Une étude de phase 1 sur l'AJ1-11095 chez des patients atteints de myélofibrose primitive (PMF), de myélofibrose post-polyglobulie vraie (PPV-MF) ou de myélofibrose post-thrombocytémie essentielle (PET-MF) qui ont échoué avec un inhibiteur JAK2 de type I ( JAK2i)
Une étude multicentrique ouverte de phase 1 sur l'AJ1-11095 administré en monothérapie orale chez des patients atteints de myélofibrose primitive (PMF), de myélofibrose post-polyglobulie vraie (PPV-MF) ou de myélofibrose thrombocytémique post-essentielle (PET-MF) qui ont échoué à cause d'un inhibiteur JAK2 de type I (JAK2i)
J8G-MC-JDIA (AJX-101) is a first-in-human (FIH), phase 1, non-randomized, multi-center, open-label clinical trial designed to investigate the safety, tolerability, pharmacokinetics (PK), clinical activity and changes in biomarkers of an orally administered type II Janus Kinase 2 (JAK2) inhibitor, LY5830966, in participants with primary or secondary myelofibrosis previously treated with at least one type I JAK2 inhibitor.
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
This is a phase 1, non-randomized, open-label study utilizing a 3+3 sequential dose escalation design followed by an expansion phase. The primary objective will be to evaluate the safety and tolerability of LY5830966 and establish a Maximally Tolerated Dose (MTD) and/or inform the establishment of a candidate Recommended Phase 3 dose (RP3D). The RP3D may be the maximally tolerated dose (MTD) or may be a dose below the MTD. The candidate RP3D will be based on adverse event (AE) pattern, pharmacokinetics (PK) and biomarker information, in addition to all available safety and efficacy data. Expansion cohorts will be enrolled to gather additional safety and efficacy information and to further refine input for future RP3D discussions. Eligible participants will have PMF, PPV-MF or PET-MF and will have either have relapsed after a response, or be refractory to, at least one prior type I JAK2 inhibitor therapy, either administered as monotherapy or in combination with another drug.
Type d'étude
Inscription (Estimé)
Phase
- La phase 1
Contacts et emplacements
Coordonnées de l'étude
- Nom: Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or
- Numéro de téléphone: 1-317-615-4559
- E-mail: LillyTrials@Lilly.com
Sauvegarde des contacts de l'étude
- Nom: Physicians interested in becoming principal investigators please contact
- E-mail: clinical_inquiry_hub@lilly.com
Lieux d'étude
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Barcelona, Espagne
- Recrutement
- Hospital Clinic Barcelona
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Contact:
- Ana Moreno Triguero
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Madrid, Espagne
- Recrutement
- Hospital Universitario Ramon y Cajal
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Contact:
- Valentin Garcia-Gutierrez
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Spain
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Madrid, Spain, Espagne
- Recrutement
- Hospital General Universitario Gregorio Maranon
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Contact:
- Santiago Osorio-Prendes, MD
- Numéro de téléphone: 0034915868443
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Paris, France
- Recrutement
- AP-HP Hopital Saint-Louis
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Contact:
- Jean-Jacques Kiladjian
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Italy
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Bologna, Italy, Italie
- Pas encore de recrutement
- IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant Orsola
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Contact:
- Francesca Palandri, MD
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Milan, Italy, Italie
- Pas encore de recrutement
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
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Contact:
- Francesco Passamonti, MD
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UK
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London, UK, Royaume-Uni
- Pas encore de recrutement
- Guy's Hospital
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Contact:
- Claire Harrison, MD
- Numéro de téléphone: 07939059512
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Oxford, UK, Royaume-Uni
- Pas encore de recrutement
- Genesis Cancer Care UK Limited - Oxford
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Contact:
- Adam Mead, MD
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California
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Palo Alto, California, États-Unis, 94304
- Recrutement
- Stanford Cancer Institute
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Contact:
- William Shomali, MD
- Numéro de téléphone: 650-498-6000
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Florida
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Tampa, Florida, États-Unis, 33612
- Recrutement
- Moffitt Cancer Cancer Center
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Contact:
- Andrew Kuykendall, MD
- Numéro de téléphone: 813-745-4639
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Kansas
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Kansas City, Kansas, États-Unis, 66160
- Recrutement
- University of Kansas Medical Center
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Contact:
- Abdulraheem Yacoub, MD
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Massachusetts
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Boston, Massachusetts, États-Unis, 02114
- Recrutement
- Massachusetts General Hospital
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Contact:
- Gabriela Hobbs, MD
- Numéro de téléphone: 617-724-1124
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Boston, Massachusetts, États-Unis, 02115
- Recrutement
- Dana Farber Cancer Institute
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Contact:
- Jacqueline Garcia, MD
- Numéro de téléphone: 617-632-1906
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Michigan
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Ann Arbor, Michigan, États-Unis, 48109
- Recrutement
- University of Michigan
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Contact:
- Kristen Pettit, MD
- Numéro de téléphone: 734-647-2829
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Missouri
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St Louis, Missouri, États-Unis, 63110
- Recrutement
- Washington University School of Medicine
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Contact:
- Stephen Oh, MD
- Numéro de téléphone: 314-362-8814
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New York
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New York, New York, États-Unis, 10029
- Recrutement
- Icahn School of Medicine at Mount Sinai
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Contact:
- John Mascarenhas, MD
- Numéro de téléphone: 212-241-8839
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New York, New York, États-Unis, 10021
- Recrutement
- David H. Koch Center for Cancer Care at Memorial Sloan Kettering
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Contact:
- Raajit Rampal, MD
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North Carolina
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Charlotte, North Carolina, États-Unis, 28204
- Recrutement
- Levine Cancer Institute
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Contact:
- Michael Grunwald, MD
- Numéro de téléphone: 980-442-4363
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Ohio
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Cincinnati, Ohio, États-Unis, 45221
- Recrutement
- University of Cincinnati
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Contact:
- Eric Vick, MD
- Numéro de téléphone: 513-213-3203
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Columbus, Ohio, États-Unis, 43210
- Recrutement
- The Ohio State University Comprehensive Cancer Center
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Contact:
- Uma Borate, MD
- Numéro de téléphone: 614-685-9828
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Texas
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Houston, Texas, États-Unis, 77030
- Recrutement
- MD Anderson Cancer Center
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Contact:
- Prithviraj Bose, MD
- Numéro de téléphone: 713-792-7747
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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:
- Diagnosis of PMF, post-PV MF, or post-ET MF.
