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A Phase 1 Study of LY5830966 in Participants With Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (PPV-MF), or Post-Essential Thrombocythemia Myelofibrosis (PET-MF) Who Have Been Failed by a Type I JAK2 Inhibitor (JAK2i)

RecruitingPhase 1

A Phase 1, Open-Label Study of LY5830966, a Type II JAK2 Inhibitor, in Patients With Myelofibrosis Previously Treated With a Type I JAK2 Inhibitor, JAK2 Inhibitor-Naïve Myelofibrosis, or High-risk Relapsed/Refractory Polycythemia Vera

Who can join

Ages 18 and older · All sexes

Full eligibility criteria
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%.

About the study

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.

What is being tested

Sponsor: Ajax Therapeutics, Inc., a wholly owned subsidiary of Eli Lilly and Company · Participants: 256 · Started: Oct 23, 2024

Contact the study team

Official record on ClinicalTrials.gov — NCT06343805

Locations in the U.S.

CaliforniaStanford Cancer Institute, Palo Alto
FloridaMoffitt Cancer Cancer Center, Tampa
KansasUniversity of Kansas Medical Center, Kansas City
MassachusettsDana Farber Cancer Institute, Boston
Massachusetts General Hospital, Boston
MichiganUniversity of Michigan, Ann Arbor
MissouriWashington University School of Medicine, St Louis
New YorkDavid H. Koch Center for Cancer Care at Memorial Sloan Kettering, New York
Icahn School of Medicine at Mount Sinai, New York
North CarolinaLevine Cancer Institute, Charlotte
OhioUniversity of Cincinnati, Cincinnati
The Ohio State University Comprehensive Cancer Center, Columbus
TexasMD Anderson Cancer Center, Houston

Conditions

From ClinicalTrials.gov, data retrieved Sep 30, 2026. Each study sets its own eligibility; the study team decides who can join.