Methotrexate for Myeloproliferative Disorders
(TREATMORE Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Icahn School of Medicine at Mount Sinai
Must be taking: Ruxolitinib
Must not be taking: MTX
Disqualifiers: Cardiovascular disease, Invasive malignancies, others
No Placebo Group
Prior Safety Data
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of 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.
Will I have to stop taking my current medications?
The trial does not require you to stop your current medications. In fact, it allows you to continue certain therapies like aspirin, hydroxyurea, and ruxolitinib, as long as they have been stable for at least 12 weeks.
What data supports the effectiveness of the drug Methotrexate for treating myeloproliferative disorders?
Methotrexate is known to be effective in treating rheumatoid arthritis by improving the efficacy of other treatments and is well-tolerated, which suggests it might be beneficial for other conditions like myeloproliferative disorders.
12345Is methotrexate generally safe for humans?
Methotrexate is generally considered safe for use in humans, especially in low doses for conditions like rheumatoid arthritis. However, serious side effects like pancytopenia (a decrease in blood cells) and rare cases of leukemia have been reported, often linked to interactions with other medications or specific health conditions.
46789How is the drug methotrexate unique for treating myeloproliferative disorders?
Methotrexate is unique because it was originally discovered for treating childhood leukemia and is now a standard treatment for rheumatoid arthritis, showing its versatility in treating different conditions. Its use in myeloproliferative disorders may offer a novel approach, as there are no standard treatments specifically for these conditions.
34101112Eligibility Criteria
The TREATMORE trial is for patients with myeloproliferative disorders such as myelofibrosis, essential thrombocythemia, or polycythemia vera. Participants should be currently receiving therapy for their condition but are still looking for additional treatment options.Inclusion Criteria
Must voluntarily sign ICF and be willing and able to adhere to the study visit schedule and all protocol requirements
I agree to use birth control during the study.
My myelofibrosis is classified from low to high-risk, or I have polycythemia vera or essential thrombocythemia of any risk level.
+7 more
Exclusion Criteria
I haven't had any cancer except for skin, prostate, or cervical cancer in the last 3 years.
I have moderate or severe heart disease.
I have not had a heart attack or stroke in the last 6 months.
+14 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive low-dose Methotrexate in addition to current therapy for Myeloproliferative Neoplasms
48 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
This study tests low-dose Methotrexate (MTX), a medication traditionally used in rheumatologic diseases and recently identified as a type 2 JAK inhibitor. The trial will assess its safety, tolerability, and effectiveness when added to current therapies in MPNs.
3Treatment groups
Experimental Treatment
Group I: Polycythemia vera (PV)Experimental Treatment1 Intervention
18 patients with MF will be enrolled
Group II: Myelofibrosis (MF)Experimental Treatment1 Intervention
18 patients with MF will be enrolled
Group III: Essential thrombocythemia (ET)Experimental Treatment1 Intervention
18 patients with MF will be enrolled
Methotrexate is already approved in United States, Canada, European Union for the following indications:
🇺🇸 Approved in United States as Trexall for:
- Acute lymphoblastic leukemia
- Non-Hodgkin's lymphoma
- Osteosarcoma
- Breast cancer
- Lung cancer
- Head and neck cancer
- Psoriasis
- Rheumatoid arthritis
🇨🇦 Approved in Canada as Mexate for:
- Acute lymphoblastic leukemia
- Non-Hodgkin's lymphoma
- Osteosarcoma
- Breast cancer
- Lung cancer
- Head and neck cancer
- Psoriasis
- Rheumatoid arthritis
🇪🇺 Approved in European Union as Methotrexate for:
- Acute lymphoblastic leukemia
- Non-Hodgkin's lymphoma
- Osteosarcoma
- Breast cancer
- Lung cancer
- Head and neck cancer
- Psoriasis
- Rheumatoid arthritis
- Crohn's disease
- Ulcerative colitis
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Ruttenberg Treatment CenterNew York, NY
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Who Is Running the Clinical Trial?
Icahn School of Medicine at Mount SinaiLead Sponsor
References
Methotrexate Enhances Apoptosis of Transmembrane TNF-Expressing Cells Treated With Anti-TNF Agents. [2021]Concomitant use of methotrexate (MTX) improves the clinical efficacy of anti-TNF agents in the treatment of rheumatoid arthritis (RA). We aimed to clarify the cytotoxic effect of MTX on transmembrane TNF (tmTNF)-expressing cells treated with anti-TNF agents.
Methotrexate monotherapy versus methotrexate combination therapy with non-biologic disease modifying anti-rheumatic drugs for rheumatoid arthritis. [2022]Methotrexate (MTX) is among the most effective disease modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) with less toxicity and better tolerability.
Severe pancytopenia in a patient taking low dose methotrexate and probenecid. [2013]A patient with rheumatoid arthritis developed life-threatening pancytopenia resulting from low dose oral methotrexate (MTX) toxicity potentiated by probenecid. Clinically significant drug interactions are not frequently cited as risk factors for MTX hematologic toxicity. As low dose MTX is gaining increasing popularity in rheumatologic practice, these potentially serious interactions should be considered.
Temporal association between the use of methotrexate and development of leukemia in 2 patients with rheumatoid arthritis. [2013]To date only a single case of leukemia coincident with the use of methotrexate (MTX) in rheumatoid arthritis (RA) has been reported. We report 2 additional patients with RA, each of whom developed leukemia after receiving short term low dose MTX. Whether these cases represent an adverse effect of MTX treatment has yet to be determined.
