Methotrexate for Immune Related Arthritis or Arthralgias (IMPACT 2.1)

NCT06001125 | Terminated Phase 2 DMC

• 1 other identifier: IIT-0029
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief 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. 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

Outcome Measures

Primary Outcomes (1)

• Discontinuation of Prednisone

  Proportion of patients who were able to discontinue prednisone by 12 weeks without recurrence of grade 2 or higher irAA.

  12 weeks

Secondary Outcomes (5)

• Total Steroid Usage

  12 weeks

• Development of Immune Related Adverse Events (irAEs) Other Than irAA

  12 weeks

• Adverse Events

  12 weeks

• Re-initiation of Immune Checkpoint Inhibitor Therapy

  12 weeks

• Progression Free Survival

  Time Frame: Total study observation period (3 years)

Other Outcomes (6)

• Musculoskeletal Ultrasound of Symptomatic Joints

  Performed at baseline and Week 13 Day1 (to align with 12- month MSK Ultrasound of IMPACT 2.0). Analysis will be done to compare baseline to Wk13D1.

• RAPID 3 Questionnaire

  Performed at screening, baseline, Week 3 Day 1, Week 5 Day 1, Week 7 Day 1, Week 9 Day 1, Week 11 Day 1, Week 13 Day 1, and at 6 and 12 month follow up.

• Bone Turnover Markers

  Collected at baseline, Week 13 Day 1

Study Arms (1)

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.

Drug: Methotrexate

Interventions

Methotrexate DRUG

Methotrexate 20 mg PO weekly

Single Arm

Eligibility Criteria

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

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• AHS Cancer Control Alberta: lead

Study Sites (1)

Cross Cancer Institute

Edmonton, Canada

Location

MeSH Terms

Conditions

Arthritis; Arthralgia

Interventions

Methotrexate

Condition Hierarchy (Ancestors)

Joint Diseases; Musculoskeletal Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Officials

• Michael Kolinsky

  AHS-CCI

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2023
• First Posted: August 21, 2023
• Study Start: August 12, 2024
• Primary Completion: June 17, 2025
• Study Completion: October 7, 2025
• Last Updated: January 6, 2026

Record last verified: 2026-01

Locations

CA (1)