Study of Copanlisib in Combination With Standard Immunochemotherapy in Rela... | Recruiting
Study of Copanlisib in Combination ... | Recruiting
Study of Copanlisib in Combination With Standard Immunochemotherapy in Relapsed Indolent Non-Hodgkin's Lymphoma (iNHL)
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Medical Conditions
  • Lymphoma, Non-Hodgkin
Primary Contact Details
Bayer Clinical Trials Contact
(+)1-888-84 22937
See all trial contact details
Recruitment Status
Recruiting
Trial source and source ID number
NCT02626455
This information is designed to help you decide whether this trial is of interest. In some cases it is provided as a link to more detailed patient information or it may still be awaited from the organisation running the trial. Please look again shortly if the information you need is not here or, if named, contact the researcher named above.
Summary
The purpose of this study is to assess whether copanlisib in combination with standard immunochemotherapy (rituximab in combination with bendamustine [R-B] and rituximab in combination with a 4 drug combination of cyclophosphamide, doxorubicin, vincristine and prednisone/prednisolone [R-CHOP]) is effective and safe, compared with placebo in combination with standard immunochemotherapy (R-B or R-CHOP) in patients with relapsed iNHL who have received at least one, but at most three, lines of treatment, including rituximab-based immunochemotherapy and alkylating agents.
Research Details
  • Patients should be in need of and fit for immunochemotherapy and should not be resistant to rituximab (resistance defined as lack of response, or progression within 6 months of the last course of treatment with a rituximab containing regimen). This study will be composed of two parts: Safety run-in and phase III part.

    The purpose of the safety run-in part of this study is to assess whether the drug being tested (copanlisib) in combination with standard immunochemotherapy (R-B or R-CHOP) is safe and at what dose level of the study drug (copanlisib - 45mg or 60 mg) patients are able to tolerate the study treatment combination. In addition to finding a safe and tolerable dose level for the phase III part of the study, efficacy will also be evaluated for patients that stay on the study treatment during the safety run-in. The phase III part of the study will start when the recommended dose of copanlisib in combination with R-CHOP and R-B has been defined and confirmed by sponsor, principal investigator and Data Monitoring Committee.

    A maximum of 24 patients will take part in the safety run-in part of this study. In the phase III part approximately 520 patients will be randomly assigned to blinded treatment arms of copanlisib plus R-B or R-CHOP or placebo plus R-B or R-CHOP.
Phase
Phase 3
Study Design
Sorry, this information is not available
Study Type
Interventional
Intervention
Drug : Copanlisib (BAY 80-6946), Drug : Placebo, Drug : Rituximab, Drug : Cyclophosphamide, Drug : Doxorubicin, Drug : Vincristine, Drug : Bendamustine, Drug : Prednisone

Study Arm Groups : Copanlisib + R-B or R-CHOP / Arm 1, Placebo + R-B or R-CHOP / Arm 2, Copanlisib + R-B or R-CHOP / Arm 1, Placebo + R-B or R-CHOP / Arm 2, Copanlisib + R-B or R-CHOP / Arm 1, Placebo + R-B or R-CHOP / Arm 2, Copanlisib + R-B or R-CHOP / Arm 1, Placebo + R-B or R-CHOP / Arm 2, Copanlisib + R-B or R-CHOP / Arm 1, Placebo + R-B or R-CHOP / Arm 2, Copanlisib + R-B or R-CHOP / Arm 1, Placebo + R-B or R-CHOP / Arm 2, Copanlisib + R-B or R-CHOP / Arm 1, Placebo + R-B or R-CHOP / Arm 2

Intervention Type
See Interventions above
Primary Outcome Measures
    Evaluation whether copanlisib in combination with standard immunochemotherapy, is superior to placebo and standard immunochemotherapy assessed by the prolongation of progression free survival (PFS) - applicable to Phase III part; at 53 month; Determination of the recommended Phase III dose (RP3D) of copanlisib in combination with standard immunochemotherapy assessed by the occurrence of dose-limiting toxicity s (DLTs) / adverse events (AEs) - applicable to safety run-in part; at Cycle 1: 21 days or 28 days
Secondary Outcome Measures
    Objective tumor response rate (ORR); at 53 months; Duration of tumor response (DOR); at 53 months; Complete tumor response rate (CRR); at 53 months; Time to tumor progression (TTP); at 53 months; Overall survival (OS); at 53 months; Time to deterioration in disease-related physical symptoms (DRS-P) of at least 3 points as measured by by the FLymSI-18 (Lymphoma Symptom Index -18) questionnaire; at 53 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; at 53 months; Time to next anti-lymphoma treatment (TTNT); at 53 months; Radiological and clinical indicators of treatment efficacy: Progression free survival (PFS); After Cycle 1: day 22 or 29 up to 12 months; Radiological and clinical indicators of treatment efficacy:Objective tumor response rate (ORR); After Cycle 1: day 22 or 29 up to 12 months; Radiological and clinical indicators of treatment efficacy:Duration of tumor response (DOR); After Cycle 1: day 22 or 29 up to 12 months; Radiological and clinical indicators of treatment efficacy: Complete tumor response rate (CRR); After Cycle 1: day 22 or 29 up to 12 months; Radiological and clinical indicators of treatment efficacy: Time to tumor progression (TTP); After Cycle 1: day 22 or 29 up to 12 months; Radiological and clinical indicators of treatment efficacy: Time to next anti-lymphoma treatment (TTNT); After Cycle 1: day 22 or 29 up to 12 months; Radiological and clinical indicators of treatment efficacy: Overall survival (OS); After Cycle 1: day 22 or 29 up to 12 months; Number of participants with adverse events as a measure of safety and tolerability; at 53 months; Radiological and clinical indicators of treatment efficacy: "time to deterioration" in disease-related symptoms - physical (DRS-P) will be assessed using the NCCN-FACT Lymphoma Symptom Index-18 (FLymSI-18) questionnaire; After Cycle 1: day 22 or 29 up to 12 months; Radiological and clinical indicators of treatment efficacy: Time to improvement" in disease-related symptoms - physical (DRS-P) will be assessed using the FLymSI-18 questionnaire; After Cycle 1: day 22 or 29 up to 12 months
Publication(s)
Sorry, this information is not available
Result Reports
Check availability of results on the Clinicaltrials.gov website
This information is designed to help you decide whether this trial is of interest. In some cases it is provided as a link to more detailed patient information or it may still be awaited from the organisation running the trial. Please look again shortly if the information you need is not here or, if named, contact the researcher named above.
Gender
All
Age Range
18 Years - N/A
Who Can Participate
Patients
Number of Participants
546
Participant Inclusion Criteria
    Inclusion Criteria:

