Response-Adapted Therapy With Copanlisib and Rituximab in Untreated Follicular Lymphoma

Non-Hodgkin's Lymphoma Clinical Trial

Official title: A Phase 2 Study of Response-Adapted Therapy With Copanlisib and Rituximab in Untreated Follicular Lymphoma

Status Active, not recruiting

Clinical Trial Summary

Background: The disease follicular lymphoma (FL) develops when the body makes abnormal B-cells. These cells usually build up in the lymph nodes, but can also affect other parts of the body. Researchers want to see if a combination of drugs can attack the cancer cells in people with FL. Objective: To see if copanlisib plus rituximab is effective at slowing the growth of FL. Eligibility: People with FL who have not had prior treatment for their disease Design: Participants will be screened with: - Medical and cancer history - Physical exam - Review of symptoms and ability to perform daily activities - Blood and urine tests - Small amount of bone marrow removed by needle in the hip bone - Scans of the chest, abdomen, and pelvis. Some scans will use a radioactive tracer. Participants will get the study drugs in 28-day cycles for up to 13 cycles. Both are given as an intravenous (IV) infusion. Copanlisib is given over about 1 hour. Rituximab is given over several hours. - For 1 cycle, they will get 3 weekly doses of copanlisib. - For the next cycle, they will get 3 weekly doses of copanlisib and 4 weekly doses of rituximab. - For all other cycles, they will get 2-3 weekly doses of copanlisib and 1 dose of rituximab. Participants will repeat some screening tests during the cycles. They will give a cheek swab and/or saliva sample and may have a tumor sample taken. After treatment, some participants will have a few follow-up visits each year for 5 years, then 1 each year. They will repeat screening tests. Other participants will be contacted by phone every few months.

Clinical Trial Description

Background: - Follicular lymphoma (FL) is the most common indolent non-Hodgkin s lymphoma (NHL) with a highly variable clinical course across patients - Standard frontline therapy for FL includes a monoclonal anti-CD20 antibody with or without chemotherapy that can induce durable remissions but is generally not curable - The 20% of patients who relapse within 2 years of frontline chemotherapy have an inferior overall survival; molecular profiles and gene-expression signatures can identify patients at high-risk of early treatment failure but are incomplete and require further validation - The phosphoinositide 3-kinase (PI3K) pathway is critically important in FL; agents that target PI3K show good clinical activity in patients who relapse early after chemotherapy - Copanlisib is an intravenous therapy targeting both PI3K-alpha and PI3K-delta isoforms and is FDA-approved for use in adults with relapsed and refractory FL - Induction therapy with copanlisib and rituximab may produce deep and durable remissions in patients with FL without the use of cytotoxic agents - Circulating tumor DNA (ctDNA) is a promising modality for monitoring therapy Objective: - To determine the complete response (CR) rate after copanlisib and rituximab as induction therapy for patients with untreated follicular lymphoma Eligibility: - Patients with histologically confirmed stage II-IV follicular lymphoma, grade 1-2 or 3a that meet criteria for initiation of systemic therapy - No previous systemic therapy; prior local radiation permitted - ECOG performance status 0-2 - Adequate bone marrow and organ function Design: - Phase 2 study of up to 65 patients with untreated FL who meet standard criteria for treatment - Patients will first be treated with a window of copanlisib monotherapy, followed by induction therapy with copanlisib and rituximab for up to 6 cycles - Patients who achieve a CR after 6 cycles of induction therapy will stop treatment and be monitored with computed tomography (CT) scans and plasma assays for circulating tumor DNA (ctDNA). Patients who relapse > 6 months from the end of induction can be re-treated with 6 additional cycles of copanlisib and rituximab - Patients who achieve a partial response after 6 cycles of induction therapy will receive an additional 6 cycles of extended induction therapy with copanlisib and rituximab - Patients who do not achieve at least a partial response after 6 cycles of induction therapy will stop treatment and be monitored with CT scans and peripheral blood assays for ctDNA - Patients who progress or relapse after induction therapy and meet criteria for salvage therapy will be treated with standard chemotherapy and a monoclonal anti-CD20 antibody ;

Related Conditions & MeSH terms

• Follicular Lymphoma
• Lymphoma
• Lymphoma, Follicular
• NHL
• Non-Hodgkin's Lymphoma

• NCT number: NCT03789240
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 22, 2019
• Completion date: January 1, 2027