AzTrials
AzTrials

Follicular LymphomaPhase 2NCT03789240

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

A Phase 2 study testing Rituximab, Copanlisib and Bone Marrow Aspiration/Biopsy in people with Follicular Lymphoma and Non-Hodgkin's Lymphoma, run by National Cancer Institute (NCI) at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Follicular Lymphoma, Non-Hodgkin's Lymphoma, NHL
What is being tested?
Rituximab, Copanlisib and Bone Marrow Aspiration/Biopsy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
33 participants
Where
1 siteUnited States
Study dates
22 Aug 2019to 1 Jan 2027
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 24Show fewer
  • 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)
  • Platelets: >=75,000 / mcL (unless due to involvement by lymphoma; transfusions not permitted)
  • Hemoglobin: >= 8 g/dL (transfusions permitted)
  • Renal function: Glomerular filtration rate (GFR) >= 40 mL/min/1.73 m^2 as estimated by the Modification of Diet in Renal Disease (MDRD) abbreviated formula. If not on target, a 24-hour urine creatinine clearance can be used to directly measure.
  • Serum total bilirubin: less than or equal to 1.5 X upper limit of normal (ULN) OR (< 3 x ULN for patients with Gilbert syndrome, patients with cholestasis due to compressive adenopathies of the hepatic hilum or documented liver involvement or with biliary obstruction due to lymphoma)
  • Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) serum glutamic-pyruvic transaminase (SGPT): less than or equal to 2.5 x ULN (less than or equal to 5 x ULN for patients with liver involvement by lymphoma)
  • Lipase: less than or equal to 1.5 x ULN
  • Women of childbearing potential (WOCBP) and men must agree to use effective contraception when sexually active. This applies for the time period between signing of the informed consent form and for at least 1 month after the last dose of copanlisib and
  • 12 months after the last dose of rituximab, whichever is later, for WOCBP and for men after the last administration of study treatment. NOTE: A woman is considered of childbearing potential, (i.e., fertile), following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include but are not limited to hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for continuous 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. The investigator or a designated associate is requested to advise the patient how to achieve highly effective birth control (failure rate of less than 1%), e.g., intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner and sexual abstinence. The use of condoms by male patients is required unless the female partner is permanently sterile.
  • Ability of patient to understand and the willingness to sign a written informed consent document

Who cannot join

  • 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:
Show all 22Show fewer
  • 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
  • Any second malignancy that requires active systemic therapy
  • Known mental or physical illness that would interfere with cooperation with the requirements of the trial or confound the results or interpretation of the results of the trial and, in the opinion of the treating investigator, would make the patient inappropriate for entry into the study.
  • Severe hepatic impairment (Child-Pugh C)
  • Requirement to continue on any of the medications that are excluded
  • Organ compromise that, in the opinion of the principal investigator (PI), necessitates immediate cytoreductive therapy
  • Pregnant or breast-feeding patients. Women of childbearing potential must have a serum pregnancy test performed a maximum of 7 days before start of treatment, and a negative result must be documented before start of treatment
  • Major surgical procedure or significant traumatic injury (as judged by the investigator) within 28 days before start of treatment, or have not recovered from major side effects, open biopsy within 7 days before start of treatment

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: A Phase 2 Study of Response-Adapted Therapy With Copanlisib and Rituximab in Untreated Follicular Lymphoma

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.

Read more

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.

Read the detailed description

Background:

  • Follicular lymphoma (FL) is the most common indolent non-Hodgkins lymphoma (NHL) with a highly variable clinical course across patients
  • Standard frontline therapy for FL includes a monoclonal anti-cluster of differentiation 20 (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 Food and Drug Administration (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 deoxyribonucleic acid (DNA) 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
  • Eastern Cooperative Oncology Group (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
Being tested
Rituximab, Copanlisib, Bone Marrow Aspiration/Biopsy, CT Scans, 18F-FDG-PET/CT Scan15
Keywords
BAY 80-6946, PI3K Target, Aliqopa, Monoclonal Antibody
Medical subject headings
Lymphoma, Follicular, Lymphoma, Non-Hodgkin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RituximabBiological

    Also called Rituxan

    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.

