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

Bayer

Status and phase

Completed

Phase 3

Conditions

Lymphoma, Non-Hodgkin

Treatments

Drug: Copanlisib (BAY 80-6946)

Study type

Interventional

Funder types

Industry

Identifiers

NCT02369016

17322

2014-000925-19 (EudraCT Number)

Details and patient eligibility

About

To assess the safety of copanlisib.

Enrollment

25 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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