- Dynamic International Prognostic Scoring System (DIPSS) Intermediate-1, Intermediate-2 or High-risk MF with less than or equal to (≤)10% blasts, regardless of JAK2 mutation status.
- Estimated spleen volume greater than or equal to (≥)450 cubic centimeter (cm ³)
- Myelofibrosis Symptom Assessment Form, version 4.0 (MFSAF v.4.0) TSS ≥10, or at least 2 of 7 MFSAF-assessed symptoms with scores ≥3.
- Eastern Cooperative Oncology Group performance score (ECOG PS) of 0, 1, 2, or 3.
- Prior therapy with at least 1 type I JAK2 inhibitor, and either failed to achieve a response or relapsed after achieving a response.
- Absolute neutrophil count greater than or equal to 1,000 per microliter of blood (ANC ≥1.0×10^9/L).
- Platelet count ≥75×10^9/L.
- Estimated glomerular filtration rate greater than or equal to 45 milliliters per minute per 1.73 square meters (eGFR ≥45 mL/min/1.73m²).
- Serum total bilirubin ≤2.0 × upper limit of normal (ULN).
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 × upper limit normal (ULN).
- QTcF ≤470 msec.
Polycythemia vera (PV) Only
- Confirmed diagnosis of PV
- Participants must have high-risk disease as defined by 60 years of age or older and/or have prior history of thrombotic event
- R/R or intolerant to at least one line of prior therapy including but not limited to interferon-based therapies, ruxolitinib, or hydroxyurea (HU) as defined by European LeukemiaNet (ELN) criteria
Exclusion Criteria:
- Prior splenectomy or splenic irradiation within 3 months.
- Ongoing use of systemic corticosteroids at dose equivalent to greater than (>) 20 milligrams per day (mg/day) of prednisone.
- Active, uncontrolled systemic infection or active Hepatitis B or C
- Chemotherapy in the previous 4 weeks or prior JAK2 inhibitor not discontinued per required washout prior to first dose
- Peripheral neuropathy ≥ Grade 2 (NCI CTCAE v 5.0).
- Pregnant or breastfeeding: males planning to father a child during treatment and for 3 months after last dose.
- Requirement for therapy with a medication that is a strong Cytochrome P450 3A4 CYP3A4 inhibitor as a concomitant medication.
- Currently on an interventional therapeutic trial in the treatment phase.
- Significant cardiovascular disease
- Active second primary malignancy (or diagnosed within 2 years) at high risk of progression, with standard exceptions (treated skin cancer, in situ cervical cancer, curatively treated localized breast/prostate cancer)
- Prolongation of the corrected QTcF ≥470 millisecond during screening
- Individual with a history of (noninfectious) pneumonitis/interstitial lung disease.
