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

NCT04263584 | Unknown Phase 2 DMC

• 1 other identifier: UKM18-0021
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 12

Brief 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 diffuse large B-cell lymphoma (DLBCL)

Conditions

Diffuse Large B Cell Lymphoma

Keywords

Copanlisib

Outcome Measures

Primary Outcomes (1)

• 2-year progression-free survival

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

  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)

• Overall survival

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

• Event-free survival

  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.

• Rate of complete remission

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

• Rate of partial remission

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

• Overall response rate

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

Study Arms (1)

Copanlisib and R-CHOP chemotherapy

EXPERIMENTAL

All 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.

Drug: Copanlisib; Drug: R-CHOP Chemotherapy

Interventions

Copanlisib DRUG

Copanlisib vials 60 mg

Copanlisib and R-CHOP chemotherapy

R-CHOP Chemotherapy DRUG

Immunochemotherapy

Copanlisib and R-CHOP chemotherapy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• years of age
• 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
• INR and PTT ≤ 1.5 x ULN

You may not qualify if:

• 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
• 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 \[tumor invades lamina propria\])

Sponsors & Collaborators

• University Hospital Muenster: lead
• Bayer: collaborator

Study Sites (12)

University Hospital RWTH Aachen

Aachen, 52074, Germany

Location

Klinikum-Bremen-Mitte

Bremen, 28205, Germany

Location

St.-Johannes-Hospital Dortmund

Dortmund, 44137, Germany

Location

Onkozentrum Dresden

Dresden, 01127, Germany

Location

University Hospital Halle

Halle, 06120, Germany

Location

Westpfalz-Klinikum

Kaiserslautern, 67655, Germany

Location

ÜBAG MVZ Dr. Vehling-Kaiser GmbH

Landshut, 84036, Germany

Location

University Hospital Leipzig

Leipzig, 04103, Germany

Location

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

Munich, 81377, Germany

Location

University Hospital Muenster

Münster, 48149, Germany

Location

Hospital Stuttgart - Stuttgart Cancer Center

Stuttgart, 70174, Germany

Location

University Hospital Ulm

Ulm, 89081, Germany

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

copanlisib; R-CHOP protocol

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Prof. Georg Lenz, MD

  University Hospital Muenster

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2020
• First Posted: February 11, 2020
• Study Start: June 19, 2020
• Primary Completion: April 1, 2025
• Study Completion: April 1, 2025
• Last Updated: January 5, 2024

Record last verified: 2024-01

Locations

DE (12)