check_circleStudy Completed

Lymphoma, Non-Hodgkin

Phase III copanlisib in rituximab-refractory iNHL

Trial purpose

To assess the safety of copanlisib.

Key Participants Requirements

Sex

All

Age

18 - N/A
  • - 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
  • - 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

Trial summary

Enrollment Goal
25
Trial Dates
September 2015 - October 2022
Phase
Phase 3
Could I Receive a placebo
No
Products
Aliqopa (Copanlisib, BAY80-6946)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Withdrawn
Pretoria, 0044, South Africa
Withdrawn
George, 6530, South Africa
Withdrawn
Saxonwold, 2196, South Africa
Completed
Johannesburg, 2013, South Africa
Withdrawn
Pretoria, 0140, South Africa
Completed
Bologna, 40138, Italy
Withdrawn
Milano, 20089, Italy
Completed
Genova, 16132, Italy
Withdrawn
Firenze, 50141, Italy
Withdrawn
Roma, 00161, Italy
Withdrawn
Linz, 4020, Austria
Withdrawn
Innsbruck, 6020, Austria
Withdrawn
Medellin, 050034, Colombia
Completed
Istanbul, 34093, Turkey
Withdrawn
Canton, 44718, United States
Withdrawn
Santiago, Chile
Withdrawn
Santiago, 8420383, Chile
Withdrawn
St. Petersburg, 197758, Russian Federation
Withdrawn
Krasnoyarsk, 660133, Russian Federation
Completed
Omsk, 644013, Russian Federation
Withdrawn
Orel, 302028, Russian Federation
Completed
Penza, 440071, Russian Federation
Withdrawn
Petrozavodsk, 185019, Russian Federation
Completed
Kemerovo, 650066, Russian Federation
Withdrawn
Volgograd, 400138, Russian Federation
Withdrawn
Arkhangelsk, 163045, Russian Federation
Withdrawn
Whittier, 90602, United States
Withdrawn
Bend, 97701, United States
Withdrawn
Clinton, 2753, United States
Withdrawn
Somerville, 08876, United States
Withdrawn
Khmel'nytsky, Ukraine
Withdrawn
Lviv, 79044, Ukraine
Withdrawn
Watertown, 57201, United States
Completed
Taipei, 100, Taiwan
Completed
Gdynia, 81-519, Poland
Withdrawn
Taipei, 11217, Taiwan
Withdrawn
Córdoba, X5000JHQ, Argentina
Completed
Plovdiv, 4000, Bulgaria
Withdrawn
Resistencia, 3500, Argentina
Withdrawn
Buenos Aires, CP: C1431FWO, Argentina
Withdrawn
Oaxaca, 68000, Mexico
Withdrawn
Hong Kong, NA, Hong Kong
Withdrawn
Shatin, Hong Kong
Withdrawn
Rio de Janeiro, 22793-080, Brazil
Withdrawn
Rankweil, 6830, Austria
Withdrawn
Santiago, 8380456, Chile
Withdrawn
Porto, 4200-072, Portugal
Withdrawn
Porto, 4200- 319, Portugal
Withdrawn
Almada, 2801-951, Portugal
Withdrawn
Vila Nova de Gaia, 4434-502, Portugal
Withdrawn
Sao Paulo, 05651-901, Brazil
Withdrawn
Jeddah, P.O Box 80215-Jeddah, Saudi Arabia
Withdrawn
Makkah, P.O BOX 57657-MAKKAH, Saudi Arabia
Withdrawn
Dammam, P.O Box 15215-Dammam, Saudi Arabia
Withdrawn
Monterrey, 64460, Mexico
Withdrawn
Passo Fundo, 99010-080, Brazil
Withdrawn
Porto Alegre, 90880-480, Brazil
Withdrawn
Dublin, 9, Ireland
Withdrawn
Bangkok, 10400, Thailand
Withdrawn
São Paulo, 01234-030, Brazil
Terminated
Sao Paulo, Brazil
Completed
Jaú, 17210-120, Brazil
Withdrawn
Rochester, 55905, United States
Withdrawn
Ijuí, 98700-000, Brazil
Withdrawn
Seoul, 06351, Korea, Republic Of
Completed
Seoul, 03080, Korea, Republic Of
Completed
Jeollabuk-do, 561-712, Korea, Republic Of
Completed
Seoul, 3722, Korea, Republic Of
Withdrawn
Singapore, 169610, Singapore
Completed
Athens, 115 26, Greece
Withdrawn
Chaidari, 12462, Greece
Withdrawn
Athens, 106 76, Greece
Withdrawn
Piraeus, 18 537, Greece
Withdrawn
Tauranga, 3112, New Zealand
Completed
Moscow, 123182, Russian Federation
Completed
Kazan, 420029, Russian Federation
Withdrawn
México, D. F., 06726, Mexico
Completed
São Paulo, 08270-070, Brazil
Completed
Seoul, 05505, Korea, Republic Of
Completed
Jeollanam-do, 58128, Korea, Republic Of
Withdrawn
Shanghai, 200032, China
Withdrawn
Guangzhou, 510060, China
Withdrawn
Beijing, 100142, China
Withdrawn
Beijing, 100021, China
Withdrawn
Beijing, China
Withdrawn
Shanghai, 200025, China
Withdrawn
Tianjin, 300121, China
Withdrawn
Nanjing, 210009, China
Withdrawn
Denizli, 20070, Turkey
Withdrawn
Hangzhou, 310000, China
Withdrawn
Suzhou, 215006, China
Withdrawn
Minsk, 220013, Belarus
Withdrawn
Lesnoy, 223040, Belarus
Withdrawn
Tainan, 704, Taiwan
Withdrawn
Kaohsiung, 833, Taiwan

Primary Outcome

  • Number of participants with treatment-emergent adverse events (TEAE)s
    Adverse event data were collected after signing the informed consent until 30 days after the last study drug administration (end of safety follow-up)
    date_rangeTime Frame:
    up to 7 years
  • Number of participants with treatment-emergent serious adverse events (TESAE)s
    Serious adverse event data were collected after signing the informed consent until 30 days after the last study drug administration (end of safety follow-up)
    date_rangeTime Frame:
    up to 7 years
  • Number of participants with abnormal laboratory parameters
    - Above threshold of 10% and reported as TEAEs - any event (Grade 1-4)
    date_rangeTime Frame:
    up to 7 years
  • Number of participants with abnormal vital signs
    - Reported as TEAEs - worst CTCAE grade total -
    date_rangeTime Frame:
    up to 7 years

Trial design

A randomized, double-blind Phase III study of copanlisib versus placebo in patients with rituximab-refractory indolent non-Hodgkin’s lymphoma (iNHL) - CHRONOS-2
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
N/A
Blinding
Double Blind
Assignment
Single Group Assignment
Trial Arms
1