Clinical Trials List
Protocol NumberBAY 80-6946 / 17322
NCT Number(ClinicalTrials.gov Identfier)NCT02369016
2015-05-01 - 2018-12-19
Phase III
Terminated2
ICD-10C85.90
Non-Hodgkin lymphoma, unspecified, unspecified site
A randomized, double-blind Phase III study of copanlisib versus placebo in patients with rituximab-refractory indolent non-Hodgkin’s lymphoma (iNHL) – CHRONOS-2
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Trial Applicant
BAYER TAIWAN COMPANY LTD.
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Sponsor
Bayer
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Jin-Hwang Liu Division of Hematology & Oncology
- Chia-Jen Liu Division of Hematology & Oncology
- Tzeon-jye Chiou Division of Hematology & Oncology
- Chun-Yu Liu Division of Hematology & Oncology
- 洪曼馨 Division of Hematology & Oncology
- Liang-Tsai Hsiao Division of Hematology & Oncology
- 曾成槐 Division of Hematology & Oncology
- Jyh-Pyng Gau Division of Hematology & Oncology
- 李函叡 Division of Radiology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Shang-Ju Wu Division of Hematology & Oncology
- Sheng-chieh Chou Division of Hematology & Oncology
- 劉高郎 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Condition/Disease
indolent non-Hodgkin’s lymphoma (iNHL)
Objectives
To investigate whether copanlisib as monotherapy is superior to
placebo in prolonging progression-free survival (PFS) in patients
with rituximab-refractory iNHL who have received two or more
prior lines of treatment, have been exposed to rituximab and
alkylating agent(s), and have progressed within six months of the
end of the last previous rituximab-containing regimen (changed by
amendment 1).
Test Drug
BAY 80-6946
Active Ingredient
Copanlisib
Dosage Form
Lyophilized Powder for Injection
Dosage
60
Endpoints
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 ]
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 ]
Inclution 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 109
/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 (changed
by amendment 1). 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 agent(s). Prior
exposure to idelalisib or other PI3K inhibitors is acceptable provided that
there is no resistance (modified by amendment 1).
Patients must be refractory to the last rituximab-based treatment (no
response or response lasting < 6 months).
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 (changed by
amendment 1).
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)
(changed by amendment 1).
Male or female patients ≥ 18 years of age.
ECOG (Eastern Cooperative Oncology Group) performance status ≤ 1.
Life expectancy of at least 3 months.
Availability of fresh (preferred) and/or archival tumor tissue at Screening.
Adequate bone marrow, liver and renal function as assessed within 7 day
before start of study treatment.
Left ventricular ejection fraction (LVEF) ≥ the lower limit of normal
(LLN) for the Institution.
histological subtype limited to the following:
! Follicular lymphoma (FL) grade 1-2-3a.
! Small lymphocytic lymphoma (SLL) with absolute lymphocyte
count < 5 x 109
/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 (changed
by amendment 1). 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 agent(s). Prior
exposure to idelalisib or other PI3K inhibitors is acceptable provided that
there is no resistance (modified by amendment 1).
Patients must be refractory to the last rituximab-based treatment (no
response or response lasting < 6 months).
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 (changed by
amendment 1).
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)
(changed by amendment 1).
Male or female patients ≥ 18 years of age.
ECOG (Eastern Cooperative Oncology Group) performance status ≤ 1.
Life expectancy of at least 3 months.
Availability of fresh (preferred) and/or archival tumor tissue at Screening.
Adequate bone marrow, liver and renal function as assessed within 7 day
before start of study treatment.
Left ventricular ejection fraction (LVEF) ≥ the lower limit of normal
(LLN) for the Institution.
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 (> 12) by positron emission tomography
(PET) at baseline if PET scans are performed (optional).
Bulky disease (criterion changed by amendment 1):
! Lymph nodes or tumor mass (except spleen) ≥ 7 cm LDi (longest
diameter).
Known lymphomatous involvement of the central nervous system.
Type I or II diabetes mellitus with HbA1c > 8.5% or fasting plasma
glucose > 160 mg/dL at Screening.
Known history of human immunodeficiency virus (HIV) infection.
Hepatitis B (HBV) or hepatitis C (HCV). Patients positive for HBsAg or
HBcAb will be eligible if they are negative for HBV-DNA. Patients
positive for HCV immunoglobulin G (IgG) will be eligible if they are
negative for HCV-RNA.
History or concurrent condition of interstitial lung disease of any severity
and/or severely impaired lung function (clarified by amendment 1).
Documented evidence of resistance to a prior treatment with idelalisib or
other PI3K inhibitors defined as (exclusion criterion added by
amendment 1):
! No response (response defined as partial response [PR] or complete
response [CR]) at any time during therapy, or
! Progression (PD) after any response (PR/CR) or after stable disease
(SD) within 6 months from the end of the therapy with a PI3K
inhibitor.
Patients who discontinued treatment due to other reason than
disease progression, and did not exhibit any signs of PD, will be
allowed to enroll in this study after discussion with the sponsor.
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 (> 12) by positron emission tomography
(PET) at baseline if PET scans are performed (optional).
Bulky disease (criterion changed by amendment 1):
! Lymph nodes or tumor mass (except spleen) ≥ 7 cm LDi (longest
diameter).
Known lymphomatous involvement of the central nervous system.
Type I or II diabetes mellitus with HbA1c > 8.5% or fasting plasma
glucose > 160 mg/dL at Screening.
Known history of human immunodeficiency virus (HIV) infection.
Hepatitis B (HBV) or hepatitis C (HCV). Patients positive for HBsAg or
HBcAb will be eligible if they are negative for HBV-DNA. Patients
positive for HCV immunoglobulin G (IgG) will be eligible if they are
negative for HCV-RNA.
History or concurrent condition of interstitial lung disease of any severity
and/or severely impaired lung function (clarified by amendment 1).
Documented evidence of resistance to a prior treatment with idelalisib or
other PI3K inhibitors defined as (exclusion criterion added by
amendment 1):
! No response (response defined as partial response [PR] or complete
response [CR]) at any time during therapy, or
! Progression (PD) after any response (PR/CR) or after stable disease
(SD) within 6 months from the end of the therapy with a PI3K
inhibitor.
Patients who discontinued treatment due to other reason than
disease progression, and did not exhibit any signs of PD, will be
allowed to enroll in this study after discussion with the sponsor.
The Estimated Number of Participants
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Taiwan
3 participants
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Global
25 participants