[Combination therapy using methotrexate with DMARDs or biologics--current status]. [2021]Methotrexate (MTX) is the most frequently used drug in combination treatment with disease-modifying antirheumatic drugs (DMARDs) and biologics in rheumatoid arthritis. DMARD combinations are usually the second step after unsuccessful MTX monotherapy. Evidence-based combinations of MTX+leflunomide, MTX+cyclosporine and triple combination MTX+sulphasalazine+hydroxychloroquine (complemented by glucocorticoids) showed the best results.In the case of insufficient response to the DMARD combination, MTX should be used in combination with a biologic. To date, the most frequent biologic treatment is with TNF inhibitors, but studies have shown that all biologics (with the exception of Anakinra) have comparable success rates. The combination of MTX plus abatacept, MTX plus rituximab and MTX plus tocilizumab are very promising, both clinically and in terms of blocking radiological progression. The efficacy of biological therapy is generally better using MTX combination than monotherapy.The safety of MTX combination treatment with DMARDs is not significantly lower than that of the individual substances; therefore, the required safety controls are also the same.
Acute myeloid leukemia in the setting of low dose weekly methotrexate therapy for rheumatoid arthritis. [2019]Methotrexate is in widespread use as second-line therapy for rheumatoid arthritis. Treatment with methotrexate in this and other settings has not been associated with the development of therapy-related leukemias. Four patients with rheumatoid arthritis are reported who developed acute myeloid leukemia (AML) while receiving low dose weekly methotrexate therapy in the absence of previous or concomitant treatment with known leukemogenic agents. AML in these four patients was of different morphologic subtypes and was associated with heterogeneous cytogenetic abnormalities, cell surface marker expression and multidrug resistance protein expression. None of the recognized features of therapy-related leukemia were present in these four nor in five previously-reported patients. It is likely that the occurrence of AML in patients with rheumatoid arthritis in the setting of methotrexate therapy represents the coincidence of these two diseases, and does not reflect a causal relationship.
[Pancytopenia during low-dosage methotrexate treatment in patients with rheumatoid arthritis]. [2013]Adverse effects are no more common during treatment with low doses of methotrexate than during treatment with conventional anti-rheumatic drugs. Serious events do occur, however, and among the most dangerous is pancytopenia. We describe five patients with this complication. Triggering factors for such adverse events are often interactions with other medication, especially drugs that reduce renal clearance of methotrexate, and also other anti-folate drugs, e.g. trimetoprim. Events that increase the rate of cell formation in the myelopoietic tissue, e.g. infection and haemorrhage, may also increase risk of complications. Use of leukovorin is recommended when bone marrow suppression is suspected.
Acute leukemia after low dose methotrexate therapy in a patient with rheumatoid arthritis. [2013]An 83-year-old woman with seropositive rheumatoid arthritis (RA) developed acute myeloid leukemia after receiving weekly methotrexate (MTX) for 33 months (total dose 690 mg). Although cytogenetic abnormalities typical of damage by cytotoxic agents were not documented, our case may be the first report of acute myeloid leukemia in RA with MTX. We estimate that 6 similar cases should have been observed in France by chance alone. The absence of other reports suggests either that MTX possesses a paradoxical protective effect or that it is not considered a risk factor for malignancy by rheumatologists. Since the number of patients with RA taking MTX can be estimated with reasonable accuracy, the reporting of all suspected cases could help to assess the safety of the drug in rheumatology.
Methotrexate in rheumatoid arthritis: optimizing therapy among different formulations. Current and emerging paradigms. [2018]Methotrexate (MTX) is currently considered the drug of choice, among the disease-modifying antirheumatic drugs, for the treatment of rheumatoid arthritis (RA) because of its favorable risk/benefit ratio, good safety profile, and low costs. Despite MTX's widespread use and large experience accumulated over the many years since its introduction into clinical practice, specific guidelines have not been published.
Comparing Healthcare Costs Associated with Oral and Subcutaneous Methotrexate or Biologic Therapy for Rheumatoid Arthritis in the United States. [2022]Methotrexate (MTX) is the primary disease-modifying antirheumatic drug used for the treatment of rheumatoid arthritis (RA). Optimizing the use of oral and subcutaneous MTX may delay the use of expensive biologic therapies; the effect of such a delay on overall medical costs is currently unknown.
Landmark papers on the discovery of methotrexate for the treatment of rheumatoid arthritis and other systemic inflammatory rheumatic diseases: a fascinating story. [2017]This review highlights the story of how methotrexate (MTX), a drug discovered for the treatment of childhood leukemia, became the mainstay of treatment and the standard-of-care for rheumatoid arthritis (RA) and was also found useful for several additional related rheumatological diseases. As against several synthetic disease-modifying antirheumatic drugs (csDMARDs) for treating RA that were discovered serendipitously, the use of low-dose MTX (LD-MTX) was based on sound reasoning and astute observations made in the 1940s and 1950s. The difference between high-dose MTX (HD-MTX) used in the treatment of childhood leukaemia and other malignancies as against LD-MTX used in rheumatology is emphasized.
Severe pancytopenia associated with low-dose methotrexate therapy for rheumatoid arthritis. [2017]To report the occurrence of severe pancytopenia associated with low-dose methotrexate (MTX) therapy for rheumatoid arthritis.