City of Hope Doctors Lead Novel Clinical Trial to Treat Cancer Patients with COVID-19
2 September 2020 - - California, US-based cancer center City of Hope is investigating an innovative treatment for cancer patients with COVID-19 by repurposing leflunomide, an anti-inflammatory drug for rheumatoid arthritis that is inexpensive and has few serious side effects, in a new clinical trial, the organization said.

Patients treated for cancer in the past two years may also be eligible, City of Hope said. The US Food and Drug Administration recently approved the start of a phase 1 trial.

At a later date, a phase 2 randomized clinical trial may take place if the first trial finds leflunomide to be safe and tolerable for these patients.

City of Hope plans to work with other local medical centers who are treating cancer patients for SARS-CoV-2, the virus that causes COVID-19, to enroll them in the trial.

For the phase 1 trial, all patients will receive leflunomide and may also be able to simultaneously receive other standard of care treatments for COVID-19.

They may receive remdesivir, an antiviral therapy. Patients with acute respiratory distress syndrome may receive the steroid, dexamethasone, and patients with complications of COVID-19 such as cytokine release syndrome, which can lead to multiple organ failure, can receive the antibody tocilizumab.

As a comprehensive cancer center, city of Hope has extensive experience treating patients with these therapies, including tocilizumab, which is used to treat CRS in patients who receive chimeric antigen receptor T cell therapy. The institution is in deliver CAR T therapy.

If the phase 1 trial is found to be a safe and tolerable treatment, then a phase 2 randomized, double-blind trial will open at a later date.

About half the patients will receive leflunomide with standard of care therapies to treat COVID-19, and the other half will receive a placebo and standard of care drugs as well.

Leflunomide is an oral and generic anti-inflammatory drug approved by the FDA to safely treat autoimmune diseases such as rheumatoid arthritis. The therapy has also been used in cancer patients with cytomegalovirus with tolerable side effects.

Laboratory experiments performed at city of Hope and Wuhan, China, indicate that leflunomide has high potential to shut down viral replication by preventing the synthesis of viral RNA, the genetic material. It also downregulates the expression of ACE 2, a receptor for COVID-19 cell entry.

A small clinical trial using leflunomide in China also demonstrated the therapy has potential antiviral drug against COVID-19.

In a phase 1 clinical trial, city of Hope treated patients with advanced multiple myeloma with leflunomide. The therapy stabilized their disease with tolerable side effects.

The National Cancer Institute has funded the trial with a P30 grant supplement for COVID-19 research projects.

City of Hope is one of a few cancer centers that has received such funding during the pandemic.
city of Hope also received generous funding from private donors, including The Elias, Genevieve and Georgianna Atol Charitable Trust and The Norman and Sadie Lee Foundation.

City of Hope is an independent biomedical research and treatment center for cancer, diabetes and other life-threatening diseases.

Founded in 1913, City of Hope is in bone marrow transplantation and immunotherapy such as CAR T cell therapy. city of Hope's translational research and personalized treatment protocols advance care throughout the world.