ArthritisPhase 2NCT06001125
Methotrexate for Immune Related Arthritis or Arthralgias (IMPACT 2.1)
A Phase 2 study testing Methotrexate in people with Arthritis and Arthralgia, run by AHS Cancer Control Alberta at 1 site in Canada.
Trial summary
Many people develop joint pain, stiffness and swelling due to their cancer treatment that targets the immune system. The severity of symptoms ranges from mild to debilitating and sometimes requires delaying or stopping cancer treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Arthritis, Arthralgia
- What is being tested?
- Methotrexate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteCanada
- Study dates
- 12 Aug 2024to 7 Oct 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients who were previously on hydroxychloroquine treatment as standard of care therapy or enrolled in IMPACT 2.0 who develop recurrent grade ≥ 2 irAA, or who remain on glucocorticoids for irAA at 3 months will be eligible for this trial.
- Patients must be 18 years of age, or older.
- Patients must be capable of providing consent to enrolment and treatment.
- Patients with a performance status of ECOG 0-2 will be eligible for enrolment.
- Patients with histologically confirmed cancer receiving anti-PD1 or anti-PDL1 monoclonal antibody ICI therapy, either alone or in combination with anti-CTLA4 monoclonal antibody ICI therapy who develop CTCAEv5.0 grade ≥2 arthritis or arthralgia that has developed on, or after, ICI therapy and is felt to be treatment related (irAA).
- Adequate hematologic parameters defined by the following laboratory parameters:
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- Hgb >100 g/L
- Platelets>150 x 109/L
- WBC>Lower limit of normal
- Adequate hepatic and renal function defined by the following laboratory parameters:
- AST, ALT, bilirubin and alkaline phosphatase within normal range,
- Serum creatinine ≤ upper limit of institutional normal OR calculated creatinine clearance of ≥ 60 mL/min using the Cockcroft-Gault formula.
- Patients with an elevated bilirubin, but confirmed to have Gilbert's disease will be eligible
- Women of childbearing potential (WOCBP) must have a negative serum (or urine) pregnancy test at the time of screening. WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy or bilateral salpingectomy) and is not postmenopausal. Menopause is defined as 12 months of amenorrhea in a woman over age 45 years in the absence of other biological or physiological causes. In addition, females under the age of 55 years must have a serum follicle stimulating hormone, (FSH) level > 40 mIU/mL to confirm menopause.
- Patients of childbearing/reproductive potential should use highly effective birth control methods, during the study treatment period and for a period of 6 months after the last dose of study drug. A highly effective method of birth control is defined as those that result in low failure rate (i.e., less than 1% per year) when used consistently and correctly. These may include hormonal contraceptives (e.g., combined oral contraceptives, patch, vaginal ring, injectables, and implants); intrauterine device (IUD) or intrauterine system (IUS); vasectomy and tubal ligation. Double-barrier methods may be acceptable in circumstances when highly effective methods cannot be implemented (e.g., male condom with diaphragm, male condom with cervical cap). Note: Contraceptive requirements for the oncology regiments will apply, if they are more stringent than those for this trial. Abstinence is acceptable if this is established and preferred contraception for the patient.
- Female patients who are breast-feeding should discontinue nursing prior to the first dose of study treatment and until 6 months after the last dose of study drug.
- Male patients should agree to not donate sperm during the study and for a period of at least 6 months after last dose of study drug.
- Absence of any condition hampering compliance with the study protocol and follow- up schedule; those conditions should be discussed with the patient before registration in the trial.
Who cannot join
- History of inflammatory arthritis, including, but not limited to: Rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, Ankylosing spondylitis or other chronic inflammatory arthritis. Note: Patients with a known history of stable osteoarthritis will not be excluded.
- Patients with an indication for systemic immunosuppressive medications or corticosteroids. Patients with CTCAEv5.0 grade ≥2 irAE's other than irAA (ie. colitis, pneumonitis, rash, etc) are not eligible for trial, with the exception of endocrinopathies that are being treated with hormone replacement alone and not systemic immunosuppressive medications or corticosteroids.
- Patients with G6PD deficiency, porphyria or psoriasis.
- Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
- Diagnosis of immunodeficiency.
- Diagnosis of untreated hepatitis B and C.
