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

Study Description

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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

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	25 participants
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 7, 2018
Estimated Study Completion Date :	December 19, 2018

Arms and Interventions

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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

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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

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
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

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  Show 26 Study Locations

Sponsors and Collaborators

Bayer

Investigators

Study Director:	Bayer Study Director	Bayer

More Information

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Additional Information:

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Responsible Party:	Bayer
ClinicalTrials.gov Identifier:	NCT02369016 History of Changes
Other Study ID Numbers:	17322; 2014-000925-19 ( EudraCT Number )
First Posted:	February 23, 2015
Last Update Posted:	May 21, 2018
Last Verified:	May 2018

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; Rituximab; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents