMML) as defined by the WHO classification.
- Participants must be requiring treatment and have failed or are intolerant to at least
one prior therapy or who refuse standard therapy.
- ECOG performance status <= 2.
- Must have adequate bone marrow, kidney, liver and hematology blood values as detailed
in the study protocol.
Exclusion Criteria:
Part 1 and 2:
- Shows leukemic transformation (> 10% blasts in peripheral blood or bone marrow
biopsy).
- Has a history of an active malignancy other than MPN within the past 2 years prior to
study entry (exceptions detailed in the protocol).
- Has a positive test result for HIV at screening.
- Has chronic active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
requiring treatment.
- Has evidence of other clinically significant uncontrolled condition(s).
- Has previously taken a BH3 mimetic compound.
- Currently on medications that interfere with coagulation (including warfarin) or
platelet function with the exception of low dose aspirin (up to 100 mg) and
low-molecular-weight heparin (LMWH).
- Has received strong or moderate CYP3A inhibitors (e.g., ketoconazole, clarithromycin)
within 14 days prior to the administration of the first dose of navitoclax.
Part 3 and Part 4:
- Had prior therapy with a BH3 mimetic compound.
- Have received strong or moderate CYP3A inhibitors within 28 days or 5 half-lives of
the drug (whichever is shorter) prior to the first dose of navitoclax.
- Have received strong CYP3A inducers within 10 days prior to the first dose of
navitoclax.
- Show leukemic transformation (> 10% blasts in peripheral blood or bone marrow biopsy).
- Currently on medications that interfere with coagulation (including warfarin) or
platelet function except for low-dose aspirin (up to 100 mg) and LMWH.
Part 4 Only:
- Have received CYP2C9 inhibitors within 28 days or 5 half-lives of the drug (whichever
is shorter) prior to the first dose of study drugs.
- Have received CYP2C9 inducers within 10 days prior to the first dose of study drugs.
Studien-Rationale
Primary outcome:1. Number of Participants with Dose Limiting Toxicities (DLT) (Time Frame - Up to 28 days after the navitoclax initiation):
Dose limiting toxicities for dose escalation purposes will be determined on events that occur during the first 28-day cycle of navitoclax.
2. Maximum Observed Plasma Concentration (Cmax) of Navitoclax (Time Frame - Up to approximately 1 day):
Maximum Observed Plasma Concentration (Cmax) of Navitoclax.
3. Maximum Observed Plasma Concentration (Cmax) of Celecoxib (Part 4) (Time Frame - Up to approximately 1 day):
Maximum Observed Plasma Concentration (Cmax) of Celecoxib.
4. Time to Cmax (peak time, Tmax) of Navitoclax (Time Frame - Up to approximately 1 day):
Tmax defined as time to maximum observed plasma concentration of Navitoclax.
5. Time to Cmax (peak time, Tmax) of Celecoxib (Part 4) (Time Frame - Up to approximately 1 day):
Tmax defined as time to maximum observed plasma concentration of Celecoxib.
6. Area Under the Plasma Concentration-time Curve from time 0 to the time of the last measurable concentration (AUCt) of Navitoclax (Time Frame - Up to approximately 2 days):
Area under the plasma concentration-time curve from time zero to the last measurable concentration of Navitoclax.
7. Area Under the Plasma Concentration-time Curve from time 0 to the time of the last measurable concentration (AUCt) of Celecoxib (Part 4) (Time Frame - Up to approximately 2 days):
Area under the plasma concentration-time curve from time zero to the last measurable concentration of Celecoxib.
8. Number of Participants with Adverse Events (Time Frame - From first dose of study drug until 30 days following last dose of study drug (up to approximately 3 years).):
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
9. Change in QT interval corrected for heart rate interval by Fridericia's correction formula (QTcF) (Part 3) (Time Frame - From first dose of study drug until 30 days following last dose of study drug.):
Change in QTCF (Part 3).
Secondary outcome:
1. Overall Response Rate (ORR) (Time Frame - Up to approximately 96 weeks):
ORR is defined as the sum of rates of complete remission (CR) + partial remission (PR) associated with the addition of navitoclax to ruxolitinib according to the International Working Group-Myeloproliferative Neoplasms Research and Treatment/European Leukemia Net (IWG-MRT/ELN) criteria.
Studien-Arme
- Experimental: Part 1: Navitoclax Monotherapy
Participants will receive various doses of navitoclax once daily (QD). - Experimental: Part 2: Navitoclax + Ruxolitinib Combination Therapy
Participants will receive various doses of navitoclax once daily (QD) in combination with ruxolitinib twice daily (BID). - Experimental: Part 3: Navitoclax Monotherapy
Participants will receive navitoclax Dose A once daily (QD). - Experimental: Part 4: Navitoclax + Celecoxib
Participants will receive navitoclax dose A once daily (QD) from Day 3 through Day 16. Participants will also receive celecoxib singe dose on Day 1 and Day 7.
Geprüfte Regime
- Navitoclax (ABT-263):
Tablet; Oral - Ruxolitinib:
Tablet; Oral - Celecoxib (Celebrex):
Capsule; Oral
Quelle: ClinicalTrials.gov
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