Clinical trial NCT02369016: Phase III Copanlisib in Rituximab-refractory iNHL
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lymphoma, Non-Hodgkin
Keywords: indolent Non-Hodgkin lymphoma
rituximab-refractory
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2015-02-23
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To assess the safety of copanlisib.


Eligibility 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

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAE)s
timeFrame: up to 7 years
measure: Number of Participants With Treatment-emergent Serious Adverse Events (TESAE)s
timeFrame: up to 7 years
measure: Number of Participants With Abnormal Laboratory Parameters
timeFrame: up to 7 years
measure: Number of Participants With Abnormal Vital Signs
timeFrame: up to 7 years
Secondary outcomes:
Other outcomes:
Locations:
city: Jaú
country: Brazil
state: Sao Paulo
city: São Paulo
country: Brazil
state: Sao Paulo
city: Sao Paulo
country: Brazil
city: Plovdiv
country: Bulgaria
city: Athens
country: Greece
city: Bologna
country: Italy
state: Emilia-Romagna
city: Genova
country: Italy
state: Liguria
city: Seoul
country: Korea, Republic of
state: Seoul Teugbyeolsi
city: Jeollabuk-do
country: Korea, Republic of
city: Jeollanam-do
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Gdynia
country: Poland
city: Kazan
country: Russian Federation
city: Kemerovo
country: Russian Federation
city: Moscow
country: Russian Federation
city: Omsk
country: Russian Federation
city: Penza
country: Russian Federation
city: Johannesburg
country: South Africa
state: Gauteng
city: Taipei
country: Taiwan
city: Istanbul
country: Turkey
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: