Clinical Trials List
Protocol NumberBAY 80-6946 / 17067
NCT Number(ClinicalTrials.gov Identfier)NCT02367040
2017-05-16 - 2022-07-26
Phase III
Terminated5
ICD-10C85
Other specified and unspecified types of non-Hodgkin lymphoma
A Phase III, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Copanlisib in Combination With Rituximab in Patients With Relapsed Indolent B-cell Non-Hodgkin's Lymphoma (iNHL) - CHRONOS-3
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Trial Applicant
BAYER TAIWAN COMPANY LTD.
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Sponsor
Bayer
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 王全正 無
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Shang-Ju Wu 無
- MING YAO 無
- 劉高郎 無
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Condition/Disease
Relapsed Indolent B-cell Non-Hodgkin's Lymphoma (iNHL)
Objectives
The primary objective of this study is:
! To evaluate whether copanlisib in combination with rituximab is superior to
placebo in combination with rituximab in prolonging progression free survival
(PFS) in patients with relapsed iNHL who have received one or more lines of
treatment, including rituximab and alkylating agents, and who either had a
treatment-free interval of ≥12 months after completion of the last rituximabcontaining treatment, or for whom chemotherapy is contraindicated on reason of
age, comorbidities, and/or residual toxicity (changed by amendment 1)
The secondary objectives of this study are to evaluate: (changed by amendment 1)
! The following characteristics of disease-related symptoms: “time to
deterioration” and “time to improvement”
! Other radiological and clinical indicators of treatment efficacy
! Safety and tolerability of copanlisib
The other objectives of this study are to evaluate:
! Pharmacokinetics
! Biomarkers
! Quality of life
Test Drug
BAY 80-6946 (copanlisib)；phosphatidylinositol 3-kinase (PI3K) inhibitor
Active Ingredient
Copanlisib
Dosage Form
IVT
Dosage
60 mg
Endpoints
Primary Outcome Measures :
Progression free survival (PFS) [ Time Frame: 59 months ]
Progression free survival is defined as the time (in days) from randomization to Disease Progression or death from any cause (if no progression documented).
Secondary Outcome Measures :
Objective tumor response [ Time Frame: 59 months ]
Proportion of responders with best response either complete or partial response.
Duration of response (DOR) [ Time Frame: 59 months ]
Duration of response will only be defined for patients with at least one Complete Response or Partial Response. Patients without disease progression or death at the time of analysis will be censored at the date of their last tumor evaluation.
Complete response [ Time Frame: 59 months ]
Assessed in all patients up to the time of analysis of Progression-free survival.
Time to progression (TTP) [ Time Frame: 59 months ]
The time from randomization to Disease progression or death related to Disease Progression.
Overall survival (OS) [ Time Frame: 59 months ]
The time (in days) from randomization until death from any cause.
Time to deterioration in DRS-P of at least 3 points as measured by the FLymSI-18 (Lymphoma Symptom Index -18)questionnaire [ Time Frame: 59 months ]
Number of participants with adverse Events as a measure of safety and tolerability [ Time Frame: 59 months ]
Time to improvement in DRS-P of at least 3 points, as measured by the FLymSI-18 questionnaire, will be evaluated for patients with a baseline DRS-P score of 30 points or less [ Time Frame: 59 months ]
Progression free survival (PFS) [ Time Frame: 59 months ]
Progression free survival is defined as the time (in days) from randomization to Disease Progression or death from any cause (if no progression documented).
Secondary Outcome Measures :
Objective tumor response [ Time Frame: 59 months ]
Proportion of responders with best response either complete or partial response.
Duration of response (DOR) [ Time Frame: 59 months ]
Duration of response will only be defined for patients with at least one Complete Response or Partial Response. Patients without disease progression or death at the time of analysis will be censored at the date of their last tumor evaluation.
Complete response [ Time Frame: 59 months ]
Assessed in all patients up to the time of analysis of Progression-free survival.
Time to progression (TTP) [ Time Frame: 59 months ]
The time from randomization to Disease progression or death related to Disease Progression.
Overall survival (OS) [ Time Frame: 59 months ]
The time (in days) from randomization until death from any cause.
Time to deterioration in DRS-P of at least 3 points as measured by the FLymSI-18 (Lymphoma Symptom Index -18)questionnaire [ Time Frame: 59 months ]
Number of participants with adverse Events as a measure of safety and tolerability [ Time Frame: 59 months ]
Time to improvement in DRS-P of at least 3 points, as measured by the FLymSI-18 questionnaire, will be evaluated for patients with a baseline DRS-P score of 30 points or less [ Time Frame: 59 months ]
Inclution Criteria
Histologically confirmed diagnosis of CD20 positive iNHL with histological subtype
limited to:
! Follicular lymphoma (FL) G1-2-3a
! Small lymphocytic lymphoma (SLL) with absolute lymphocyte count <5x109
/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 relapsed after at least 1 prior line of therapy, including rituximab
and alkylating agents. A previous regimen is defined as one of the following: at least
2 months of single-agent therapy; at least 2 consecutive cycles of polychemotherapy;
autologous transplant; radioimmunotherapy. Previous exposure to PI3K is acceptable
provided there is no resistance (changed by amendment 1).
Non-WM patients must have at least one bi-dimensionally measurable lesion (that
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 ≥
2x upper limit of normal (changed by amendment 1)
Male or female patients ≥ 18 years of age
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
Life expectancy of at least 3 months
Availability of fresh tumor tissue and/or archival tumor tissue at Screening
Adequate baseline laboratory values as assessed within 7 days before starting study
treatment (changed by amendment 1)
Left ventricular ejection fraction ≥ 45% (changed by amendment 1)
Patients must either
! have had a treatment-free interval of ≥12 months after completion of the last
rituximab-containing treatment
OR
! be considered unfit to receive chemotherapy on reason of age, concomitant
morbidities, and/or residual toxicity from previous treatments. Patients in whom
chemotherapy is contraindicated are defined by one of the following features:
o Age ≥ 80 years
o Age < 80 years and at least 1 of the following conditions:
ß At least 3 grade 3 CIRS-G comorbidities
OR
ß at least 1 grade 4 CIRS-G comorbidity (if considered compatible with
participation in the study) (criterion added by amendment 1)
limited to:
! Follicular lymphoma (FL) G1-2-3a
! Small lymphocytic lymphoma (SLL) with absolute lymphocyte count <5x109
/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 relapsed after at least 1 prior line of therapy, including rituximab
and alkylating agents. A previous regimen is defined as one of the following: at least
2 months of single-agent therapy; at least 2 consecutive cycles of polychemotherapy;
autologous transplant; radioimmunotherapy. Previous exposure to PI3K is acceptable
provided there is no resistance (changed by amendment 1).
Non-WM patients must have at least one bi-dimensionally measurable lesion (that
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 ≥
2x upper limit of normal (changed by amendment 1)
Male or female patients ≥ 18 years of age
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
Life expectancy of at least 3 months
Availability of fresh tumor tissue and/or archival tumor tissue at Screening
Adequate baseline laboratory values as assessed within 7 days before starting study
treatment (changed by amendment 1)
Left ventricular ejection fraction ≥ 45% (changed by amendment 1)
Patients must either
! have had a treatment-free interval of ≥12 months after completion of the last
rituximab-containing treatment
OR
! be considered unfit to receive chemotherapy on reason of age, concomitant
morbidities, and/or residual toxicity from previous treatments. Patients in whom
chemotherapy is contraindicated are defined by one of the following features:
o Age ≥ 80 years
o Age < 80 years and at least 1 of the following conditions:
ß At least 3 grade 3 CIRS-G comorbidities
OR
ß at least 1 grade 4 CIRS-G comorbidity (if considered compatible with
participation in the study) (criterion added by amendment 1)
Exclusion Criteria
Histologically confirmed diagnosis of follicular lymphoma grade 3b or transformed
disease, or chronic lymphocytic leukemia. In patients with clinical suspicion of
transformed disease, a fresh biopsy is recommended.
Last rituximab infusion within 12 months of the start of the next treatment. For
patients considered unfit to receive chemotherapy on reason of age, concomitant
morbidities, and/or residual toxicity from previous treatments: rituximab infusion
within 6 months following the last rituximab-containing regimen (changed by
amendment 1)
History or concurrent condition of interstitial lung disease and/or severely impaired
lung function
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 anti-HCV
antibody will be eligible if they are negative for HCV-RNA (changed by amendment
1). Removed by amendment 1: prior treatment with PI3K inhibitors
disease, or chronic lymphocytic leukemia. In patients with clinical suspicion of
transformed disease, a fresh biopsy is recommended.
Last rituximab infusion within 12 months of the start of the next treatment. For
patients considered unfit to receive chemotherapy on reason of age, concomitant
morbidities, and/or residual toxicity from previous treatments: rituximab infusion
within 6 months following the last rituximab-containing regimen (changed by
amendment 1)
History or concurrent condition of interstitial lung disease and/or severely impaired
lung function
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 anti-HCV
antibody will be eligible if they are negative for HCV-RNA (changed by amendment
1). Removed by amendment 1: prior treatment with PI3K inhibitors
The Estimated Number of Participants
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Taiwan
21 participants
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Global
643 participants
