- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT02253277
Safety and Tolerability of Combined Treatment With Nilotinib and Ruxolitinib in CML and Ph+ ALL Patients (CoRNea)
A Phase Ib Single-arm, Open-label, Multicenter Study to Assess the Safety and Tolerability of Combined Treatment With Nilotinib 300mg BID and Ruxolitinib Increasing Dose in CML and Ph+ ALL Patients
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Type d'étude
Inscription (Réel)
Phase
- La phase 1
Contacts et emplacements
Lieux d'étude
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Berlin, Allemagne, 13353
- Novartis Investigative Site
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Frankfurt, Allemagne, 60590
- Novartis Investigative Site
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Jena, Allemagne, 07740
- Novartis Investigative Site
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Leipzig, Allemagne, 04103
- Novartis Investigative Site
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
Patients of the first stratum must have chronic myeloid leukemia receiving nilotinib first-line therapy or receiving second-line or subsequent-line treatment with nilotinib.
Patients of the second stratum must have CML in AP/BC or relapsed/refractory Ph+ ALL, or be Ph+ ALL patients with MRD with or without prior nilotinib pretreatment;
Patients must have adequate end organ function, as defined by:
- Creatinine < 2.0 x upper limit of normal (ULN)
- Total bilirubin < 1.5 x ULN (< 3.0 x ULN if related to disease or polymorphism, such as Mb. Gilbert)
- ALT and AST < 2.5 x ULN (< 5.0 x ULN if related to disease)
- Serum lipase ≤ 1.5 x ULN
- Alkaline phosphatase ≤ 2.5 x ULN (< 5.0 x ULN if related to disease);
Patients must have the following electrolyte values within normal limits or corrected to within normal limits with supplements prior to the first dose of study medication:
- Potassium
- Magnesium
- Phosphate
- Total calcium (corrected for serum albumin);
Female patients of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days before initiation of study drug. All WOCBP must use highly effective contraceptive methods throughout and during 3 months after study;
Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 for patients in CP, ≤ 2 for patients in AP/BC or with relapsed/refractory Ph+ ALL or with Ph+ ALL with MRD;
Patient has the following laboratory values within 7 days of starting study drug:
- For CML and Ph+ ALL patients: platelet count > 75 x 109/L and ANC > 1.0 x 109/L
Exclusion Criteria:
Patient must not have evidence of active malignancy other than the existing CML or ALL
Patient must not receive drugs that interfere with coagulation or inhibits platelet function, with the exception of aspirin ≤ 150 mg per day or low molecular weight heparin.
Patient must not have history of platelet dysfunction, bleeding diathesis, and/or coagulopathy in the 6 months prior to screening;
Patient must not require treatment with any strong CYP3A4 inducer or inhibitor
Patient must not have history of hypersensitivity to any of the study drugs or to drugs of similar chemical classes and their excipients;
Patients must not take other investigational drugs within 28 days prior to screening;
Patient must not be pregnant or lactating at screening and/or baseline;
Patient must not have impaired cardiac functions
Other protocol-defined inclusion/exclusion criteria may apply
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: N / A
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
---|---|
Expérimental: Nilotinib and Ruxolitinib
The study included two strata, which were to be treated in parallel.
The first stratum consisted of CML-patients in CP, which had been on nilotinib treatment before entering the study.
These patients did not optimally respond to the previous treatment.
The second stratum consisted of patients with CML in AP or BC and patients with relapsed/refractory Ph+ ALL and Ph+ ALL patients with MRD, with or without previous nilotinib treatment.
Patients were treated with 300mg nilotinib BID during the escalation phase (12 months) with increasing doses of ruxolitinib.
The dose expansion phase (12 months) began following the determination of the MTD of the combination and the decision to explore the cohort for confirmation of RPIID.
In this phase, safety and tolerability of the MTD and/or potential RPIID was to be further evaluated, with the purpose of establishing that this dose is suitable for use in this patient group.
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Nilotinib was supplied by Novartis as 150 mg and 200 mg hard gelatin capsules.
Nilotinib was not dosed by weight or body surface area.
Medication labels were in German and complied with the legal requirements of Germany.
They included storage conditions for the drug but no information about the patient.
The investigator emphasized compliance and instructed the patient to take nilotinib exactly as prescribed.
Ruxolitinib was supplied by Novartis as 5 mg, 15 mg, and 20 mg tablets.
Medication labels were in German and complied with the legal requirements of Germany.
They included storage conditions for the drug but no information about the patient.
The investigator emphasized compliance and instructed the patient to take ruxolitinib exactly as prescribed.
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Occurrence of dose limiting toxicities (DLTs)
Délai: Baseline, up to day 28 (equals first cycle)
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Occurrence of DLTs during cycle 1
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Baseline, up to day 28 (equals first cycle)
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Safety and tolerability profile of nilotinib and ruxolitinib administered in combination
Délai: Baseline, up to month 12
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Maximum Tolerated Dose (MTD) and/or Recommended Phase II Dose (RPIID) of ruxolitinib in combination with nilotinib.
(timeframe, baseline up to month 12)
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Baseline, up to month 12
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Trough levels of nilotinib and ruxolitinib administered in combination
Délai: Baseline, up to month 12
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Trough levels will be determined by measuring the minimum plasma concentration (Cmin).
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Baseline, up to month 12
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Clinical activity of nilotinib and ruxolitinib administered in combination
Délai: Baseline and at 3, 6, and 12 months
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Chronic myeloid leukemia in chronic phase: assessment of molecular response: MMR (≤0.1% BCR-ABL) and MR4 (≤0.001%
BCR-ABL) at 3, 6, 12 months; Advanced disease: assessment of cytogenetic response will be based on evaluating percentage of Ph+ metaphases
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Baseline and at 3, 6, and 12 months
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Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chercheur principal: Andreas Hochhaus, Prof. Dr. med., Universitätsklinikum Jena
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- CAMN107YDE19
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
Informations sur les médicaments et les dispositifs, documents d'étude
Étudie un produit pharmaceutique réglementé par la FDA américaine
Étudie un produit d'appareil réglementé par la FDA américaine
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .
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