    - Histologically confirmed diagnosis of CD20 positive iNHL with histological subtype limited to:

    - Follicular lymphoma G1-2-3a

    - Small lymphocytic lymphoma with absolute lymphocyte count <5x10E9/L at study entry

    - Lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia (LPL/WM)

    - Marginal zone lymphoma (splenic, nodal, or extranodal)

    - Patients must have relapsed after at least 1 but at most 3 prior lines of therapy, including rituximab-based immunochemotherapy 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 cyclesof polychemotherapy; autologous transplant; radioimmunotherapy. Previous exposure to other PI3Ki is acceptable provided there is no resistance.

    - Non-WM must have at least one bi-dimensionally measurable lesion (that has not been previously irradiated) according to 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.

    - 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 collected within 7 days of starting the study treatment

    - Left ventricular ejection fraction (LVEF) ≥ 50%

    Exclusion Criteria

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

    - Rituximab resistance at any line of therapy (resistance defined as lack of response, or progression within 6 months of the last course of treatment with a rituximab containing regimen including rituximab maintenance)

    - History or concurrent condition of interstitial lung disease and/or severely impaired lung function (as judged by the investigator)

    - Known lymphomatous involvement of the central nervous system

    - HbA1c > 8.5% at Screening

    - Known history of human immunodeficiency virus (HIV) infection

    - Hepatitis B (HBV) or hepatitis C (HCV) infection. Patients positive for Hepatitis B surface antigen (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.

    - Cytomegalovirus (CMV) infection. Patients who are CMV PCR positive at baseline will not be eligible.

    - Uncontrolled hypertension despite optimal medical management (per investigator´s assessment)

    - Congestive heart failure > New York Heart Association (NYHA) class 2
Participant Exclusion Criteria
This is in the inclusion criteria above
This information is designed to help you decide whether this trial is of interest. In some cases it is provided as a link to more detailed patient information or it may still be awaited from the organisation running the trial. Please look again shortly if the information you need is not here or, if named, contact the researcher named above.
Trial Location(s)
Royal Marsden - Surrey
Sutton
England
SM2 5PT
South West Wales Cancer Institute
Sketty
Wales
SA2 8QA
Musculoskeletal Department; Freeman Hospital
Newcastle upon Tyne
NE7 7DN
Truro
TR1 3LJ
Royal Marsden Hospital - Sutton
London
England
SW3 6JJ
St George's Hospital
London
SW17 OQT
Harrow
HA1 3UJ
Dorset County Hospital
Dorchester
England
DT1 2JY
Novartis Investigative Site
Exeter
EX2 5AX
Trial Contact(s)
Primary Trial Contact
Bayer Clinical Trials Contact
(+)1-888-84 22937
Other Trial Contacts
Sorry, this information is not available
Countries Recruiting
Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Czechia, Denmark, Finland, France, Germany, Greece, Hong Kong, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Mexico, Poland, Portugal, Romania, Russian Federation, Singapore, Slovakia, South Africa, Spain, Switzerland, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States, Vietnam
This information is designed to help you decide whether this trial is of interest. In some cases it is provided as a link to more detailed patient information or it may still be awaited from the organisation running the trial. Please look again shortly if the information you need is not here or, if named, contact the researcher named above.
Scientific Title
A Phase III, Randomized, Double-blind, Controlled Multicenter Study of Intravenous PI3K Inhibitor Copanlisib in Combination With Standard Immunochemotherapy Versus Standard Immunochemotherapy in Patients With Relapsed Indolent Non-Hodgkin's Lymphoma (iNHL)
EudraCT Number
Not available for this trial
Funder(s)
    Sorry, this information is not available
Other Study ID Numbers
17833
Sponsor(s)
Bayer
Key Dates

Recruitment Start Date

Jan 2016

Recruitment End Date

Sep 2021

Trial Start Date
Date Not Available
Trial End Date
Date Not Available
Date added to source

03 Nov 2015

Date updated in source

12 Apr 2018