Leflunomide for Solid Tumors

Overseen By Natalie Lucas, NP

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Deborah Doroshow

Must not be taking: Investigational agents

Disqualifiers: Primary CNS tumors, Hepatitis B/C, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 month

24 Participants Needed

Trial Summary

What is the purpose of this trial?

Leflunomide in patients with PTEN-null advanced solid tumors. Objectives are to determine the safety and tolerability and the MTD of leflunomide in patients with PTEN-null advanced solid malignancies and to assess preliminary evidence of clinical activity of leflunomide in patients with PTEN-null advanced solid malignancies.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must be at least 4 weeks from your last systemic therapy, surgery, or radiation. You also cannot be on any other investigational agents.

What makes the drug Leflunomide unique for treating solid tumors?

Leflunomide is unique for treating solid tumors because it is primarily known as an immunosuppressive drug for rheumatoid arthritis, but its metabolite LFM-A13 is being developed as a novel anticancer drug with properties that promote cell death and prevent blood clots, which is different from standard cancer treatments. ^{1 2 3 4 5}

Research Team

Deborah Doroshow, MD, PhD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

Adults with advanced solid tumors lacking PTEN protein, as confirmed by a specific test. They must have measurable disease, be at least 4 weeks out from prior treatments, and not require immediate brain metastasis treatment. Participants need to be in fair health (ECOG 0-2), have good organ function, and agree to use contraception. Those with HIV can join if their viral load is undetectable.

Inclusion Criteria

Patients must have measurable disease per RECIST 1.1 criteria

My cancer did not respond or worsened after standard treatment, or I couldn't tolerate it.

My doctor thinks I don't need immediate brain treatment for my cancer.

Exclusion Criteria

I do not have a primary brain tumor.

I haven't had chemotherapy or radiotherapy in the last 4 weeks and have recovered from most side effects.

I have a history of Hepatitis B or C.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Leflunomide, 20-50mg PO daily to determine safety, tolerability, and MTD

1 month

Dose Expansion

Participants are monitored for overall response rate using RECIST v1.1

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Leflunomide

Trial Overview The trial tests Leflunomide's safety and maximum tolerated dose in patients whose tumors don't express the PTEN protein. It also looks for any signs that the drug might help control the cancer.

Participant Groups

Group I: Leflunomide Experimental Treatment 1 Intervention

Leflunomide, 20-50mg PO daily

Leflunomide is already approved in European Union, United States, United Kingdom for the following indications:

Approved in European Union as Arava for:

• Rheumatoid arthritis
• Psoriatic arthritis

Approved in United States as Arava for:

• Rheumatoid arthritis
• Psoriatic arthritis

Approved in United Kingdom as Arava for:

• Rheumatoid arthritis
• Psoriatic arthritis

Who Is Running the Clinical Trial?

Deborah Doroshow

Lead Sponsor

Trials

1

Recruited

20+

Findings from Research

In a study of 7 pediatric kidney transplant patients, leflunomide effectively controlled BK virus viremia, with 67% achieving complete viral clearance, even with reduced immunosuppressive therapy.

No serious adverse effects like graft rejection or hepatotoxicity were observed, although some patients experienced mild issues like hemolytic anemia and pancreatitis, suggesting leflunomide may be a safe option for managing BK virus in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Leflunomide for BKvirus: Report of Seven Kidney-Transplanted Children. Launay, M., Baudouin, V., Guillemain, R., et al.[2022]

A 64-year-old woman developed a lichenoid drug reaction after two months of treatment with leflunomide for rheumatoid arthritis, indicating a potential adverse effect of this immunomodulator.

The reaction improved significantly after stopping the medication and using colestyramine and topical corticosteroids, suggesting that leflunomide can cause serious skin reactions, although such side effects are generally rare and benign.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Lichenoid drug reaction to leflunomide]. Canonne-Courivaud, D., Carpentier, O., Dejobert, Y., et al.[2018]

Leflunomide shows significant immunosuppressive effects in liver and kidney transplant recipients, allowing for reductions in conventional immunosuppressive drugs like cyclosporine and prednisone without evidence of acute rejection.

The drug was well tolerated in patients with lower serum creatinine levels, but those with higher levels experienced more side effects, highlighting the importance of monitoring serum drug levels for safe and effective dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experiences with leflunomide in solid organ transplantation. Williams, JW., Mital, D., Chong, A., et al.[2022]

LFM-A13, a metabolite analog of leflunomide, is a designed inhibitor of Bruton's tyrosine kinase (BTK) and shows potential as a dual-function anticancer drug with both apoptosis-promoting and anti-thrombotic properties.

The drug was produced under current Good Manufacturing Practice (cGMP) conditions, ensuring its quality and safety for further development and testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Large-scale synthesis of GMP grade alpha-cyano-beta-hydroxy-beta-methyl-N-(2,5-dibromophenyl) propenamide (LFM-A13), a new anti-cancer drug candidate. DuMez, D., Venkatachalam, TK., Uckun, FM.[2013]

In a study of 32 sarcoidosis patients, leflunomide was found to be effective, with a complete or partial response in 12 out of 17 patients treated with leflunomide alone and 13 out of 15 patients receiving it alongside methotrexate.

Leflunomide was well tolerated, with only three patients experiencing nausea, and no serious adverse reactions reported, suggesting it may be a safer alternative to methotrexate for patients who cannot tolerate it.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Leflunomide for chronic sarcoidosis. Baughman, RP., Lower, EE.[2019]

References

1. Iran pubmed.ncbi.nlm.nih.gov

Leflunomide for BKvirus: Report of Seven Kidney-Transplanted Children. [2022]

2. France pubmed.ncbi.nlm.nih.gov

[Lichenoid drug reaction to leflunomide]. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Experiences with leflunomide in solid organ transplantation. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Large-scale synthesis of GMP grade alpha-cyano-beta-hydroxy-beta-methyl-N-(2,5-dibromophenyl) propenamide (LFM-A13), a new anti-cancer drug candidate. [2013]

5. Italy pubmed.ncbi.nlm.nih.gov

Leflunomide for chronic sarcoidosis. [2019]