Response-Adapted Therapy With Copanlisib and Rituximab in Untreated Follicular Lymphoma
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|ClinicalTrials.gov Identifier: NCT03789240|
Recruitment Status : Recruiting
First Posted : December 28, 2018
Last Update Posted : November 4, 2019
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.
To see if copanlisib plus rituximab is effective at slowing the growth of FL.
People with FL who have not had prior treatment for their disease
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.
|Condition or disease||Intervention/treatment||Phase|
|Follicular Lymphoma Non-Hodgkin's Lymphoma NHL||Biological: Rituximab Drug: Copanlisib||Phase 2|
- 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
- To determine the complete response (CR) rate after copanlisib and rituximab as induction therapy for patients with untreated follicular lymphoma
- 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
- 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
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||65 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2 Study of Response-Adapted Therapy With Copanlisib and Rituximab in Untreated Follicular Lymphoma|
|Actual Study Start Date :||August 22, 2019|
|Estimated Primary Completion Date :||January 1, 2027|
|Estimated Study Completion Date :||January 1, 2027|
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.
Rituximab is administered at a dose of 375 mg/m^2 via IV weekly for the first 4 weeks on Days 1, 8, 15, and 22 during cycle 1. With subsequent cycles (cycles 2-6), rituximab will be dosed only once on Day 1 of the cycle.
Copanlisib is administered at a fixed dose of 60 mg via IV weekly for the first 3 weeks on Days 1, 8, and 15 followed by a 1-week break (no infusion on Day 22)
- Acheivement of complete response [ Time Frame: Within 6 months of induction therapy completion ]The response rate will be determined and reported along with a 95% confidence interval
- Safety of study treatments when given in combination [ Time Frame: Through study induction therapy period ]Incidence of adverse events
- Continuous complete response rate [ Time Frame: At 30 months from study enrollment ]The response rate will be determined and reported along with a 95% confidence interval
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03789240
|Contact: Maureen E Edgerly, R.N.||(240) 760-6013||NCIMO_Referrals@mail.nih.gov|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937|
|Principal Investigator:||Mark J Roschewski, M.D.||National Cancer Institute (NCI)|