Clinical Trials /

Copanlisib and Rituximab in Relapsed Indolent B-cell Non-Hodgkin's Lymphoma (iNHL)

NCT02367040

Description:

The purpose 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 who either had a treatment-free interval of ≥ 12 months after completion of the last rituximab-containing treatment, or who are unwilling to receive chemotherapy/for whom chemotherapy is contraindicated on reason of age, comorbidities, and/or residual toxicity.

Related Conditions:
  • Follicular Lymphoma
  • Lymphoplasmacytic Lymphoma
  • Marginal Zone Lymphoma
  • Small Lymphocytic Lymphoma
  • Waldenstrom Macroglobulinemia
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Copanlisib and Rituximab in Relapsed Indolent B-cell Non-Hodgkin's Lymphoma (iNHL)
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: 17067
  • SECONDARY ID: 2013-003893-29
  • NCT ID: NCT02367040

Conditions

  • Lymphoma,Non-Hodgkin

Interventions

DrugSynonymsArms
Copanlisib (BAY 80-6946)Copanlisib + Rituximab
PlaceboPlacebo + Rituximab
RituximabCopanlisib + Rituximab

Purpose

The purpose 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 who either had a treatment-free interval of ≥ 12 months after completion of the last rituximab-containing treatment, or who are unwilling to receive chemotherapy/for whom chemotherapy is contraindicated on reason of age, comorbidities, and/or residual toxicity.

Trial Arms

NameTypeDescriptionInterventions
Copanlisib + RituximabExperimentalCombination of the Copanlisib and rituximab
  • Copanlisib (BAY 80-6946)
  • Rituximab
Placebo + RituximabPlacebo ComparatorCombination of Copanlisib placebo and rituximab
  • Placebo
  • Rituximab

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed diagnosis of Indolent non-Hodgkin's lymphoma (iNHL) in CD20
             positive patients, with histological subtype limited to:

               -  Follicular lymphoma(FL) grade1-2-3a

               -  Small lymphocytic lymphoma(SLL) with absolute lymphocyte count <5x10*9/L at study
                  entry

               -  Lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia (LPL/WM)

               -  Marginal zone lymphoma (MZL) (splenic, nodal, or extra-nodal)

          -  Patients must have relapsed (recurrence after complete response or presented
             progression after partial response) after the last rituximab-, rituximab biosimilars-,
             or anti-CD20 monoclonal antibody (e.g. obinutuzumab)-containing therapy (other
             previous treatment lines after rituximab are allowed). A previous regimen is defined
             as one of the following: at least 2 months of single-agent therapy (less than 2 months
             of therapy is allowed for patients who responded to single-agent rituximab, rituximab
             biosimilars, or anti-CD20 monoclonal antibody); at least 2 consecutive cycles of
             polychemotherapy; autologous transplant; radioimmunotherapy. Previous exposure to PI3K
             is acceptable (except to copanlisib) provided there is no resistance. Patients with
             prior intolerance to PI3K inhibitors other than copanlisib are eligible.

          -  Non-WM must have at least one bi-dimensionally measurable lesion (which has not been
             previously irradiated) according to the Lugano Classification. For patients with
             splenic MZL (Marginal-zone lymphoma) this requirement may be restricted to
             splenomegaly alone since that is usually the only manifestation of measurable disease.

          -  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 .

          -  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 for central
             pathology(obtained within 5 years of the consent date) at Screening

          -  Adequate baseline laboratory values collected no more than 7 days before starting
             study treatment

          -  Left ventricular ejection fraction ≥ 45%

          -  Patients must either:

               -  have had a progression-free and treatment-free interval of at least 12 months
                  after completion of the rituximab-, rituximab biosimilars-, or anti-CD20
                  monoclonal antibody-containing treatment OR

               -  be considered unfit to receive chemotherapy on reason of age, concomitant
                  morbidities, and/or residual toxicity from previous treatments, or unwillingness
                  to receive chemotherapy. These patients must also have had a progression-free and
                  treatment-free interval of at least 6 months after completion of the last
                  rituximab-, rituximab biosimilars-, or anti-CD20 monoclonal antibody-containing
                  treatment. Patients in whom chemotherapy is contraindicated are defined by one of
                  the following features:

                    -  Age ≥ 80 years

                    -  Age < 80 years and at least 1 of the following conditions:

                         -  at least 3 grade 3 CIRS-G comorbidities OR

                         -  at least 1 grade 4 CIRS-G comorbidity (if compatible to participation
                            in the study).

        Exclusion Criteria:

          -  Histologically confirmed diagnosis of follicular lymphoma grade 3b or transformed
             disease, or chronic lymphocytic leukemia

          -  Progression free interval or treatment free interval of less than 12 months since the
             last rituximab-, rituximab biosimilars-, or anti-CD20 monoclonal antibody (e.g.

        obinutuzumab)-containing treatment(including maintenance with these drugs). For patients
        considered unwilling/unfit to receive chemotherapy : progression free interval or treatment
        free interval of less than 6 months since the last rituximab-, rituximab biosimilars-, or
        anti-CD20 monoclonal antibody-containing treatment (including maintenance with these
        drugs), as assessed by the investigator

          -  History or concurrent condition of interstitial lung disease of any severity and/or
             severely impaired lung function

          -  Known lymphomatous involvement of the central nervous system

          -  Patients with HbA1c > 8.5% 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, these patients should receive prophylactic
             antiviral therapy. Patients positive for anti- HCV antibody will be eligible if they
             are negative for HCV-RNA

          -  Documented evidence of resistance to prior treatment with idelalisib or other PI3K
             inhibitors.

          -  Prior treatment with copanlisib

          -  Cytomegalovirus (CMV) infection. Patients who are CMV PCR positive at baseline will
             not be eligible
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression free survival (PFS)
Time Frame:59 months
Safety Issue:
Description: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

Measure:Objective tumor response
Time Frame:59 months
Safety Issue:
Description:Proportion of responders with best response either complete or partial response.
Measure:Duration of response (DOR)
Time Frame:59 months
Safety Issue:
Description: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.
Measure:Complete response
Time Frame:59 months
Safety Issue:
Description:Assessed in all patients up to the time of analysis of Progression-free survival.
Measure:Time to progression (TTP)
Time Frame:59 months
Safety Issue:
Description:The time from randomization to Disease progression or death related to Disease Progression.
Measure:Overall survival (OS)
Time Frame:59 months
Safety Issue:
Description:The time (in days) from randomization until death from any cause.
Measure: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
Safety Issue:
Description:
Measure:Number of participants with adverse Events as a measure of safety and tolerability
Time Frame:59 months
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Bayer

Trial Keywords

  • Clinical trial, Phase III
  • Phosphatidylinositol-3-kinase
  • Non-Hodgkin's lymphoma
  • Indolent B-cell non-Hodgkin's lymphoma

Last Updated

December 11, 2019