Phase III Copanlisib in Rituximab-refractory iNHL (CHRONOS-2)

A Randomized, Double-blind Phase III Study of Copanlisib Versus Placebo in Patients With Rituximab-refractory Indolent Non-Hodgkin's Lymphoma (iNHL) - CHRONOS-2

To assess the safety of copanlisib.

Study Overview

• Status: Completed
• Conditions: Lymphoma, Non-Hodgkin
• Intervention / Treatment: Drug: Copanlisib (BAY 80-6946)

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo, Brazil
  • Sao Paulo
    • Jaú, Sao Paulo, Brazil, 17210-120
    • São Paulo, Sao Paulo, Brazil, 08270-070
• Bulgaria
  • Plovdiv, Bulgaria, 4000
• Greece
  • Athens, Greece, 115 26
• Italy
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
  • Liguria
    • Genova, Liguria, Italy, 16132
• Korea, Republic of
  • Jeollabuk-do, Korea, Republic of, 561-712
  • Jeollanam-do, Korea, Republic of, 58128
  • Seoul, Korea, Republic of, 05505
  • Seoul, Korea, Republic of, 3722
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 03080
• Poland
  • Gdynia, Poland, 81-519
• Russian Federation
  • Kazan, Russian Federation, 420029
  • Kemerovo, Russian Federation, 650066
  • Moscow, Russian Federation, 123182
  • Omsk, Russian Federation, 644013
  • Penza, Russian Federation, 440071
• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2013
• Taiwan
  • Taipei, Taiwan, 100
• Turkey
  • Istanbul, Turkey, 34093

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed diagnosis of indolent B-cell NHL, with histological subtype limited to the following:

  • Follicular lymphoma (FL) grade 1-2-3a.
  • Small lymphocytic lymphoma (SLL) with absolute lymphocyte count < 5 x 10*9/L at the time of diagnosis and at study entry.
  • Lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia (LPL/WM).
  • Marginal zone lymphoma (MZL) (splenic, nodal, or extra-nodal).
• Patients must have received two or more prior lines of treatment. A previous regimen is defined as one of the following: at least two months of single-agent therapy, at least two consecutive cycles of polychemotherapy, autologous transplant, radioimmunotherapy.
• Prior therapy must include rituximab and alkylating agents.Prior exposure to idelalisib or other PI3K inhibitors is acceptable (except to copanlisib) provided that there is no resistance.
• Patients must be refractory to the last rituximab-based treatment, defined as no response or response lasting < 6 months after completion of treatment. Time interval to assess refractoriness will be calculated between the end date (last day) of the last rituximab-containing regimen and the day of diagnosis confirmation of the subsequent relapse.
• Patients must have at least one bi-dimensionally measurable lesion (which has not been previously irradiated) according to the Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification.
• Patients affected by WM, who do not have at least one bi-dimensionally measurable lesion in the baseline radiologic assessment, must have measurable disease, defined as presence of immunoglobulin M (IgM) paraprotein with a minimum IgM level ≥ 2 x upper limit of normal (ULN)and positive immunofixation test.
• ECOG performance status ≤ 1
• Adequate bone marrow, liver and renal function

Exclusion Criteria:

• Histologically confirmed diagnosis of FL grade 3b.
• Chronic lymphocytic leukemia (CLL).

• Transformed disease (assessed by investigator):

  • histological confirmation of transformation, or
  • clinical and laboratory signs: rapid disease progression, high standardized uptake value (SUV) (> 12) by positron emission tomography (PET) at baseline if PET scans are performed (optional).
• Bulky disease - Lymph nodes or tumor mass (except spleen) >= 7cm LD (longest diameter)
• Known lymphomatous involvement of the central nervous system.
• Uncontrolled arterial hypertension despite optimal medical management (per investigator's assessment).
• Type I or II diabetes mellitus with HbA1c > 8.5% at Screening.
• Known history of human immunodeficiency virus (HIV) infection.
• Active clinically serious infections > CTCAE Grade 2
• Active Hepatitis B or hepatitis C
• History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function (as judged by the investigator)
• History of having received an allogeneic bone marrow or organ transplant
• Positive cytomegalovirus (CMV) PCR test at baseline
• Pregnant or breast-feeding patients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Copanlisib (BAY 80-6946); patients with rituximab-refractory iNHL	Drug: Copanlisib (BAY 80-6946); 60 mg of experimental drug in solution administered intravenously on Days 1, 8 and 15 of each 28-day treatment cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAE)s	Adverse event data were collected after signing the informed consent until 30 days after the last study drug administration (end of safety follow-up)	up to 7 years
Number of Participants With Treatment-emergent Serious Adverse Events (TESAE)s	Serious adverse event data were collected after signing the informed consent until 30 days after the last study drug administration (end of safety follow-up)	up to 7 years
Number of Participants With Abnormal Laboratory Parameters	- Above threshold of 10% and reported as TEAEs - any event (Grade 1-4)	up to 7 years
Number of Participants With Abnormal Vital Signs	- Reported as TEAEs - worst CTCAE grade total -	up to 7 years

Collaborators and Investigators

• Sponsor: Bayer
• Investigators: Study Director: Bayer Study Director, Bayer

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2015
• Primary Completion (Actual): October 26, 2022
• Study Completion (Actual): October 26, 2022

Study Registration Dates

• First Submitted: February 17, 2015
• First Submitted That Met QC Criteria: February 17, 2015
• First Posted (Estimated): February 23, 2015

Study Record Updates

• Last Update Posted (Estimated): November 16, 2023
• Last Update Submitted That Met QC Criteria: November 15, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: indolent Non-Hodgkin lymphoma; rituximab-refractory
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: 17322; 2014-000925-19 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No