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

NCT03789240 | Active Not Recruiting Phase 2 Results FDA Drug

• 2 other identifiers: 19003019-C-0030
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

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.

Conditions

Follicular Lymphoma; NHL; Non-Hodgkin's Lymphoma

Keywords

BAY 80-6946; PI3K Target; Aliqopa; Monoclonal Antibody

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants Who Achieve Positron Emission Tomography (PET) - Negative Complete Response

  The response rate will be determined and reported along with a 95% confidence interval. Complete Response was assessed by the Lugano Classification of Response Criteria and is defined as the proportion of participants who achieve a PET-negative complete response in accordance with the 2014 Lugano classification of the International Working Group Criteria for Non-Hodgkin's Lymphoma after induction therapy with copanlisib and rituximab. Under the Lugano criteria (2014), a Complete Response is defined by a Deauville score of 1-3 on PET and no evidence of disease in the bone marrow, with or without a residual mass.

  Within 2 months of induction therapy completion, up to 13 months since start of therapy

Secondary Outcomes (8)

• Proportion of Participants With Serious and/or Non-serious Adverse Events Leading to Discontinuation of Induction Therapy With Copanlisib and Rituximab

  Through study induction therapy period and until 1 month after completion of induction

• Proportion of Participants With a Continuous Complete Response Rate at 30 Months (CR30)

  Through 30 months from study enrollment

• Complete Molecular Remission (CMR) Rate Defined as the Proportion of Participants Who Achieve Both a Complete Response and Are Negative on Molecular Assays for Minimal Residual Disease After Induction Therapy With Copanlisib and Rituximab

  Through study induction therapy period and until 1 month after completion of induction

• Objective Response Rate (ORR) Defined as the Proportion of Participants Who Achieve at Least a Partial Response (PR) to Induction Therapy With Copanlisib and Rituximab

  Through study induction therapy period and until 1 month after completion of induction

• Duration of Response (DOR)

  6 years

Other Outcomes (1)

• Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

  Adverse events were monitored/assessed from the first administration of study drug through 30 days post the last administration of study drug.

Study Arms (1)

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

EXPERIMENTAL

Window of treatment with Copanlisib 60mg via intravenous (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/m\^2 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.

Biological: Rituximab; Drug: Copanlisib; Procedure: Bone Marrow Aspiration/Biopsy; Diagnostic Test: CT Scans; Diagnostic Test: 18F-FDG-PET/CT Scan15; Diagnostic Test: Electrocardigram

Interventions

Bone Marrow Aspiration/Biopsy PROCEDURE

Screening. Cycles 6 \& 12, last 7 days of the cycle (disease evaluations). Follow-up (prior to progressive disease) every 3 or 6 months. Bone marrow aspiration with flow cytometry and biopsy (within 12 months prior to starting treatment) if clinically indicated; repeat in follow-up to confirm response or progression.

Also known as: BM Aspiration/Bx

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

CT Scans DIAGNOSTIC_TEST

Screening and Baseline. Copanlisib Window (Cycle 0/ore Cycle 1 Day 1) Day-28 to -1 (-14 scheduling window). Cycles 3 \& 9 and Cycles 6 \& 12, last 7 days of the cycle (disease evaluations). Follow-up (prior to progressive disease) every 3 or 6 months. End of treatment (discontinued/progressive disease). Follow-up (prior to progressive disease) every 3 or 6 months. CT scans (preferred) of chest, abdomen and pelvis at baseline; may be adjusted to assess additional known sites of disease, as needed. Scans performed after cycles 3 and 6 (last 7 days of each cycle) of both induction and maintenance, as applicable. Repeat also within last 7 days of copanlisib window. MRIs may be used instead of CT scans as necessary.

Also known as: Computed tomography scans

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

18F-FDG-PET/CT Scan15 DIAGNOSTIC_TEST

Screening and Baseline. Copanlisib Window (Cycle 0/ore Cycle 1 Day 1) Day-28 to -1 (-14 scheduling window). Cycles 6 \& 12, last 7 days of the cycle (disease evaluations). PET scans to be performed after cycles 6 and 12 (last 7 days of each cycle) of both induction and maintenance, as applicable. Repeat also within last 7 days of copanlisib window.

Also known as: Fludeoxyglucose F18 (FDG) positron emission tomography /Computed tomography Scan 15

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

Electrocardigram DIAGNOSTIC_TEST

Baseline. Copanlisib Window (Cycle 0/ore Cycle 1 Day 1) Day-28 to -1 (-14 scheduling window). Cycles 3 \& 9 and Cycles 6 \& 12, last 7 days of the cycle (disease evaluations). End of treatment (discontinued/progressive disease). Follow-up (prior to progressive disease) every 3 or 6 months. Participants with prolonged QTc at baseline, participants with congenital prolonged QT syndrome, and participants chronically on medications as specified in the protocol will have ECG monitoring after copanlisib window, and every 3 cycles thereafter.

Also known as: ECG

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

Rituximab BIOLOGICAL

Rituximab is administered at a dose of 375 mg/m\^2 via intravenous (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.

