Copanlisib + Rituximab for Follicular Lymphoma

Overseen By Mark J Roschewski, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Corticosteroids, Immunosuppressive drugs

Disqualifiers: CNS involvement, HIV, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if two drugs, copanlisib and rituximab, can effectively slow the growth of follicular lymphoma, a cancer involving abnormal B-cells in the lymph nodes. Participants will receive these drugs through an IV in cycles over several months. Individuals with untreated follicular lymphoma might be suitable candidates for this study. The trial includes various health screenings, such as blood tests and scans, to monitor the disease and treatment effects. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that you cannot continue on any medications that are excluded, so it's best to discuss your current medications with the trial team.

Is there any evidence suggesting that copanlisib and rituximab are likely to be safe for humans?

Research shows that the combination of copanlisib and rituximab has been studied for safety. In a previous study, common side effects included high blood sugar (57.8% of patients), high blood pressure (44.1%), nausea (42.6%), and a decrease in certain white blood cells (neutrophils). While the treatment helps slow cancer, it may also cause these effects.

Copanlisib has been safely used with rituximab in other studies, demonstrating that many patients can tolerate it. These treatments specifically target cancer cells, aiming to slow their growth. Participants in similar trials often report these side effects, but the treatment is generally considered manageable.

Anyone considering joining a trial should discuss potential side effects with a healthcare provider. This discussion will help clarify how these effects might impact daily life. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for follicular lymphoma?

Researchers are excited about Copanlisib combined with Rituximab for treating follicular lymphoma because it offers a novel approach by targeting specific pathways involved in cancer cell survival. Unlike standard chemotherapy, Copanlisib is a PI3K inhibitor, which means it blocks signals that cancer cells need to grow. This targeted action could potentially lead to fewer side effects and improved outcomes. Additionally, the combination with Rituximab, a well-known antibody therapy, may enhance the overall effectiveness against lymphoma. This unique treatment pairing harnesses the strengths of both drugs, providing hope for more effective and safer treatment options for patients.

What evidence suggests that copanlisib plus rituximab could be an effective treatment for follicular lymphoma?

In this trial, participants will receive a combination of copanlisib and rituximab to treat follicular lymphoma (FL). Research has shown that using copanlisib and rituximab together can help treat FL. A recent study found that this combination effectively slowed the growth of a type of non-Hodgkin lymphoma similar to FL. Copanlisib blocks certain proteins that cancer cells need to grow, while rituximab helps destroy abnormal B-cells involved in FL. Together, these drugs aim to attack and reduce cancer cells more effectively. Although this combination has shown promise in similar conditions, more research is needed specifically for untreated FL. ^{1 4 6 7 8}

Who Is on the Research Team?

Mark J Roschewski, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

This trial is for people with untreated Follicular Lymphoma (FL) who need systemic therapy due to symptoms or disease progression. Participants must be at least 8 years old, have good organ function, and not have had previous FL treatments except radiation. They should also agree to use effective contraception.

Inclusion Criteria

My organ functions are within normal ranges according to recent tests.

I can take care of myself and am up and about more than half of the day.

I have FL and haven't had chemo, targeted therapy, or antibody treatment before copanlisib, but may have had radiation over 12 weeks ago.

Exclusion Criteria

My lymphoma has spread to my brain or spinal cord.

My diabetes is not under control despite taking my medication.

I have not had a stroke or mini-stroke in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Window Treatment

Participants receive copanlisib monotherapy for a single 28-day cycle

4 weeks

3 visits (in-person)

Induction Therapy

Participants receive copanlisib and rituximab for up to 6 cycles

24 weeks

Weekly visits during the first cycle, then monthly

Extended Induction Therapy

Participants with partial response receive an additional 6 cycles of copanlisib and rituximab

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Annual visits, with additional visits every few months for some participants

What Are the Treatments Tested in This Trial?

Interventions

• Copanlisib
• Rituximab

Trial Overview The study tests the effectiveness of copanlisib plus rituximab in slowing FL growth. It involves up to 13 cycles of treatment over 28 days each, with both drugs administered through IV infusions at varying intervals.

How Is the Trial Designed?

Group I: 1 Experimental Treatment 2 Interventions

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.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study involving 1030 patients with previously untreated follicular lymphoma, the combination of rituximab and lenalidomide showed similar efficacy to rituximab plus chemotherapy, with complete response rates of 48% and 53% respectively at 120 weeks.

The safety profiles differed between the two treatments, with rituximab-chemotherapy leading to higher rates of severe neutropenia, while rituximab-lenalidomide was associated with more severe skin reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab plus Lenalidomide in Advanced Untreated Follicular Lymphoma. Morschhauser, F., Fowler, NH., Feugier, P., et al.[2021]

Rituximab is a highly effective monoclonal antibody for treating various B-cell lymphomas, including follicular lymphoma and diffuse large B-cell lymphoma, demonstrating a strong activity with low toxicity.

The combination of rituximab with chemotherapy (R-CHOP) has shown the highest efficacy reported for any chemotherapy regimen in treating diffuse large B-cell lymphoma and follicular lymphoma, although some patients may still be resistant to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab therapy in malignant lymphoma. Coiffier, B.[2022]

Rituximab is highly effective for treating low-grade CD20+ lymphoma, especially when combined with chemotherapy, which is the standard treatment for follicular lymphoma (FL).

The efficacy of rituximab can be enhanced by combining it with biological agents like interferon-alpha-2a, bortezomib, or lenalidomide, but more research is needed to determine the best combinations and timing of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biological therapy doublets: pairing rituximab with interferon, lenalidomide, and other biological agents in patients with follicular lymphoma. Kimby, E.[2021]

In a review of 49,927 reports from the Spanish Pharmacovigilance System, rituximab was associated with common adverse reactions such as white cell disorders, hypotension, dyspnoea, and pneumonitis, with white cell disorders typically developing around 21 days after treatment.

