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