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

• ClinicalTrials.gov Identifier: NCT02369016
• Recruitment Status: Active, not recruiting
• First Posted: February 23, 2015
• Last Update Posted: May 28, 2020
• Sponsor: Bayer
• Information provided by (Responsible Party): Bayer

Study Description

Brief Summary:

To assess the safety of copanlisib

Condition or disease	Intervention/treatment	Phase
Lymphoma, Non-Hodgkin	Drug: Copanlisib (BAY 80-6946)	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind Phase III Study of Copanlisib Versus Placebo in Patients With Rituximab-refractory Indolent Non-Hodgkin's Lymphoma (iNHL) - CHRONOS-2
• Actual Study Start Date: September 22, 2015
• Estimated Primary Completion Date: November 30, 2020
• Estimated Study Completion Date: November 30, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Number of patients with treatment-emergent adverse events [ Time Frame: Up to 3 years ]
2. Number of patients with serious adverse events [ Time Frame: Up to 3 years ]
3. Number of patients with abnormal lab parameters [ Time Frame: Up to 3 years ]
4. Number of patients with abnormal vital signs [ Time Frame: Up to 3 years ]

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Brazil

Jaú, Sao Paulo, Brazil, 17210-120

São Paulo, Sao Paulo, Brazil, 08270-070

Sao Paulo, Brazil

Bulgaria

Plovdiv, Bulgaria, 4002

China, Heilongjiang

Harbin, Heilongjiang, China

Greece

Athens, Greece, 11526

Italy

Bologna, Emilia-Romagna, Italy, 40138

Genova, Liguria, Italy, 16132

Korea, Republic of

Jeollabuk-do, Korea, Republic of, 561-712

Jeollanam-do, Korea, Republic of, 519-763

Seoul, Korea, Republic of, 03080

Seoul, Korea, Republic of, 03722

Seoul, Korea, Republic of, 05505

Poland

Gdynia, Poland, 81-519

Portugal

Almada, Portugal, 2801-951

Russian Federation

Kazan, Russian Federation, 420029

Kemerovo, Russian Federation, 650066

Moscow, Russian Federation, 123182

Omsk, Russian Federation, 644013

Penza, Russian Federation, 440071

South Africa

Johannesburg, Gauteng, South Africa, 2013

Taiwan

Taipei, Taiwan, 10002

Turkey

Istanbul, Turkey, 34093

Sponsors and Collaborators

Bayer

Investigators

• Study Director: Bayer Study Director; Bayer

More Information

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT02369016
• Other Study ID Numbers: 17322; 2014-000925-19 ( EudraCT Number )
• First Posted: February 23, 2015
• Last Update Posted: May 28, 2020
• Last Verified: May 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided
• Plan Description: Availability of this study's data will 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.clinicalstudydatarequest.com 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 Study sponsors section of the portal.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Bayer:

indolent Non-Hodgkin lymphoma; rituximab-refractory

Additional relevant MeSH terms:

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