First line (1L) MF only:
- Prior treatment with JAK2 inhibitors
High-risk R/R PV only:
- Prior PV-directed therapy without required washout
- Active or chronic bleeding within 2 months prior to enrollment
- Clinically significant thrombosis (e.g., pulmonary embolism, deep vein thrombosis, or splenic vein thrombosis) within 2 months prior to enrollment
- Requires phlebotomy at hematocrit levels <45%.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Non randomisé
- Modèle interventionnel: Affectation séquentielle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: Cohort 1
Dose A of LY5830966 taken orally by participants. |
Type II JAK2 Inhibitor
Autres noms:
|
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Expérimental: Cohort 2
Dose B of LY5830966 taken orally by participants. |
Type II JAK2 Inhibitor
Autres noms:
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Expérimental: Cohort 3
Dose C of LY5830966 taken orally by participants. |
Type II JAK2 Inhibitor
Autres noms:
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Expérimental: Cohort 4
Dose D of LY5830966 taken orally by participants. |
Type II JAK2 Inhibitor
Autres noms:
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Expérimental: Cohort 5
Dose E of LY5830966 taken orally by participants. |
Type II JAK2 Inhibitor
Autres noms:
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Expérimental: Dose Expansion Cohort 1
Candidate RP3D of LY5830966 taken orally by participants. |
Type II JAK2 Inhibitor
Autres noms:
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Expérimental: Dose Expansion Cohort 2
Alternative candidate RP3D of LY5830966 taken orally by participants. |
Type II JAK2 Inhibitor
Autres noms:
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Expérimental: Dose Exploration Cohort 1
Dose F of LY5830966 taken orally by participants |
Type II JAK2 Inhibitor
Autres noms:
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Expérimental: Dose Exploration Cohort 2
Dose G of LY5830966 taken orally by participants |
Type II JAK2 Inhibitor
Autres noms:
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Expérimental: Dose Exploration Cohort 3
Dose H of LY5830966 taken orally by participants[ |
Type II JAK2 Inhibitor
Autres noms:
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Number of patients with treatment-emergent adverse events (TEAEs) as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v 5.0).
Délai: Baseline through study completion, an average of 1 year
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Treatment Emergent AEs will be assessed during routine study visits and compared to Baseline to continuously evaluate safety and tolerability of LY5830966. |
Baseline through study completion, an average of 1 year
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Number of patients with Dose Limiting Toxicities (DLTs)
Délai: Baseline through study completion, an average of 1 year
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Protocol-defined potential DLTs will be assessed by the Safety Review Committee at routine intervals. |
Baseline through study completion, an average of 1 year
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To establish the maximum tolerated dose (MTD) and/or recommended phase 3 dose (RP3D) of LY5830966
Délai: Baseline through study completion, an average of 1 year
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Safety evaluations will occur consistently for each patient and across patients to assess MTD or RP3D. See description of safety evaluations described in outcomes 1 and 2 mentioned above. |
Baseline through study completion, an average of 1 year
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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To assess clinical response to LY5830966 evaluated by the Total Symptom Score (TSS).
Délai: Baseline through Week 24
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Number and proportion of patients with an improvement of ≥50% from Baseline in Total TSS as well as time to TSS response and duration of TSS response using the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0. The TSS is a 7 question assessment form with lower scores indicating better outcomes. |
Baseline through Week 24
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To assess clinical response to LY5830966 evaluated by spleen volume assessments.
Délai: Baseline through Week 24
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Spleen volume reduction (SVR) of ≥35% from Baseline measured by magnetic resonance imaging (MRI) or computed tomography (CT). |
Baseline through Week 24
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To assess clinical response to LY5830966 evaluated by spleen length assessments.
Délai: Baseline through Week 24
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Proportion of subjects with ≥50% reduction in length of spleen assessed by palpation. |
Baseline through Week 24
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To assess clinical response to LY5830966 evaluated through spleen size improvement.
Délai: Baseline through Week 24
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Time to spleen size improvement response measured by patient and across all patients. |
Baseline through Week 24
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To evaluate the Area Under the Curve (AUC) of LY5830966
Délai: Pre dose and post dose Cycle 1 (Day 1, and Day 2 (24hrs post), and Cycle 2 (Day 1 and 24 hrs post).
|
AUC time curve from 0 to 24 hrs post dose and percent difference between intervals will be evaluated. |
Pre dose and post dose Cycle 1 (Day 1, and Day 2 (24hrs post), and Cycle 2 (Day 1 and 24 hrs post).
|
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To evaluate the Cmax of LY5830966
Délai: Pre dose and post dose Cycle 1 (Day 1, and Day 2 (24hrs post), and Cycle 2 (Day 1 and 24 hrs post).
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The maximum observed plasma concentration will be evaluated. |
Pre dose and post dose Cycle 1 (Day 1, and Day 2 (24hrs post), and Cycle 2 (Day 1 and 24 hrs post).
|
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To evaluate the Tmax of LY5830966
Délai: Pre dose and post dose Cycle 1 (Day 1, and Day 2 (24hrs post), and Cycle 2 (Day 1 and 24 hrs post).
|
The duration of time taken to reach Cmax will be evaluated. |
Pre dose and post dose Cycle 1 (Day 1, and Day 2 (24hrs post), and Cycle 2 (Day 1 and 24 hrs post).
|
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To evaluate the half-life of LY5830966
Délai: Pre dose and post dose Cycle 1 (Day 1, and Day 2 (24hrs post), and Cycle 2 (Day 1 and 24 hrs post).
|
The depletion of AJ1-00195 in the body will be observed over time. |
Pre dose and post dose Cycle 1 (Day 1, and Day 2 (24hrs post), and Cycle 2 (Day 1 and 24 hrs post).
|
Collaborateurs et enquêteurs
Les enquêteurs
- Directeur d'études: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
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
- 27978
- AJX-101 (Autre identifiant: Ajax Therapeutics, Inc.)
- 2025-522033-64-00 (Ctis)
- J8G-MC-JDIA (Autre identifiant: Eli Lilly and Company)
- 2025 (Subvention/contrat des NIH des États-Unis)
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
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