MethoTRExATE in MyelOpRolifErative Neoplasms (TREATMORE) Trial
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorIcahn School of Medicine at Mount Sinai
About this trial
Low-dose MTX is a widely used, inexpensive, and safe therapy used for decades and is well tolerated by patients with rheumatologic diseases. Recently, it was identified as a type 2 JAK inhibitor. If MTX proves to be safe and tolerable with a signal of clinical activity, this could have a significant benefit to patients with MPNs. Beyond the potential benefit of adding a type 2 JAK inhibitor to current therapy, this could signal the need to study MTX in MPNs further as a monotherapy. Discovering MTX as safe and clinically effective in MPNs could be profound on both a public health and global health scale for patients who are uninsured and cannot afford more expensive novel JAK inhibitors, or for those in countries where JAK inhibitors are not available. Accordingly, the research team deems it reasonable and prudent to assess the safety and efficacy of MTX in addition to current therapy for patients with MPN. The research team will evaluate patients for spleen responses, symptom responses, and cytologic responses. Correlative data will evaluate pharmacokinetic and disease modifying activity of MTX in MPNs to inform future clinical trials.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Be ≥18 years of age at time of signing the informed consent form (ICF)
Must voluntarily sign ICF and be willing and able to adhere to the study visit schedule and all protocol requirements
Have a pathologically confirmed diagnosis of PV, ET, PMF, post-ET-MF, or post-PV-MF as per WHO diagnostic criteria
Participants with MF may have low, intermediate 1, intermediate 2, or high-risk disease by Dynamic International Prognostic Scoring System (DIPSS). Participants with PV and ET with both low- and high-risk disease may be included.
Disqualifiers
Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
Prescribed MTX for another indication
History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months
Have other invasive malignancies within the last 3 years, except non-melanoma skin cancer and localized, cured prostate and cervical cancer
Trial design
Design model
Sequential
Treatments tested in this trial
Methotrexate (MTX)
DrugMTX has recently been identified as a dose-dependent JAK/STAT pathway inhibitor. 15mg will be given once a week orally.
Treatment groups
54 Participants
are divided into 3 treatment groupsGroup A: Myelofibrosis (MF)Experimental treatment 1 intervention
Group B: Polycythemia vera (PV)Experimental treatment 1 intervention
Group C: Essential thrombocythemia (ET)Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
MF Overall response rate
MF overall response rate, defined as Clinical Improvement (CI) or greater per the IWG-MRT and ELN Response Criteria for MF (2013). CI or greater is defined as changes in the spleen, hemoglobin, and symptoms.
Time frame
at 24 weeks2
PV and ET Overall response rate
PV overall response rate, defined as complete response (CR) or partial response (PR) by modified 2013 ELN criteria. CR response is defined as a lasting reduction in spleen size, symptom improvement, a reduction in platelet and white cell count. As well as changes in bone marrow biopsy. PR response is defined as lasting reduction in spleen size, symptom improvement, a reduction in platelet and white cell count.
Time frame
at 24 weeksSecondary outcomes
1
Adverse event Grade
The safety and the tolerability of treatment will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. This standardized system grades adverse events on a scale from 1 (mild) to 5 (death). Higher grades indicate more severe adverse events, with lower grades and fewer events suggesting better safety of the treatment.
Time frame
Up to 48 Weeks2
Number of Participants with Myeloproliferative Neoplasm Symptom Assessment Form Score >50%
Symptom improvement response is defined as a number of participants with improvement in symptoms response as defined by Myeloproliferative Neoplasms Symptoms Assessment Form (MPN-SAF). The MPN-SAF is a questionnaire that measures certain symptoms and how they improve throughout the study, from baseline. The questionnaire is divided into 4 sections - 1: 16 questions about the most common symptoms in these disease types, rated from 0 (lowest impact) to 10 (biggest impact); 2: Highest grade of fever; 3: Unintentional weight loss; 4. Quality of life, rated from 0 (as good as it can be) to 10 (as bad as it can be).
Time frame
Up to 48 Weeks3
Spleen Response Rate
Spleen response rate, defined as baseline splenomegaly palpable at 5-10cm becomes not palpable, or baseline splenomegaly of \>10cm decreases by \>50% by palpation.
Time frame
Up to 48 Weeks4
Anemia Response Rate
Anemia response rate will be measured as clinical improvement if patient hemoglobin increase by 2g/dl from baseline and/or become transfusion independent, according to International Working Group for Myelofibrosis Research and Treatment IWG-MRT criteria (MF cohort).
Time frame
Up to 48 WeeksSponsors and contacts
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Source ClinicalTrials.gov