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MethoTRExATE in MyelOpRolifErative Neoplasms (TREATMORE) Trial

Phase 2
Recruiting
Conditions
Myelofibrosis (MF)
Essential Thrombocythemia (ET)
Polycythemia Vera (PV)
Interventions
Registration Number
NCT06541249
Lead Sponsor
Icahn School of Medicine at Mount Sinai
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
54
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Myelofibrosis (MF)Methotrexate (MTX)18 patients with MF will be enrolled
Essential thrombocythemia (ET)Methotrexate (MTX)18 patients with MF will be enrolled
Polycythemia vera (PV)Methotrexate (MTX)18 patients with MF will be enrolled
Primary Outcome Measures
NameTimeMethod
MF Overall response rateat 24 weeks

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.

PV and ET Overall response rateat 24 weeks

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.

Secondary Outcome Measures
NameTimeMethod
Adverse event GradeUp to 48 Weeks

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.

Number of Participants with Myeloproliferative Neoplasm Symptom Assessment Form Score >50%Up to 48 Weeks

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).

Anemia Response RateUp to 48 Weeks

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).

Change in baseline hematocrit (PV cohort)Baseline and 48 Weeks

The change in the proportion of red blood cells in the blood measured using a hematocrit test. A hematocrit test measures the volume of packed red blood cells relative to whole blood. This is represented as a ratio. Change in baseline hematocrit will be measured for the PV cohort.

Spleen Response RateUp to 48 Weeks

Spleen response rate, defined as baseline splenomegaly palpable at 5-10cm becomes not palpable, or baseline splenomegaly of \>10cm decreases by \>50% by palpation.

Change in baseline platelet count (ET cohort)Baseline and 48 Weeks

A platelet count is a lab test that measures how many platelets are in the blood. Platelets are particles in the blood that help the blood clot. Platelets may be counted to monitor or diagnose diseases, or to look for the cause of too much bleeding or clotting. Change in baseline platelet count will be measured for ET cohort.

Change from baseline monthly phlebotomy rate (PV cohort)Baseline and 6 months

Change in number of therapeutic phlebotomy over a 6 month period prior to starting the clinical trial compared to when the patient completes the clinical trial.

Change from baseline platelet transfusion dependenceBaseline and 48 Weeks

Change in number of platelet transfusion over a 12 week period prior to starting the clinical trial compared to when the patient completes the clinical trial. (MF cohort)

Change from baseline pRBC transfusion dependenceat 24 and 48 Weeks

Change in number of pRBC transfusion over a 12 week period prior to starting the clinical trial compared to when the patient completes the clinical trial. (MF cohort)

Change from baseline in dosing of cytoreductive agents (PV and ET Cohort)Baseline and 48 Weeks

Change from baseline in dosing of cytoreductive agents other than Methotrexate for each patient.

Trial Locations

Locations (1)

Ruttenberg Treatment Center

🇺🇸

New York, New York, United States

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