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Phase III Copanlisib in Rituximab-refractory iNHL (CHRONOS-2)

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02369016
First Posted: February 23, 2015
Last Update Posted: September 6, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Bayer
  Purpose
Assess the efficacy and safety of copanlisib monotherapy

Condition Intervention Phase
Lymphoma, Non-Hodgkin Drug: Copanlisib (BAY 80-6946) Phase 3

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Overall Tumor Response Rate (ORR) [ Time Frame: After all treated patients complete at least 6 Cycles (one cycle is 28 days) of study treatment ]
    Objective tumor response rate (ORR) is defined as the proportion of patients who have a best response rating up to the dates of data analysis of complete response (CR) or partial response (PR) according to the Lugano Classification, and for patients with WM, a response rating of CR, very good partial response (VGPR), PR, or minor response (MR) according to the Owen criteria.


Secondary Outcome Measures:
  • Duration of response (DOR) [ Time Frame: After all treated patients complete at least 6 cycles of study treatment ]
    Defined as the time (in days) from first observed tumor response (Complete Response, Very Good Partial Response, Partial Response or Minor Response) until PD (Progressive disease) or death from any cause, whichever is earlier.

  • Complete response rate (CRR) [ Time Frame: After all treated patients complete at least 6 cycles of study treatment ]
    Defined as patients who have a best response up to the dates of analysis of complete response (CR) according to the Lugano Classification, and for patients with WM, a response rating of CR according to the Owen criteria.

  • Overall survival (OS) [ Time Frame: Up to 3 years after the last patient started study treatment ]
    Defined as the time (in days) from randomization until death from any cause. OS of patients alive at the time of analysis will be censored at the last date they were known to be alive.


Enrollment: 25
Actual Study Start Date: September 22, 2015
Estimated Study Completion Date: May 7, 2018
Estimated Primary Completion Date: May 7, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Copanlisib (BAY 80-6946)
60 mg of experimental drug in solution administered intravenously on Days 1, 8 and 15 of each 28-day treatment cycle
Drug: Copanlisib (BAY 80-6946)
60 mg of experimental drug in solution administered intravenously on Days 1, 8 and 15 of each 28-day treatment cycle

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02369016


  Show 126 Study Locations
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT02369016     History of Changes
Other Study ID Numbers: 17322
2014-000925-19 ( EudraCT Number )
First Submitted: February 17, 2015
First Posted: February 23, 2015
Last Update Posted: September 6, 2017
Last Verified: September 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Bayer:
indolent Non-Hodgkin lymphoma
rituximab-refractory

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents