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JOURNAL ONKOLOGIE – STUDIE

A Phase 2 Study of CPI-0610 With and Without Ruxolitinib in Patients With Myelofibrosis

Rekrutierend

NCT-Nummer:
NCT02158858

Studienbeginn:
Juni 2014

Letztes Update:
29.01.2021

Wirkstoff:
CPI-0610, Ruxolitinib

Indikation (Clinical Trials):
Preleukemia, Leukemia, Myeloid, Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Primary Myelofibrosis, Myeloproliferative Disorders, Myelodysplastic-Myeloproliferative Diseases

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
Constellation Pharmaceuticals

Collaborator:
The Leukemia and Lymphoma Society

Studienleiter

Debbie Johnson
Study Director
Constellation Pharmaceuticals

Kontakt

Studienlocations
(3 von 56)

Universitätsklinikum Jena, Innere Medizin II
07747 Jena
(Thüringen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Gitta Bienert
Phone: (49 3641) 932-4673
E-Mail: Gitta.Bienert@med.uni-jena.de
» Ansprechpartner anzeigen
Universitätsklinikum Leipzig AöR
04103 Leipzig
(Sachsen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Karolin Hubert
Phone: (49 341) 971-3050
E-Mail: Karolin.Hubert@medizin.uni-leipzig.de
» Ansprechpartner anzeigen
Northwestern University - Lurie Comprehensive Cancer Center
60611 Chicago
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Pyone Maung
Phone: 312-926-4828
E-Mail: pyone.maung@northwestern.edu
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Washington University School of Medicne Neuromuscular Division Department of neurology
63110 Saint Louis
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Nicole Gaudin
Phone: 314-747-7960
E-Mail: nrgaudin@wustl.edu

Karyn Gordon
Phone: 314-362-0156
E-Mail: kdgordon@wustl.edu
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CHRU de Lille - Hopital Claude Huriez - Maladies du Sang
59000 Lille
FranceRekrutierend» Google-Maps
Ansprechpartner:
Florence Roge
Phone: (33 3) 2044-4290
E-Mail: florence.roge@chru-lille.fr
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Institut de cancérologie du Gard - Hematologie clinique
30029 Nîmes
FranceRekrutierend» Google-Maps
Ansprechpartner:
Maria Alessandra Damiano
Phone: (33 4) 6668-3528
E-Mail: MariaAlessandra.DAMIANO@chu-nimes.fr
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AOU S.Martino, IRCCS, IST-Istituto Nazionale Ricerca Sul Can
16132 Genova
ItalyRekrutierend» Google-Maps
Ansprechpartner:
Maria Grazia Ciardo
Phone: (39 010) 555-3302
E-Mail: Ciardomg.82@gmail.com
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IRCCS Policlinico San Matteo, Università degli studi di Pavi
16132 Genova
ItalyRekrutierend» Google-Maps
Ansprechpartner:
Adriana Carolei
Phone: (39 0382) 502-767
E-Mail: a.carolei@smatteo.pv.it
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Ospedale Maggiore Policlinico, Fondazione IRCCS Ca' Granda
20122 Milano
ItalyRekrutierend» Google-Maps
Ansprechpartner:
Silvia Artuso
Phone: (39 02) 5503-5420
E-Mail: silvia.artuso@policlinico.mi.it
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Servizio Sanitario Regionale Emilia-Romagna - Azienda Unita Sanitaria Locale (AUSL) di Rimini - Ospedale Infermi di Rimini
47923 Rimini
ItalyRekrutierend» Google-Maps
Ansprechpartner:
Dora Prota
Phone: (39 0541) 705-866
E-Mail: Dora.prota@auslromagna.it
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Ospedale di Circolo, PO Varese, AO Ospedale di Circolo e Fon
21100 Varese
ItalyRekrutierend» Google-Maps
Ansprechpartner:
Alessia Ingrassia
Phone: (39 033) 239-3904
E-Mail: alessia.ingrassia@asst-settelaghi.it
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Universiteit Maastricht Academisch Ziekenhuis Maastricht
6229 HX Maastricht
NetherlandsRekrutierend» Google-Maps
Ansprechpartner:
Claudia Geesing
Phone: (31 43) 388-2901
E-Mail: research.hematologie@mumc.nl
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Erasmus Universitair Medisch Centrum Rotterdam
3015 AA Rotterdam
NetherlandsRekrutierend» Google-Maps
Ansprechpartner:
Selina van Zelst
Phone: (31 10) 704-0704
E-Mail: s.vanzelst@erasmusmc.nl
» Ansprechpartner anzeigen
University College London Hospital's NHS foundation Trust
NW1 2BU London
United KingdomRekrutierend» Google-Maps
Ansprechpartner:
Faustine Laval
Phone: (44 203) 447-7240
E-Mail: faustine.laval@nhs.net
» Ansprechpartner anzeigen
Alle anzeigen

Studien-Informationen

Brief Summary:

Phase 1 Part (Complete): Open-label, sequential dose escalation study of CPI-0610 in patients

with previously treated Acute Leukemia, Myelodysplastic Syndrome,

Myelodysplastic/Myeloproliferative Neoplasms, and Myelofibrosis.

Phase 2 Part: Open-label study of CPI-0610 with and without Ruxolitinib in patients with

Myelofibrosis.

CPI-0610 is a small molecule inhibitor of bromodomain and extra-terminal (BET) proteins.

Ein-/Ausschlusskriterien

Inclusion Criteria

- Adult (aged ≥ 18 years)

- Phase 2 part: Patients with confirmed diagnosis of MF who meet all of the following

criteria:

- Dynamic International Prognostic Scoring System (DIPSS) risk category of

intermediate-1 or higher.

- ANC ≥ 1 x 10^9/L without the assistance of granulocyte growth factors

- Peripheral blood blast count <10%

- ECOG performance status ≤ 2.

- Adequate hematological, renal, hepatic, and coagulation laboratory assessments

- Patients must give written informed consent to participate in this study before the

performance of any study-related procedure.

For Arm 1 and 2 the following criteria should be considered:

- Palpable spleen ≥ 5 cm that is below the costal margin on physical examination OR RBC

transfusion dependent (defined as an average of ≥2 units of RBC transfusions per month

over the 12 weeks prior to enrollment)

- At least 2 symptoms measurable (score ≥ 1) using the Myelofibrosis Symptom Assessment

Form Version 4.0 (MFSAF v4.0)

- Platelet count ≥ 75 x 10^9/L without the assistance of thrombopoietic factors or

transfusions for at least 14 days

- Monotherapy Arm (Arm 1): Previously treated with a JAK inhibitor and be intolerant,

resistant, refractory or lost response to the JAK inhibitor

- Combination Arm (Arm 2): Must have received single agent ruxolitinib and be on a

stable dose for a minimum 8 weeks

For Arm 3 (JAK inhibitors naïve) the following criteria should be considered:

- Platelet count ≥ 100 x 10^9/L without the assistance of thrombopoietic factors or

transfusions

- Palpable spleen ≥ 5 cm that is below the costal margin on physical examination

- At least 2 symptoms measurable (score ≥ 3) or a total score of ≥ 10 using the MFSAF

v4.0

- No prior treatment with JAKi allowed

Exclusion Criteria

- Current known active or chronic infection with human immunodeficiency virus (HIV),

Hepatitis B or Hepatitis C.

- Impaired cardiac function or clinically significant cardiac diseases

- Patients with Child-Pugh Class B or C

- Impairment of gastrointestinal (GI) function or GI disease that could significantly

alter the absorption of CPI-0610 and/or ruxolitinib, including any unresolved nausea,

vomiting, or diarrhea that is CTCAE grade >1

- Prior treatment with a BET inhibitor.

- Pregnant or lactating women

- Any other concurrent severe and/or uncontrolled concomitant medical condition that

could compromise participation in the study

- Patients unwilling or unable to comply with this study protocol.

Studien-Rationale

Primary outcome:

1. Phase 2 Part: Evaluate spleen response (Time Frame - By imaging after 24 weeks)

2. Phase 2 Part: Evaluate the RBC (Red Blood Cell) transfusion independence rate (Time Frame - Absence of RBC transfusion and no hemoglobin level below 8 g/dL in the prior 12 weeks)

Secondary outcome:

1. Phase 2 Part: Evaluate the duration of spleen response by imaging (Time Frame - By palpation and imaging after 24 weeks)

2. Phase 2 Part: Evaluate response category rate (Time Frame - Rate of response by IWG-MRT after 24 weeks)

3. Phase 2 Part: Evaluate the change in patient reported outcomes (Time Frame - Changes from baseline in the total symptom score (MFSAF v4.0) and PGIC after 24 weeks)

4. Phase 2 Part: Evaluate the rate of RBC transfusion and the RBC transfusion dependence rate (Time Frame - Average number of RBC units per subject-month)

5. Phase 2 Part: Pharmacokinetic parameters of CPI-0610 and ruxolitinib: AUC and Cmax (Time Frame - Assessed during cycle 1 (first 21 days on study))

Studien-Arme

  • Experimental: Arm 1: Prior JAKi (JAK inhibitor) Monotherapy Arm
    Cohort 1A: Open to patients with MF who are Transfusion Dependent (TD) and who have previously been treated with a JAKi and are intolerant, resistant, refractory or lost response to the JAKi, or are ineligible to be treated with a JAKi.(CPI-0610 alone) Cohort 1B: Open to patients with MF who are not TD and who have previously been treated with a JAKi and are intolerant, resistant, refractory or lost response to the JAKi, or are ineligible to be treated with a JAKi. (CPI-0610 alone)
  • Experimental: Arm 2: Prior JAKi Combination Arm
    Cohort 2A: Open to patients with MF who are Transfusion Dependent (TD) and are currently taking ruxolitinib but have disease that is not being adequately controlled by ruxolitinib. (CPI-0610 + Ruxolitinib) Cohort 2B: Open to patients with MF who are not TD and are currently taking ruxolitinib but have disease that is not being adequately controlled by ruxolitinib. (CPI-0610 + Ruxolitinib)
  • Experimental: Arm 3: JAKi Naïve Combination Arm
    • Open to patients with MF who are anemic (i.e., Hemoglobin (Hgb) <10g/dL) and who have not previously received a JAKi. (CPI-0610 + Ruxolitinib)

Geprüfte Regime

  • CPI-0610
  • Ruxolitinib

Quelle: ClinicalTrials.gov


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