Testing a new drug for patients with myelofibrosis who didn't respond to previous treatments

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This phase 1 clinical trial evaluates the safety and tolerability of AJ1-11095, a type II JAK2 inhibitor, in patients with primary myelofibrosis or secondary myelofibrosis who have previously failed treatment with a type I JAK2 inhibitor. The study employs a 3+3 dose escalation design followed by an expansion phase to determine the maximally tolerated dose and gather additional safety and efficacy data. Participants will be monitored for changes in biomarkers and clinical activity as part of the trial's objectives.

Why it matters

Who can join: the full rules

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%.

Where it's running

• Stanford Cancer Institute
  Palo Alto, California, United States Recruiting
• Moffitt Cancer Cancer Center
  Tampa, Florida, United States Recruiting
• University of Kansas Medical Center
  Kansas City, Kansas, United States Recruiting
• Massachusetts General Hospital
  Boston, Massachusetts, United States Recruiting
• Dana Farber Cancer Institute
  Boston, Massachusetts, United States Recruiting
• University of Michigan
  Ann Arbor, Michigan, United States Recruiting

Study contacts

• Principal investigator: John Mascarenhas, M.D. — Mt. Sinai
• Study coordinator: David Steensma, M.D.
• Email: david@ajaxtherapeutics.com
• Phone: 917-410-7250

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

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• Ruxolitinib given before, during, and after donor stem cell transplant for older adults with myelofibrosis or MDS/MPN overlap

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• National registry for people with myelofibrosis and anemia in Germany.

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• Comparing ASTX727 with and without Iadademstat for advanced blood cancers

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.