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- Current use of immunosuppressive medication, EXCEPT for the following: prednisone and hydroxychloroquine per IMPACT 2.0 protocol or standard of care.
- Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (CTCAEv5.0 Grade ≥ 3).
- Excessive alcohol intake defined as greater than 7 units per week.
- Other severe acute or chronic medical conditions including inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities (see parameters in inclusion criteria) that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Study to Evaluate the Efficacy and Safety of Methotrexate in Immune Related Arthritis or Arthralgias
Many people develop joint pain, stiffness and swelling due to their cancer treatment that targets the immune system.
The severity of symptoms ranges from mild to debilitating and sometimes requires delaying or stopping cancer treatment.
Read more
The usual plan is to discontinue cancer treatment and give relatively high doses of a medication called prednisone (a steroid, which is an anti-inflammatory medication which may suppress the immune system), with a gradual lowering of the dose over several weeks.
While this can be effective, prednisone can cause several side effects, and it is not known if this is the best or safest treatment.
Hydroxychloroquine is a medication being studied on IMPACT 2.0 on participants who develop inflammatory joint pain while taking cancer treatments that affect their immune system. It is possible that the hydroxychloroquine treatment may not work well on some participants on IMPACT 2.0. Hydroxychloroquine is also given as standard of care to participants with this type of inflammatory joint pain.
The goal of this study is to learn how well methotrexate is at treating inflammatory joint pain in participants from IMPACT 2.0 that don't do well on treatment with hydroxychloroquine and in patients given hydroxychloroquine as standard of care to treat this type of inflammatory joint pain caused by taking cancer treatments which target their immune system.
- Conditions
- Arthritis, Arthralgia
- Being tested
- Methotrexate
- Medical subject headings
- Arthritis, Arthralgia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethotrexateDrug
Methotrexate 20 mg PO weekly
| Study group | Role | What they receive |
|---|---|---|
| Single Arm | Experimental | Methotrexate 20 mg PO weekly for 12 weeks.
Folic acid 1mg PO daily for as long as Methotrexate is given.
Prednisone starting at 20 mg PO daily for 8 weeks tapering dose. Receives: Drug: Methotrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Discontinuation of Prednisone
Proportion of patients who were able to discontinue prednisone by 12 weeks without recurrence of grade 2 or higher irAA.
Measured: 12 weeks
Secondary outcomes (5)
Total Steroid Usage
The total cumulative dose of prednisone measured in mg used by the participant. If corticosteroids other than prednisone are used, their equivalent dosage in mg of prednisone will be calculated and used for this analysis.
Measured: 12 weeks
Development of Immune Related Adverse Events (irAEs) Other Than irAA
Defined as the emergence of adverse events that were not present at study baseline that are deemed by the investigator to be related to prior use of immune checkpoint inhibitors. Causality will be investigator assessed and graded according to CTCAEv5.0
Measured: 12 weeks
Adverse Events
The emergence of new or worsening baseline symptoms, physical findings, or laboratory/imaging abnormalities. Causality to study treatment, immune checkpoint inhibitors, or underlying disease status will be investigator assessed and graded according to CTCAEv5.0.
Measured: 12 weeks
Re-initiation of Immune Checkpoint Inhibitor Therapy
The proportion of participants in each study arm that are re-treated with an immune checkpoint inhibitor.
Measured: 12 weeks
Progression Free Survival
The time elapsed between recruitment and tumor progression (radiographically or clinically) or death from any cause.
Measured: Time Frame: Total study observation period (3 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2023
- Study start12 Aug 2024
- Primary completion17 Jun 2025
- Study completion7 Oct 2025
Why it stopped: Challenges in meeting the enrollment target
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ArthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- AHS Cancer Control Alberta
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michael Kolinsky, Principal investigator, AHS-CCI
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06001125
- Sponsor's protocol ID
- IIT-0029
- Status last verified
- Jan 2026
- First submitted
- 4 Aug 2023
- Last updated
- 6 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study to Evaluate the Efficacy and Safety of Methotrexate in Immune Related Arthritis or Arthralgias
- ClinicalTrials.gov ID
- NCT06001125
- Acronym / sponsor ID
- IIT-0029
- Conditions
- Arthritis, Arthralgia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Challenges in meeting the enrollment target
- Enrolment
- 27 participants (actual)
- Lead sponsor
- AHS Cancer Control AlbertaUniversity, hospital or other
- Study start
- 12 Aug 2024 (actual)
- Primary completion
- 17 Jun 2025 (actual)
- Study completion
- 7 Oct 2025 (actual)
- First posted
- 21 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Many people develop joint pain, stiffness and swelling due to their cancer treatment that targets the immune system.
