MethoTRExATE in MyelOpRolifErative Neoplasms (TREATMORE) Trial

NCT06541249 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: STUDY-24-00071
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

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.

Conditions

Polycythemia Vera (PV); Essential Thrombocythemia (ET); Myelofibrosis (MF)

Outcome Measures

Primary Outcomes (2)

• 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.

  at 24 weeks

• 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.

  at 24 weeks

Secondary Outcomes (10)

• Adverse event Grade

  Up to 48 Weeks

• Number of Participants with Myeloproliferative Neoplasm Symptom Assessment Form Score >50%

  Up to 48 Weeks

• Spleen Response Rate

  Up to 48 Weeks

• Anemia Response Rate

  Up to 48 Weeks

• Change in baseline hematocrit (PV cohort)

  Baseline and 48 Weeks

Study Arms (3)

Myelofibrosis (MF)

EXPERIMENTAL

18 patients with MF will be enrolled

Drug: Methotrexate (MTX)

Polycythemia vera (PV)

EXPERIMENTAL

18 patients with MF will be enrolled

Drug: Methotrexate (MTX)

Essential thrombocythemia (ET)

EXPERIMENTAL

18 patients with MF will be enrolled

Drug: Methotrexate (MTX)

Interventions

Methotrexate (MTX) DRUG

MTX has recently been identified as a dose-dependent JAK/STAT pathway inhibitor. 15mg will be given once a week orally.

Essential thrombocythemia (ET); Myelofibrosis (MF); Polycythemia vera (PV)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Must have received at least 12 weeks of current MPN therapy at stable doses and have persistent clinical burden and/or cytologic abnormalities as defined by the following:
• Clinical burden is defined as MPN-SAF TSS \>12 points and/or palpable spleen of ≥5cm
• Cytologic abnormalities include the following for each disease state:
• MF:
• Persistent leukocytosis as defined by WBC \>12 x 109/L
• PV:
• Persistent therapeutic phlebotomy dependence (\>2 phlebotomies within 24 weeks of screening, and \>1 phlebotomy within 16 weeks of screening, as defined in the PROUD-PV studies) for a goal HCT \<45% and/or
• Leukocytosis as defined by WBC \>12 x 109/L and/or
• Thrombocytosis defined as platelet count \>500 x 109/L
• ET:
• Persistent leukocytosis as defined by WBC \>12 x 109/L and/or

You may not qualify if:

• 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
• Have moderate or severe cardiovascular disease as defined by the following:
• Have cardiac disease, including a myocardial infarction within 6 months prior to study entry, unstable angina pectoris, New York Heart Association Class III/IV congestive heart failure, or uncontrolled hypertension
• Have documented major ECG abnormalities (not responding to medical treatments)
• Be an organ transplant recipient other than bone marrow transplant
• Presence of active serious infection
• Have a known history B, or untreated hepatitis C infection
• Have a known history of pulmonary fibrosis, interstitial pneumonitis
• Have a known history of chronic pericardial effusions, pleural effusions, or ascites
• Have a known history of cirrhosis, or current heavy alcohol consumption
• Have impairment of gastrointestinal function or gastrointestinal disease that could significantly alter the absorption of MTX, including any unresolved nausea, vomiting, or diarrhea \> CTCAE v5.0 grade 1
• Have known history of tuberculosis or severe fungal infection

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead

Study Sites (1)

Ruttenberg Treatment Center

New York, New York, 10029, United States

RECRUITING

MeSH Terms

Conditions

Polycythemia Vera; Thrombocythemia, Essential; Primary Myelofibrosis

Interventions

Methotrexate

Condition Hierarchy (Ancestors)

Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Blood Coagulation Disorders; Thrombocytosis; Blood Platelet Disorders; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• John Mascarenhas

  Icahn School of Medicine at Mount Sinai

  STUDY CHAIR

Central Study Contacts

Gabriela Bello

CONTACT

(212) 241-0463; gabriela.bello@mssm.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Model Details: Stage 1: 9 participants will be accrued to each of three cohorts of patients with MPNs: PV, ET, and MF. Low-dose, weekly MTX will be added to current therapy. If 0 responses occur within a given cohort, the study will be stopped within that cohort for futility; if ≥3 responses occur within a given cohort, the study will be stopped for early evidence of efficacy within that cohort. If 1-2 responses occur within any given cohort, that cohort will proceed to Stage 2. An additional 1 participant will be accrued to account for potential dropout. Stage 2: 9 additional participants will be accrued to each of three cohorts. If a total of \>3 of 20 participants enrolled achieve responses in any cohort, the study will be considered successful and MTX worthy of further study within that cohort. An additional 1 participant will be accrued to account for potential dropout.

Study Record Dates

• First Submitted: August 2, 2024
• First Posted: August 7, 2024
• Study Start: October 2, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: December 17, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months and ending 5 years following article publication.
• Access Criteria: Researchers who provide a methodologically sound proposal. To achieve aims in the approved proposal. Proposals should be directed to john.mascarenhas@mssm.edu. To gain access, data requestors will need to sign a data access agreement.

Locations

US (1)