Clinical Trials for Rare and Common Hematology Disorders Ongoing in Florida

Hematologists at Cleveland Clinic Florida’s Maroone Cancer Center have three late-stage clinical trials ongoing for rare and common blood disorders: AL (light chain) amyloidosis, paroxysmal nocturnal hemoglobinuria (PNH), and immune thrombocytopenia (ITP).

“Conducting clinical research to improve care for the small patient populations impacted by rare blood disorders is exceptionally challenging,” notes Chieh-Lin Fu, MD, Head of the Section of Hematology at Cleveland Clinic Florida, who leads a team of experts in malignant and benign hematologic disorders focused on advancing care through research. “That is why it is so important that we can bring these international, multicenter phase 3 studies to Florida. Ultimately, it is our hope that we can help our patients and many more.”

AL Amyloidosis

Approximately 4,000 new cases of AL amyloidosis are diagnosed in the U.S. each year. This rare and often misdiagnosed hematologic disorder begins in the bone marrow where abnormal proteins produced by cancerous plasma cells misfold and create insoluble free light chains that cannot be broken down. These proteins clump together and form amyloid deposits that build up and deposit in vital organs such as heart, kidneys, liver and gastrointestinal tract causing organ damage leading to organ failure over time. Multiple organs can be impacted but it most commonly effects the heart and kidneys leading to heart failure and kidney damage.

“Amyloidosis can cause significant organ damage, so the sooner we diagnose and begin treatment, the better,” says Chakra Chaulagain, MD, FACP, a hematologist at Cleveland Clinic Weston Hospital who specializes in the treatment of amyloidosis and plasma cell disorders, such as multiple myeloma. “Cardiac involvement is the key determinant of survival for patients with AL amyloidosis as it can lead to congestive heart failure and early death if left untreated.”

Dr. Chaulagain is the principal investigator for the only South Florida site of the international, multicenter phase 3 study that is evaluating the effectiveness and safety of CAEL-101, a fibril-reactive monoclonal antibody, in patients with Mayo Stage IIIa and Stage IIIb AL amyloidosis. Approximately 267 patients will be enrolled across approximately 100 investigator sites, and Cleveland Clinic Florida is currently open to enroll patients.

“While chemotherapy is used to stop production of the amyloid precursor protein in the bone marrow, we do not currently have an approved treatment for eliminating the pre-existing amyloid deposits in the affected organs such as heart and kidneys often present at the time of diagnosis due to a delay in diagnosis,” explains Dr. Chaulagain, who is part of a multidisciplinary team at Cleveland Clinic Florida’s Cardiac Amyloidosis Center. “This study will determine if CAEL-101 improves the overall survival in patients with cardiac AL amyloidosis by breaking down the amyloid fibrils.”

Paroxysmal Nocturnal Hemoglobinuria

With an estimated prevalence of 0.5-1.5 per million people, paroxysmal nocturnal hemoglobinuria (PNH) is another rare hematologic disease treated by the specialists at Cleveland Clinic Florida. This hematopoietic stem cell disorder occurs when an acquired genetic mutation produces defective red blood cells that break down prematurely resulting in hemoglobinuria. Patients may experience hemolytic anemia, impaired bone marrow function, and potentially life-threatening thromboses.

Cleveland Clinic Florida is currently participating in a multicenter, international phase 3 study that is evaluating the efficacy of danicopan, an oral complement alternative pathway factor D inhibitor, as an add-on therapy to a C5 inhibitor (eculizumab or ravulizumab) in patients with PNH who have clinically evident extravascular hemolysis (EVH).

“While C5 inhibitors can stop PNH-related intravascular hemolysis, it does not address extravascular hemolysis that can occur primarily in the spleen and liver,” says Dr. Fu, principal investigator for the Weston site. “Danicopan is designed to control both types of hemolysis and thus may help patients who have an inadequate response to the C5 inhibitor alone.”

Primary Immune Thrombocytopenia

Compared to AL amyloidosis and PNH, primary immune thrombocytopenia (ITP) is a relatively common hematologic disorder that affects an estimated 3 in 100,000 adults per year. The acquired bleeding disorder is caused by the targeted destruction of platelets by the body’s immune cells. Clinical features of ITP range from petechiae, mucosal bleeding, and easy bruising to internal bleeding and hemorrhagic stroke.

Cleveland Clinic Florida is the only Florida site participating in the international, multicenter phase 3 study evaluating the efficacy and safety of efgartigimod (ARGX-113) PH20 subcutaneous in adult patients with chronic ITP. Efgartigimod is a neonatal Fc receptor (FcRn) blocker shown to reduce the levels of pathogenic immunoglobulin G (IgG) autoantibodies and is currently FDA-approved in the use of myasthenia gravis.

“While we have a number of ITP-targeted therapies today, there remains a population of patients with chronic ITP that is refractory to conventional agents,” says Dr. Fu, who also serves as principal investigator for the ITP study. “It is our hope that this novel agent, which works differently from other drugs to calm the immune response, can improve platelet counts and reduce bleeding risk in patients with severe and symptomatic low platelet count.”

To refer a patient for participation in a clinical trial at Cleveland Clinic Florida, visit clevelandclinicflorida.org/cancerresearch or contact lews2@ccf.org.