Phase III Copanlisib in Rituximab-refractory iNHL

• Register: ClinicalTrials.gov
• Last refreshed on: 27 November 2023
• Main ID: NCT02369016
• Date of registration: 17/02/2015
• Prospective Registration: Yes
• Primary sponsor: Bayer
• Public title: Phase III Copanlisib in Rituximab-refractory iNHL CHRONOS-2
• Scientific 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
• Date of first enrolment: September 22, 2015
• Target sample size: 25
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT02369016
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Argentina, Austria, Belarus, Brazil, Bulgaria, Chile, China, Colombia, France, Greece, Hong Kong, Ireland, Italy, Korea, Republic of, Lithuania, Mexico, New Zealand, Poland, Portugal, Russian Federation, Saudi Arabia, Singapore, South Africa, Taiwan, Thailand, Turkey, Ukraine, United States

Contacts

• Name: Bayer Study Director
• Affiliation: Bayer

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Lymphoma, Non-Hodgkin

Intervention(s)

Drug: Copanlisib (BAY 80-6946)

Primary Outcome(s)

Number of Participants With Treatment-emergent Adverse Events (TEAE)s [Time Frame: up to 7 years]

Number of Participants With Abnormal Laboratory Parameters [Time Frame: up to 7 years]

Number of Participants With Abnormal Vital Signs [Time Frame: up to 7 years]

Number of Participants With Treatment-emergent Serious Adverse Events (TESAE)s [Time Frame: up to 7 years]

Secondary ID(s)

17322

2014-000925-19

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 18/11/2023
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02369016