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Diffuse Large B Cell LymphomaPhase 2COPA-R-CHOPNCT04263584

Copanlisib in Combination With Rituximab and CHOP Chemotherapy in Patients With Previously Untreated DLBCL

A Phase 2 study testing Copanlisib and R-CHOP Chemotherapy in people with Diffuse Large B Cell Lymphoma, run by University Hospital Muenster at 16 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a prospective, multicenter, non-randomized, open-label, phase II study to describe the efficacy of R-CHOP plus copanlisib including a safety run-in phase in order to detect early and common unexpected toxicities caused by the addition of copanlisib to the standard immuno-chemotherapy R-CHOP in patients with… Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Diffuse Large B Cell Lymphoma
What is being tested?
Copanlisib and R-CHOP Chemotherapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
62 participants
Where
16 sitesGermany
Study dates
19 Jun 2020to 3 May 2025
Phase
Phase 2
Are there results?
None posted in the registry

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 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed
  • DLBCL (NOS) or
  • High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements or
  • High-grade B-cell lymphoma (NOS)
  • Follicular lymphoma Grade 3B (primary diagnosis without history of indolent lymphoma) with a diagnostic biopsy performed within 3 months before study entry and with material available for central review and complimentary scientific analyses
  • 18-80 years of age
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  • International Prognostic Index (IPI) 2-5
  • Eastern Cooperative Oncology Group Performance status (ECOG) 0-2
  • Life expectancy of at least 3 months
  • Women of childbearing potential 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 6 months after the last administration of study treatment. 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, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner and sexual abstinence. The use of condoms by male patients is required unless the female partner is permanently sterile.
  • Adequate baseline laboratory values collected no more than 7 days before starting study treatment:
  • Total bilirubin ≤ 1.5 x ULN (< 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)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver involvement by lymphoma)
  • Lipase ≤ 1.5 x ULN
  • Glomerular filtration rate (GFR) ≥ 40 mL/min/1.73 m2 according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. If not on target, this evaluation may be repeated once after at least 24 hours either according to the CKD-EPI formula or by 24-hour sampling. If the later result is within acceptable range, it may be used to fulfill the inclusion criteria instead.
  • INR and PTT ≤ 1.5 x ULN
  • Platelet count ≥ 75,000 /mm3.
  • Hemoglobin (Hb) ≥ 8 g/dL
  • Absolute neutrophil count (ANC) ≥ 1,500/mm3
  • Left ventricular ejection fraction ≥ 50%
  • No prior lymphoma therapy
  • Ability to understand and willingness to sign written informed consent. Signed informed consent must be obtained before any study specific procedure.

Who cannot join

  • Patients who meet any of the following criteria at the time of screening will be excluded.
  • Previous assignment to treatment during this study. Patients permanently withdrawn from study participation will not be allowed to re-enter the study.
  • Previous (within 28 days or less than 5 half-lives of the drug before start of study treatment) or concomitant participation in another clinical study with investigational medicinal product(s).
  • Close affiliation with the investigational site; e.g. a close relative of the investigator, dependent persons (e.g. employee or student of the investigational site).
  • Excluded medical conditions:
  • Type I or II diabetes mellitus with HbA1c > 8.5% at screening or fasting plasma glucose > 160 mg/dL at screening
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  • History or concurrent condition of interstitial lung disease and/or severely impaired lung function (as judged by the investigator)
  • Known lymphoma involvement of the central nervous system
  • Human immunodeficiency virus (HIV) infection
  • Hepatitis B (HBV) and C (HCV) infection. Patients with serologic markers of HBV immunization due to vaccination (HBsAg negative, Anti-HBc negative and Anti-HBs positive) will be eligible
  • CMV-PCR positive at baseline
  • Previous or concurrent history of malignancies within 5 years prior to study treatment except for curatively treated:
  • Cervical carcinoma in situ
  • Non-melanoma skin cancer
  • Superficial bladder cancer (Ta [non-invasive tumor], Tis [carcinoma in situ] and T1 [tumor invades lamina propria])
  • Localized prostate cancer
  • Patients with evidence or history of bleeding diathesis. Any hemorrhage or bleeding event ≥ CTCAE Grade 3 within 4 weeks prior to the start of study medication
  • Patients with seizure disorder requiring medication
  • Proteinuria of ≥ CTCAE Grade 3 as assessed by a 24h protein quantification or estimated by urine protein: creatinine ratio > 3.5 on a random urine sample
  • Concurrent diagnosis of pheochromocytoma
  • Congestive heart failure > New York Heart Association (NYHA) class 2
  • Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months)
  • Myocardial infarction less than 6 months before start of test drug
  • Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 3 months before the start of study medication
  • Non-healing wound, ulcer, or bone fracture
  • Active, clinically serious infections > CTCAE Grade 2
  • Uncontrolled hypertension (systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg despite optimal medical management)
  • Known history of drug induced liver injury, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, on-going extra-hepatic obstruction caused by cholelithiasis, cirrhosis of the liver or portal hypertension
  • Ongoing inflammatory bowel disease
  • History of, or current autoimmune disease
  • Prior treatment with PI3K inhibitors
  • Any other co-existing medical or psychological condition that will preclude participation in the study or compromise ability to give informed consent
  • Patient is pregnant (β-HCG positive) or breast-feeding
  • Known hypersensitivity to copanlisib or to any of the excipients of rituximab, cyclophosphamide, doxorubicine, vincristine, and/or prednisone