Trastuzumab was primarily linked to cardiac failure, with many cases occurring alongside other medications, reinforcing the known safety profiles of both drugs as consistent with findings from large clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-marketing safety of antineoplasic monoclonal antibodies: rituximab and trastuzumab. González, V., Salgueiro, E., Jimeno, FJ., et al.[2015]

Rituximab is an effective treatment for follicular lymphoma (FL), improving outcomes when used in combination with traditional chemotherapy, and has shown significant benefits as a maintenance therapy without increasing side effects or compromising patients' quality of life.

Despite its long history of use, new safety alerts and side effects have emerged that clinicians need to be aware of, highlighting the importance of ongoing monitoring and management in patients receiving rituximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Critical appraisal of rituximab in the maintenance treatment of advanced follicular lymphoma. Aguiar-Bujanda, D., Blanco-Sánchez, MJ., Hernández-Sosa, M., et al.[2022]

In a study of 12 patients with relapsing-remitting multiple sclerosis (MS), rituximab was found to be safe and well-tolerated, with no serious adverse reactions reported during an average follow-up of 40 months.

Rituximab treatment resulted in no clinical relapses and improved disability scores in 11 out of 12 patients, indicating its effectiveness for those who had previously failed other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rescue Therapy Using Rituximab for Multiple Sclerosis. Berenguer-Ruiz, L., Sempere, AP., Gimenez-Martinez, J., et al.[2017]

Rituximab is effective in treating both newly diagnosed and relapsed or refractory follicular lymphoma, whether used alone or with chemotherapy.

Due to its good tolerability, rituximab is being explored for maintenance therapy to enhance progression-free and overall survival in patients with follicular lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimization of postremission therapy in follicular lymphoma: efficacy of rituximab maintenance. Roy, R., Gordon, LI.[2019]

Rituximab, when combined with chemotherapy (specifically cyclophosphamide, vincristine, and prednisone), has been approved as a front-line treatment for follicular lymphoma, showing significant benefits in progression-free survival and overall survival based on randomized Phase III studies.

The review highlights that the addition of rituximab to chemotherapy regimens not only improves patient outcomes but also represents a significant advancement in the management of follicular lymphoma over the past three decades.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on front-line therapy for follicular lymphoma: chemo-immunotherapy with rituximab and survival. Turturro, F.[2015]

In a study of 40 patients with low-grade or follicular B-cell non-Hodgkin's lymphoma, the combination of Rituxan (Rituximab) and CHOP chemotherapy resulted in a high overall response rate of 95%, with 55% achieving complete remission.

The combination therapy showed promising safety, with common side effects being manageable, and it also indicated potential for clearing minimal residual disease, as evidenced by the conversion of the bcl-2 translocation from positive to negative in several patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. Czuczman, MS., Grillo-López, AJ., White, CA., et al.[2022]

Rituximab has been shown to be very safe over more than 10 years of use, but it can significantly increase the risk of infections, especially in patients with low-grade lymphoma or severe immunodeficiency, such as those with HIV or on immunosuppressive therapies.

The most critical infection associated with rituximab is hepatitis B reactivation, which can lead to severe liver failure; therefore, screening for hepatitis B and considering preemptive antiviral treatment is essential for patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab-associated infections. Gea-Banacloche, JC.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9011241/

Copanlisib plus rituximab combination therapy vs. ... A recent trial showed copanlisib plus rituximab combination therapy (CRCT) had better efficacy in the treatment of relapsed indolent NHL (iNHL) compared to ...

2. ashpublications.org ashpublications.org/bloodadvances/article/8/18/4866/517175/CHRONOS-4-phase-3-study-of-copanlisib-plus

CHRONOS-4: phase 3 study of copanlisib plus rituximab ... Copanlisib plus R-B did not demonstrate improved PFS or overall survival in patients with relapsed iNHL. Copanlisib plus R-B was associated with more ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02367040

Copanlisib and Rituximab in Relapsed Indolent B-cell Non ... The purpose of this study was to evaluate whether copanlisib in combination with rituximab is superior to placebo in combination with rituximab in prolonging ...

4. cancer.gov cancer.gov/clinicaltrials/NCT03789240

Response-Adapted Therapy With Copanlisib and ... 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 ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2473952924004646

CHRONOS-4: phase 3 study of copanlisib plus rituximab ... Overall, copanlisib plus R-B was associated with higher rates of serious treatment-emergent adverse events (TEAEs), grade 4 and 5 TEAEs, and ...

6. bayer2019tf.q4web.com bayer2019tf.q4web.com/news/news-details/2021/Investigational-Combination-of-Aliqopa-copanlisib-and-rituximab-Significantly-Increases-Progression-Free-Survival-in-Patients-with-Relapsed-Indolent-non-Hodgkins-Lymphoma/default.aspx

Investigational Combination of Aliqopa® (copanlisib) and ... After a median follow-up of 19.2 months, patients treated with this combination had a median PFS of 21.5 months (95% CI 17.9, 33.0) versus 13.8 ...

7. mskcc.org mskcc.org/sites/default/files/node/226579/documents/20210608_hemonc_msk-matasar.pdf

Copanlisib regimen improves outcomes in pretreated ... “Copanlisib is the rst PI3 kinase inhibitor to be safely combined with rituximab in a randomized phase 3 setting, and the rst to demonstrate ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2017/209936Orig1s000Approv.pdf

CENTER FOR DRUG EVALUATION AND RESEARCH PMR 3273-4 In order to characterize the safety of copanlisib from a randomized controlled trial, submit the complete final clinical report and ...