Een fase 1-onderzoek naar AJ1-11095 bij patiënten met primaire myelofibrose (PMF), post-polycythaemia vera myelofibrose (PPV-MF) of post-essentiële trombocytemie myelofibrose (PET-MF) bij wie een type I JAK2-remmer niet werkt ( JAK2i)
Een multicenter, open-label, fase 1-onderzoek naar AJ1-11095 toegediend als orale monotherapie bij patiënten met primaire myelofibrose (PMF), post-polycythaemia vera myelofibrose (PPV-MF) of post-essentiële trombocytemie myelofibrose (PET-MF) Wie Zijn mislukt door een Type I JAK2-remmer (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.
Studie Overzicht
Gedetailleerde beschrijving
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.
Studietype
Inschrijving (Geschat)
Fase
- Fase 1
Contacten en locaties
Studiecontact
- Naam: Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or
- Telefoonnummer: 1-317-615-4559
- E-mail: LillyTrials@Lilly.com
Studie Contact Back-up
- Naam: Physicians interested in becoming principal investigators please contact
- E-mail: clinical_inquiry_hub@lilly.com
Studie Locaties
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Paris, Frankrijk
- Werving
- AP-HP Hopital Saint-Louis
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Contact:
- Jean-Jacques Kiladjian
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Italy
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Bologna, Italy, Italië
- Nog niet aan het werven
- IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant Orsola
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Contact:
- Francesca Palandri, MD
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Milan, Italy, Italië
- Nog niet aan het werven
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
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Contact:
- Francesco Passamonti, MD
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Barcelona, Spanje
- Werving
- Hospital Clinic Barcelona
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Contact:
- Ana Moreno Triguero
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Madrid, Spanje
- Werving
- Hospital Universitario Ramon y Cajal
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Contact:
- Valentin Garcia-Gutierrez
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Spain
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Madrid, Spain, Spanje
- Werving
- Hospital General Universitario Gregorio Maranon
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Contact:
- Santiago Osorio-Prendes, MD
- Telefoonnummer: 0034915868443
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UK
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London, UK, Verenigd Koninkrijk
- Nog niet aan het werven
- Guy's Hospital
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Contact:
- Claire Harrison, MD
- Telefoonnummer: 07939059512
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Oxford, UK, Verenigd Koninkrijk
- Nog niet aan het werven
- 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, Verenigde Staten, 94304
- Werving
- Stanford Cancer Institute
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Contact:
- William Shomali, MD
- Telefoonnummer: 650-498-6000
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Florida
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Tampa, Florida, Verenigde Staten, 33612
- Werving
- Moffitt Cancer Cancer Center
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Contact:
- Andrew Kuykendall, MD
- Telefoonnummer: 813-745-4639
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Kansas
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Kansas City, Kansas, Verenigde Staten, 66160
- Werving
- University of Kansas Medical Center
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Contact:
- Abdulraheem Yacoub, MD
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Massachusetts
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Boston, Massachusetts, Verenigde Staten, 02114
- Werving
- Massachusetts General Hospital
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Contact:
- Gabriela Hobbs, MD
- Telefoonnummer: 617-724-1124
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Boston, Massachusetts, Verenigde Staten, 02115
- Werving
- Dana Farber Cancer Institute
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Contact:
- Jacqueline Garcia, MD
- Telefoonnummer: 617-632-1906
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Michigan
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Ann Arbor, Michigan, Verenigde Staten, 48109
- Werving
- University of Michigan
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Contact:
- Kristen Pettit, MD
- Telefoonnummer: 734-647-2829
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Missouri
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St Louis, Missouri, Verenigde Staten, 63110
- Werving
- Washington University School of Medicine
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Contact:
- Stephen Oh, MD
- Telefoonnummer: 314-362-8814
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New York
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New York, New York, Verenigde Staten, 10029
- Werving
- Icahn School of Medicine at Mount Sinai
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Contact:
- John Mascarenhas, MD
- Telefoonnummer: 212-241-8839
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New York, New York, Verenigde Staten, 10021
- Werving
- 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, Verenigde Staten, 28204
- Werving
- Levine Cancer Institute
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Contact:
- Michael Grunwald, MD
- Telefoonnummer: 980-442-4363
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Ohio
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Cincinnati, Ohio, Verenigde Staten, 45221
- Werving
- University of Cincinnati
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Contact:
- Eric Vick, MD
- Telefoonnummer: 513-213-3203
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Columbus, Ohio, Verenigde Staten, 43210
- Werving
- The Ohio State University Comprehensive Cancer Center
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Contact:
- Uma Borate, MD
- Telefoonnummer: 614-685-9828
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Texas
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Houston, Texas, Verenigde Staten, 77030
- Werving
- MD Anderson Cancer Center
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Contact:
- Prithviraj Bose, MD
- Telefoonnummer: 713-792-7747
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
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%.
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Niet-gerandomiseerd
- Interventioneel model: Sequentiële toewijzing
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
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Experimenteel: Cohort 1
Dose A of LY5830966 taken orally by participants. |
Type II JAK2 Inhibitor
Andere namen:
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Experimenteel: Cohort 2
Dose B of LY5830966 taken orally by participants. |
Type II JAK2 Inhibitor
Andere namen:
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Experimenteel: Cohort 3
Dose C of LY5830966 taken orally by participants. |
Type II JAK2 Inhibitor
Andere namen:
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Experimenteel: Cohort 4
Dose D of LY5830966 taken orally by participants. |
Type II JAK2 Inhibitor
Andere namen:
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Experimenteel: Cohort 5
Dose E of LY5830966 taken orally by participants. |
Type II JAK2 Inhibitor
Andere namen:
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Experimenteel: Dose Expansion Cohort 1
Candidate RP3D of LY5830966 taken orally by participants. |
Type II JAK2 Inhibitor
Andere namen:
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Experimenteel: Dose Expansion Cohort 2
Alternative candidate RP3D of LY5830966 taken orally by participants. |
Type II JAK2 Inhibitor
Andere namen:
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Experimenteel: Dose Exploration Cohort 1
Dose F of LY5830966 taken orally by participants |
Type II JAK2 Inhibitor
Andere namen:
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Experimenteel: Dose Exploration Cohort 2
Dose G of LY5830966 taken orally by participants |
Type II JAK2 Inhibitor
Andere namen:
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Experimenteel: Dose Exploration Cohort 3
Dose H of LY5830966 taken orally by participants[ |
Type II JAK2 Inhibitor
Andere namen:
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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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).
Tijdsspanne: 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)
Tijdsspanne: 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
Tijdsspanne: 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
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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To assess clinical response to LY5830966 evaluated by the Total Symptom Score (TSS).
Tijdsspanne: 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.
Tijdsspanne: 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.
Tijdsspanne: 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.
Tijdsspanne: 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
Tijdsspanne: 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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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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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 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).
|
Medewerkers en onderzoekers
Onderzoekers
- Studie directeur: 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
Studie record data
Bestudeer belangrijke data
Studie start (Werkelijk)
Primaire voltooiing (Geschat)
Studie voltooiing (Geschat)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Werkelijk)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- 27978
- AJX-101 (Andere identificatie: Ajax Therapeutics, Inc.)
- 2025-522033-64-00 (Ctis)
- J8G-MC-JDIA (Andere identificatie: Eli Lilly and Company)
- 2025 (Subsidie/contract van de Amerikaanse NIH)
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
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