The severity of symptoms ranges from mild to debilitating and sometimes requires delaying or stopping cancer treatment.
The usual plan is to discontinue cancer treatment and give relatively high doses of a medication called prednisone (a steroid, which is an anti-inflammatory medication which may suppress the immune system), with a gradual lowering of the dose over several weeks.
While this can be effective, prednisone can cause several side effects, and it is not known if this is the best or safest treatment.
Hydroxychloroquine is a medication being studied on IMPACT 2.0 on participants who develop inflammatory joint pain while taking cancer treatments that affect their immune system. It is possible that the hydroxychloroquine treatment may not work well on some participants on IMPACT 2.0. Hydroxychloroquine is also given as standard of care to participants with this type of inflammatory joint pain.
The goal of this study is to learn how well methotrexate is at treating inflammatory joint pain in participants from IMPACT 2.0 that don't do well on treatment with hydroxychloroquine and in patients given hydroxychloroquine as standard of care to treat this type of inflammatory joint pain caused by taking cancer treatments which target their immune system.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single Arm | Experimental | Drug: MethotrexateMethotrexate 20 mg PO weekly for 12 weeks. Folic acid 1mg PO daily for as long as Methotrexate is given. Prednisone starting at 20 mg PO daily for 8 weeks tapering dose. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Patients who were previously on hydroxychloroquine treatment as standard of care therapy or enrolled in IMPACT 2.0 who develop recurrent grade ≥ 2 irAA, or who remain on glucocorticoids for irAA at 3 months will be eligible for this trial.
- Patients must be 18 years of age, or older.
- Patients must be capable of providing consent to enrolment and treatment.
- Patients with a performance status of ECOG 0-2 will be eligible for enrolment.
- Patients with histologically confirmed cancer receiving anti-PD1 or anti-PDL1 monoclonal antibody ICI therapy, either alone or in combination with anti-CTLA4 monoclonal antibody ICI therapy who develop CTCAEv5.0 grade ≥2 arthritis or arthralgia that has developed on, or after, ICI therapy and is felt to be treatment related (irAA).
Key exclusion criteria (10 listed)
- History of inflammatory arthritis, including, but not limited to: Rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, Ankylosing spondylitis or other chronic inflammatory arthritis. Note: Patients with a known history of stable osteoarthritis will not be excluded.
- Patients with an indication for systemic immunosuppressive medications or corticosteroids. Patients with CTCAEv5.0 grade ≥2 irAE's other than irAA (ie. colitis, pneumonitis, rash, etc) are not eligible for trial, with the exception of endocrinopathies that are being treated with hormone replacement alone and not systemic immunosuppressive medications or corticosteroids.
- Patients with G6PD deficiency, porphyria or psoriasis.
- Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
- Diagnosis of immunodeficiency.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MethotrexateMethotrexate 20 mg PO weekly | Drug | Single Arm |
Primary outcome
Discontinuation of Prednisone
Time frame: 12 weeks
Proportion of patients who were able to discontinue prednisone by 12 weeks without recurrence of grade 2 or higher irAA.
5 secondary outcomes
Total Steroid Usage
Time frame: 12 weeks
Development of Immune Related Adverse Events (irAEs) Other Than irAA
Time frame: 12 weeks
Adverse Events
Time frame: 12 weeks
Re-initiation of Immune Checkpoint Inhibitor Therapy
Time frame: 12 weeks
Progression Free Survival
Time frame: Time Frame: Total study observation period (3 years)
Results and safety
The study was stopped early (reason given: Challenges in meeting the enrollment target). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Kolinsky principal investigator
AHS-CCI
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Methotrexate in people with Arthritis and Arthralgia, run by AHS Cancer Control Alberta at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 6 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Challenges in meeting the enrollment target). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Discontinuation of Prednisone (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2026.