Response-Adapted Therapy With Copanlisib and Rituximab in Untreated Follicular Lymphoma
- Conditions
- Follicular LymphomaNon-Hodgkin's LymphomaNHL
- Interventions
- Registration Number
- NCT03789240
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief 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.
...
- Detailed 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
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 33
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description 1 Rituximab Window of treatment with Copanlisib 60mg via IV for a single 28 day cycle, once weekly for the first 3 weeks and then a 1 week break followed by induction therapy with copanlisib and rituximab. Induction therapy will be 6 cycles (28 days) of: copanlisib dose and administration same as window, rituximab 375mg/m2 via IV, once weekly for the first 4 weeks during cycle 1, subsequent cycles (cycles 2-6), rituximab will be dosed only once on day 1 of the cycle. 1 Copanlisib Window of treatment with Copanlisib 60mg via IV for a single 28 day cycle, once weekly for the first 3 weeks and then a 1 week break followed by induction therapy with copanlisib and rituximab. Induction therapy will be 6 cycles (28 days) of: copanlisib dose and administration same as window, rituximab 375mg/m2 via IV, once weekly for the first 4 weeks during cycle 1, subsequent cycles (cycles 2-6), rituximab will be dosed only once on day 1 of the cycle.
- Primary Outcome Measures
Name Time Method Acheivement of complete response Within 6 months of induction therapy completion The response rate will be determined and reported along with a 95% confidence interval
- Secondary Outcome Measures
Name Time Method Safety of study treatments when given in combination Through study induction therapy period Incidence of adverse events
Continuous complete response rate At 30 months from study enrollment The response rate will be determined and reported along with a 95% confidence interval
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States