Trial locations and contacts

16 sites in 1 country.

16 sites in 1 country

Germany16 sites

  • University Hospital RWTH Aachen

    Aachen, 52074

  • Haematology and Oncology Practice

    Augsburg, 86150

  • Klinikum-Bremen-Mitte

    Bremen, 28205

  • St.-Johannes-Hospital Dortmund

    Dortmund, 44137

  • Onkozentrum Dresden

    Dresden, 01127

  • University Hospital Halle

    Halle, 06120

  • University Medical Center Hamburg-Eppendorf

    Hamburg, 20246

  • Westpfalz-Klinikum

    Kaiserslautern, 67655

  • Karlsruhe City Hospital

    Karlsruhe, 76133

  • ÜBAG MVZ Dr. Vehling-Kaiser GmbH

    Landshut, 84036

  • University Hospital Leipzig

    Leipzig, 04103

  • Ludwigshafen City Hospital

    Ludwigshafen, 67063

  • Hospital of the Ludwig-Maximilians-University (LMU) Munich

    Munich, 81377

  • University Hospital Muenster

    Münster, 48149

  • Hospital Stuttgart - Stuttgart Cancer Center

    Stuttgart, 70174

  • University Hospital Ulm

    Ulm, 89081

Other trials in Germany

About this study

Official title: A Prospective Multicenter Phase 2 Study of Copanlisib in Combination With Rituximab and CHOP Chemotherapy (COPA-R-CHOP) in Patients With Previously Untreated Diffuse Large B-cell Lymphoma (DLBCL)

This is a prospective, multicenter, non-randomized, open-label, phase II study to describe the efficacy of R-CHOP plus copanlisib including a safety run-in phase in order to detect early and common unexpected toxicities caused by the addition of copanlisib to the standard immuno-chemotherapy R-CHOP in patients with diffuse large B-cell lymphoma (DLBCL)

Read the detailed description

Patients diagnosed with DLBCL can be cured with a combined approach of CHOP chemotherapy and the anti-CD20 antibody rituximab in roughly 65% of cases. About one third of patients with DLBCL relapse or show primary progressive disease after modern first-line therapy. The outcome of these patients is poor in particular if first-line therapy contained rituximab. Novel therapeutic approaches are urgently warranted. Thus, it is the goal to further improve progression-free Survival (PFS) and overall Survival (OS) by combining R-CHOP with copanlisib. Copanlisib is a small molecule pan-class 1 PI3K inhibitor and approved by US FDA for the treatment of adult patients with relapsed follicular lymphoma who have received at least two prior systemic therapies.

Being tested
Copanlisib, R-CHOP Chemotherapy
Keywords
Copanlisib
Medical subject headings
Lymphoma, Large B-Cell, Diffuse

What participants receive

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

  • CopanlisibDrug

    Copanlisib vials 60 mg

  • R-CHOP ChemotherapyDrug

    Immunochemotherapy

Study groups in NCT04263584
Study groupRoleWhat they receive
Copanlisib and R-CHOP chemotherapyExperimentalAll patients will receive 6 cycles of R-CHOP immunochemotherapy every two weeks with the following doses per cycle: rituximab 375 mg/m², cyclophosphamide 750 mg/m², doxorubicin 50 mg/ m², vincristine 1.4 mg/m² (dose capped at 2 mg or 1 mg for individuals above 60 years of age), prednisolone 500 mg. In addition, copanlisib at a dose of 60 mg will be administered on days 1 and 8 of each 21-day cycle of R-CHOP in the first 6 patients. If dose limiting toxicity (DLT) occurs in no more than one out of these 6 patients during cycle 1, additional 6 patients at 60 mg will be enrolled and treated for at least 1 cycle before opening the phase II portion of the study. If a DLT is observed in 2 or more of the first 6 patients during cycle 1 the dose of copanlisib will be reduced to 45 mg on days 1 and 8 for the next 6 patients. The data of the safety run-in analysis (first 12 patients) will be presented to the Data Safety Monitoring Board and the recommended phase 2 dose will be determined.
Receives: Drug: Copanlisib; Drug: R-CHOP Chemotherapy

What is being measured

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

  1. 2-year progression-free survival

    Length of time that a patient lives without disease progression or relapse.

