Copanlisib With Rituximab-Bendamustine in Patients With Relapsed-Refractory Diffuse Large B-cell Lymphoma

NCT04433182 | Terminated Phase 2 DMC

• 1 other identifier: FIL_Copa-RB
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 17

Brief Summary

This is a multicentric single arm phase II trial, to investigate the efficacy (in terms of PFS) of the combination regimen rituximab-bendamustine in association with copanlisib in patients affected by relapsed/refractory DLBCL, not eligible to HDC and ASCT or relapsed after intensified regimens.

Conditions

Diffuse Large B-cell Lymphoma

Keywords

Diffuse Large B-cell Lymphoma; Relapsed-Refractory; DLBCL; Copanlisib

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  Progression-Free Survival (PFS) will be defined as the time between the date of enrolment and the date of disease progression, relapse or death from any cause. Responding patients according to Response Criteria for NHL with PET and patients who are lost to follow-up will be censored at their last assessment date.

  4 years

Secondary Outcomes (6)

• Overall Survival (OS)

  4 years

• Overall Response Rate (ORR)

  End of treament (EOT), 30 months

• Complete Response Rate (CRR)

  End of induction (EOI), 18 months

• Duration of response (DOR)

  4 years

• Conversion rate from SD/PR to PR/CR with maintenance

  End of treatment (after maintenance), 30 months

Study Arms (1)

Single arm Copa-RB

EXPERIMENTAL

Induction phase with Copanlisib, Rituximab and Bendamustina. Maintenance phase (for patients who reach at least SD after induction) with Copanlisib in monotherapy.

Drug: Copanlisib

Interventions

Copanlisib DRUG

Induction phase: 6 cycles of Copa-RB every 28 days according to the following schedule * Copanlisib (Copa): 60 mg/day i.v. on days 1,8,15 * Rituximab (R): 375 mg/sqm i.v. day 1\* * Bendamustine (B): 90 mg/sqm i.v. days 1-2\* note: during cycle 1 rituximab can be administered on day 2: in this case bendamustine will be administered on days 2-3; in the case of a frail patient or a patient with high tumor burden copanlisib could be administered on day 1, rituximab on day 2 and bendamustine on days 3-4, at physician discretion. Maintenance phase: patients who reach at least SD after induction will receive a maintenance with copanlisib in monotherapy according to the following schedule: • Copanlisib: 60 mg/day i.v. on days 1 and 15 in 28-day cycles for 1 year

Also known as: ALIQOPA

Single arm Copa-RB

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed diagnosis of DLBCL (de-novo DLBCL or DLBCL transformed by indolent lymphoma) including:
• DLBCL, NOS including GCB type, ABC type;
• T-cell rich large B-cell Lymphoma;
• Epstein-Barr virus-positive DLBCL, NOS;
• High-grade B-cell Lymphoma with MYC and BCL2 and/or BCL6 rearrangements (double- hit or triple-hit lymphoma);
• High-grade B-cell lymphoma NOS;
• Intravascular B-cell Lymphoma;
• Extranodal DLBCL;
• DLBCL coexistent with either follicular lymphoma of any grade or marginal-zone lymphoma;
• FL grade 3b. Patients must be CD20 positive. New biopsy at relapse time is recommended, but not mandatory.
• Patients must have relapsed (recurrence after complete response or presented progression after partial response) or refractory after at least ≥ 1 (but \< 4) prior lines of therapy, including rituximab-based immunochemotherapy.
• A previous regimen is defined as one of the following: at least 2 months of single-agent therapy; at least 2 consecutive cycles of polychemotherapy; autologous transplant; radioimmunotherapy.
• Patients must not be eligible to high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) or relapsed after that.
• Patients must not be eligible to CAR T-cell therapy or relapsed after that.
• Patients must have at least one bi-dimensionally measurable lesion (that has not been previously irradiated) according to the 2014 Lugano criteria.

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).
• Excluded medical conditions:
• Primary mediastinal B-cell Lymphoma (PMBCL)
• DLBCL with concomitant HHV8 positivity or chronic inflammation
• ALK positive DLBCL
• Known lymphomatous involvement of the central nervous system
• 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
• Uncontrolled arterial hypertension despite optimal medical management
• HbA1c\> 8.5%
• 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. Patients with venous thrombotic events related to lymphoma vascular infiltration or compressive disease are eligible providing no signs of pulmonary embolism
• Non-healing wound, ulcer, or bone fracture

Sponsors & Collaborators

• Fondazione Italiana Linfomi - ETS: lead

Study Sites (17)

Ospedale Monsignor Raffaele Dimiccoli - Ematologia

Barletta, Barletta-Andria-Trani, Italy

Location

Centro Riferimento Oncologico - S.O.C. Oncologia Medica A

Aviano, Pordenone, Italy

Location

Ematologia, Candiolo Cancer Institute. FPO-IRCCS

Candiolo, Torino, 10060, Italy

Location

AOU Ospedali Riuniti - Clinica di Ematologia

Ancona, Italy

Location

ASST Spedali Civili - Ematologia

Brescia, Italy

Location

Arnas Nuovo Ospedale Garibaldi Nesima - U.O.C. Ematologia

Catania, Italy

Location

A.O. S. Croce e Carle - S.C. di Ematologia e Trapianto di Midollo Osseo

Cuneo, Italy

Location

Ospedale Vito Fazzi - Ematologia

Lecce, Italy

Location

Azienda Ospedali Riuniti Papardo-Piemonte - S.C. Ematologia

Messina, Italy

Location

I.R.C.C.S. Istituto Oncologico Veneto - Oncologia 1

Padua, Italy

Location

AOU Policlinico Giaccone - Ematologia

Palermo, Italy

Location

Ospedale Guglielmo da Saliceto - U.O.Ematologia

Piacenza, Italy

Location

Azienda Ospedaliera Sant'Andrea - Ematologia

Roma, Italy

Location

Policlinico Umberto I - Università "La Sapienza" Istituto Ematologia -Dipartimento di Medicina Traslazionale e di Precisione

Roma, Italy

Location

Azienda Ospedaliera S. Maria di Terni - S.C. Oncoematologia

Terni, Italy

Location

Azienda Ospedaliero Universitaria Città della Salute e della Scienza - S.C.Ematologia

Torino, Italy

Location

Ospedale Ca' Foncello - S.C di Ematologia

Treviso, Italy

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

copanlisib

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

• Umberto Vitolo

  Ematologia, Candiolo Cancer Institute. FPO-IRCCS

  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: June 9, 2020
• First Posted: June 16, 2020
• Study Start: August 18, 2020
• Primary Completion: December 19, 2024
• Study Completion: December 19, 2024
• Last Updated: August 8, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (17)