Also known as: Rituxan

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

Copanlisib DRUG

Copanlisib is administered at a fixed dose of 60 mg via intravenous (IV) weekly for the first 3 weeks on Days 1, 8, and 15 followed by a 1-week break (no infusion on Day 22)

Also known as: Aliqopa

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a confirmed histologic diagnosis of Follicular Lymphoma (FL), grade 1-2 or 3a, according to the criteria established by the most recent version of the World Health Organization (WHO) classification system. Pathologic diagnosis must be confirmed by Laboratory of Pathology, National Cancer Institute (NCI)
• Stage II-IV disease. NOTE: Patients with stage I FL who have been treated with radiation therapy and have subsequently relapsed are eligible.
• No prior systemic treatment for FL with chemotherapy, targeted small molecule therapy, or monoclonal antibody therapy prior to the first dose of copanlisib treatment. Patients may have received prior radiation therapy only; radiation therapy must have been completed \>12 weeks prior to the first dose of copanlisib. NOTE: Prior shortterm (less than or equal to 7 days) use of corticosteroids for acute medical complications related to sites of FL involvement is permitted.
• Patients must meet standard criteria for initiation of systemic therapy as evidenced by presence of one of the following:
• Development of symptomatic enlarged lymph nodes or spleen
• Development of B symptoms (fever, night sweats, weight loss) or severe pruritus
• Development of significant serous pleural or pericardial effusions (small effusions seen only on computed tomography (CT) scans are not indications for systemic therapy)
• Development of bone marrow failure as a result of involvement by FL and not attributable to other causes; this would be manifest as a hemoglobin (Hgb) \< 9 g/dl, absolute neutrophil count \< 1 x 10\^9/L, or platelet count \< 75 x 10\^9/L
• Critical organ involvement, organ compression (e.g., ureteric obstruction or epidural compression), or significant risk of future organ compressions
• Increase in the size of lymph nodes on CT scans indicating progression of disease from previous CT scans
• Adequate tissue from diagnostic biopsy; formalin fixed tissue block or 20 slides of tumor sample (archival or fresh) must be available for performance of correlative studies
• Be greater than or equal to 8 years of age on day of signing informed consent. NOTE: Because no dosing or adverse event data are currently available on the use of (copanlisib) in patients \<18 years of age, children are excluded from this study
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Adequate organ function as evidenced by the following laboratory parameters:
• Absolute neutrophil count (ANC): \>= 1,500 /mm\^3 (unless due to involvement by lymphoma or benign ethnic neutropenia)

You may not qualify if:

• Known lymphomatous involvement of the central nervous system
• History of any known primary or acquired immunodeficiency syndrome (e.g., human immunodeficiency virus (HIV))
• Cytomegalovirus (CMV) polymerase chain reaction (PCR) positive at baseline
• Hepatitis B surface antigen (HbsAg) or core antibody (HbcAb) positive with a positive Hep B DNA Quantitative, HBV Viral Load result.
• NOTE: Subjects with positive hepatitis B serology (hepatitis B surface antigen (HbsAg) or Hepatitis B core antibody (HBcAb) may be enrolled onto the study but they must have a negative Hep B deoxyribonucleic acid (DNA) Quantitative, hepatitis B virus (HBV) Viral Load result before enrollment.
• Uncontrolled intercurrent illness including, but not limited to the following that may limit interpretation of results or that could increase risk to the patient at the discretion of the investigator:
• Active autoimmune disease that has required systemic treatment in the past 12 months (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• History of (non-infectious) pneumonitis that required steroids, evidence of interstitial lung disease or active, non-infectious pneumonitis.
• Active hepatitis C infection. NOTE: Subjects who are hepatitis C antibody positive will need to have a negative HCV PCR result before enrollment. Those with a positive PCR for hepatitis C are excluded.
• Congestive heart failure \> New York Heart Association (NYHA) class 2
• Unstable angina
• Myocardial infarction in the past 6 months
• Uncontrolled hypertension despite optimal medical management
• Arterial thromboembolic events such as cerebrovascular accident (including transient ischemic attacks), in prior 3 months
• Uncontrolled Type I or II diabetes despite optimal medical management

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Lymphoma, Follicular; Lymphoma, Non-Hodgkin

Interventions

Rituximab; copanlisib; Biopsy; Tomography, X-Ray Computed; Positron-Emission Tomography; Electrocardiography

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Image Interpretation, Computer-Assisted; Diagnostic Imaging; Radiographic Image Enhancement; Image Enhancement; Photography; Radiography; Tomography, X-Ray; Tomography; Tomography, Emission-Computed; Radionuclide Imaging; Diagnostic Techniques, Radioisotope; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Electrodiagnosis

Results Point of Contact

• Title: Rahul Lakhotia, M.B.B.S.
• Organization: National Cancer Institute

rahul.lakhotia@nih.gov

240-858-7242

Study Officials

• Rahul Lakhotia, M.B.B.S.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 18, 2018
• First Posted: December 28, 2018
• Study Start: August 22, 2019
• Primary Completion: September 24, 2025
• Study Completion (Estimated): January 1, 2027
• Last Updated: March 3, 2026
• Results First Posted: March 3, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data will be available during the study and indefinitely. Genomic data will be available once genomic data are uploaded per protocol Genomic Data Sharing (GDS) plan for as long as database is active.
• Access Criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI). Genomic data will be made available via the database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians.

Locations

US (1)