    Measured: From the day of inclusion into the study until event (disease progression, relapse, death due to any other cause) occurs, assessed up to 4 years.

Secondary outcomes (14)

  1. Overall survival

    The percentage of patients in this study who are still alive.

    Measured: From the day of inclusion into the study to death due to any cause, assessed up to 4 years.

  2. Event-free survival

    Length of time that a patient remains free of certain events (disease progression, start of additional, unplanned antitumor therapy, relapse, death due to any other cause).

    Measured: From the day of inclusion into the study until event (disease progression, start of additional, unplanned anti-tumor therapy, relapse, death due to any other cause) occurs, assessed up to 4 years.

  3. Rate of complete remission

    Rate of complete remission measured as number of complete remissions divided by the number of patients included.

    Measured: From the day of inclusion into the study until date of complete remission, assessed up to 4 years.

  4. Rate of partial remission

    Rate of partial remission measured as number of partial remissions divided by the number of patients included.

    Measured: From the day of inclusion into the study until date of partial remission, assessed up to 4 years.

  5. Overall response rate

    Overall response rate measured as number of complete and partial remissions divided by the number of patients included.

    Measured: From the day of inclusion into the study until date of complete or partial remission, assessed up to 4 years.

  6. Progression rate

    Progression rate measured as number of progressions divided by the number of patients included.

    Measured: From the day of inclusion into the study until date of progression during therapy or within 2 months after last treatment course.

  7. Relapse rate

    Relapse rate measured as number of relapses divided by the number of patients included.

    Measured: From the day of inclusion into the study until date of relapse during therapy or within 2 months after last treatment course.

  8. Duration of response

    The time between the initial response to therapy and subsequent disease progression or relapse.

    Measured: From documentation of tumor response to relapse, assessed up to 4 years.

  9. Adverse events and serious adverse events

    Frequency of adverse events and serious adverse events

    Measured: The documentation of adverse events, including serious adverse events, starts with first study treatment after patient inclusion and ends 100 days after the last application of copanlisib or any component of R-CHOP

  10. Rate of treatment-related deaths

    The number of deaths during therapy or up to 2 months after the end of therapy divided by the number of patients included.

    Measured: From the start of therapy up to 2 months after the end of therapy.

  11. Therapy cycles (number)

    Number of therapy cycles

    Measured: From the start of therapy (copanlisib and R-CHOP) until the end of therapy (last application of copanlisib or any component of R-CHOP), assessed up to 0.5 years.

  12. Therapy cycles (duration)

    Duration of therapy cycles

    Measured: From the start of therapy (copanlisib and R-CHOP) until the end of therapy (last application of copanlisib or any component of R-CHOP), assessed up to 0.5 years.

  13. Used drugs

    Cumulative doses of R-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone, rituximab) and copanlisib.

    Measured: From the start of therapy (copanlisib and R-CHOP) until the end of therapy (last application of copanlisib or any component of R-CHOP), assessed up to 0.5 years.

  14. Outcome according to lymphoma biology

    Lymphoma tissue from all patients will be characterized.

    Measured: From the start of study until the end of study, assessed up to 4 years.

Timeline

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

  1. First posted11 Feb 2020
  2. Study start19 Jun 2020
  3. Primary completion3 May 2025
  4. Study completion3 May 2025

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
62 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04263584
Sponsor's protocol ID
UKM18-0021
Acronym
COPA-R-CHOP
Status last verified
Jan 2024
First submitted
7 Jan 2020
Last updated
30 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Copanlisib and R-CHOP Chemotherapy in people with Diffuse Large B Cell Lymphoma, run by University Hospital Muenster at 16 sites in Germany.

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 22 inclusion and 34 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: finished, as of the sponsor's last update on 30 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in Germany. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

2-year progression-free survival (time frame: From the day of inclusion into the study until event (disease progression, relapse, death due to any other cause) occurs, assessed up to 4 years.). 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 NCT04263584.

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 30 Jul 2026.

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