  • CopanlisibDrug

    Also called Aliqopa

    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)

  • Bone Marrow Aspiration/BiopsyProcedure or surgery

    Also called BM Aspiration/Bx

    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.

  • CT ScansDiagnostic test

    Also called Computed tomography scans

    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.

  • 18F-FDG-PET/CT Scan15Diagnostic test

    Also called Fludeoxyglucose F18 (FDG) positron emission tomography /Computed tomography Scan 15

    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.

  • ElectrocardigramDiagnostic test

    Also called ECG

    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.

Study groups in NCT03789240
Study groupRoleWhat they receive
Response-Adapted Therapy With Copanlisib and Rituximab in Untreated Follicular LymphomaExperimentalWindow 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.
Receives: Biological: Rituximab; Drug: Copanlisib; Procedure: Bone Marrow Aspiration/Biopsy; Diagnostic Test: CT Scans; Diagnostic Test: 18F-FDG-PET/CT Scan15; Diagnostic Test: Electrocardigram

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (8)

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

    The proportion of participants with adverse events leading to discontinuation of induction therapy with copanlisib and rituximab.

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

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

    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 positron emission tomography (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. CR30 refers to the proportion of participants who remain in complete response at 30 months from study enrollment. 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.

    Measured: Through 30 months from study enrollment

  3. 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

    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. Under the Lugano criteria (2014), a Complete Response is defined by a Deauville score of 1-3 on positron emission tomography (PET) and no evidence of disease in the bone marrow, with or without a residual mass. Minimal residual disease was defined as detection of circulating tumor deoxyribonucleic acid (DNA) after completion of induction therapy in blood.

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

  4. 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

    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. Partial response was defined using the 2014 Lugano classification for lymphoma and defined as a decrease in the sum of the product of the diameters (SPD) of up to six of the largest nodes or nodal masses.

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

  5. Duration of Response (DOR)

    DOR is defined as time from first documentation of tumor response to disease progression. Progression was defined as evidence of disease growth, recurrence, or new disease based on imaging (computed tomography (CT) or positron-emission tomography (PET/CT) and clinical evaluation.

    Measured: 6 years

  6. Time to Next Treatment (TTNT)

    TTNT is the time from the end of induction therapy with copanlisib and rituximab until initiation of next treatment. Induction therapy is combination therapy with copanlisib and rituximab, and next treatment is start of any systemic therapy after completion of induction therapy with copanlisib and rituximab.

    Measured: time from the end of induction therapy with copanlisib and rituximab until initiation of next treatment, up to 6 years

  7. Progression Free Survival (PFS)

    PFS is the time from study enrollment until disease progression or death from any cause. Disease progression was defined as evidence of disease growth, recurrence, or new disease based on imaging (computed tomography (CT) or positron-emission tomography (PET/CT) and clinical evaluation.

    Measured: time from study enrollment until disease progression or death from any cause, up to 6 years

  8. Overall Survival (OS)

    OS is the time from study enrollment until death from any cause.

    Measured: time from study enrollment until death from any cause, up to 6 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Dec 2018
  2. Study start22 Aug 2019
  3. Primary completion24 Sep 2025
  4. Study completion1 Jan 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
33 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03789240
Sponsor's protocol ID
190030
Other IDs
19-C-0030
Status last verified
Feb 2026
First submitted
18 Dec 2018
Last updated
3 Mar 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. All large-scale genomic sequencing data will be shared with subscribers to the database of Genotypes and Phenotypes (dbGaP).

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Rituximab, Copanlisib and Bone Marrow Aspiration/Biopsy in people with Follicular Lymphoma and Non-Hodgkin's Lymphoma, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 3 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Mar 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of Participants Who Achieve Positron Emission Tomography (PET) - Negative Complete Response (time frame: Within 2 months of induction therapy completion, up to 13 months since start of therapy). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03789240.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Mar 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in