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Trial record 1 of 1 for:    NCT02367040
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Copanlisib and Rituximab in Relapsed Indolent B-cell Non-Hodgkin's Lymphoma (iNHL) (CHRONOS-3)

This study is currently recruiting participants.
Verified November 2017 by Bayer
Sponsor:
ClinicalTrials.gov Identifier:
NCT02367040
First Posted: February 20, 2015
Last Update Posted: November 14, 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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Bayer
  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. Purpose of the study is also to evaluate the safety and tolerability of copanlisib.

Approximately 567 patients will be randomly assigned in in blinded treatment arms copanlisib plus rituximab or placebo plus rituximab.

Copanlisib will be administered on Days 1, 8 and 15 of each 28-day cycle. Placebo dosing will be administered on the same days as copanlisib.

Rituximab dose is administered weekly during Cycle 1 on Days 1, 8, 15 and 22, and then on Day 1 of Cycles 3, 5, 7 and 9. The maximum administration of rituximab is 8 times.

Copanlisib or placebo treatment will be continued until disease progression, unacceptable toxicity, or until another criterion is met for withdrawal from the study treatment.

Following the end of treatment visit, patients will enter either the Safety follow-up or the Active follow-up period.

The efficacy is measured by duration of progression-free survival (time between randomization and onset of a further progression of disease, or death from any cause). Progression of disease will be determined by radiologic tumor assessments to be performed at screening, as well as during the active follow up period tumor assessments every 8 weeks during Year 1, every 12 weeks during Year 2, and every 24 weeks during Year 3.

Blood samples will be collected for safety analysis and pharmacokinetic analysis. Archival tumor tissue and blood samples will be collected for biomarker analysis and for central pathology review, fresh biopsy tissue and bone marrow will be collected but not mandatory.


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

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Progression free survival (PFS) [ Time Frame: 59 months ]
    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:
  • Objective tumor response [ Time Frame: 59 months ]
    Proportion of responders with best response either complete or partial response.

  • Duration of response (DOR) [ Time Frame: 59 months ]
    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.

  • Complete response [ Time Frame: 59 months ]
    Assessed in all patients up to the time of analysis of Progression-free survival.

  • Time to progression (TTP) [ Time Frame: 59 months ]
    The time from randomization to Disease progression or death related to Disease Progression.

  • Overall survival (OS) [ Time Frame: 59 months ]
    The time (in days) from randomization until death from any cause.

  • 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 ]
  • Number of participants with adverse Events as a measure of safety and tolerability [ Time Frame: 59 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 [ Time Frame: 59 months ]

Estimated Enrollment: 567
Actual Study Start Date: August 3, 2015
Estimated Study Completion Date: August 28, 2020
Estimated Primary Completion Date: March 31, 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Copanlisib + Rituximab
Combination of the Copanlisib and rituximab
Drug: Copanlisib (BAY 80-6946)
Copanlisib is supplied as lyophilized preparation in a 6 mL injection vial. The total amount of copanlisib per vial is 60 mg. The solution for IV infusions is obtained after reconstitution with normal saline solution. Dosing will be administered on Days 1, 8 and 15 of each 28-day cycle. Copanlisib will be administered before rituximab.
Drug: Rituximab
Rituximab dose 375 mg/m2 body surface weekly during Cycle 1 on Days 1, 8, 15 and 22, and then on Day 1 of Cycles 3, 5, 7 and 9.The solution for IV infusions is obtained after reconstitution of a calculated concentration of 1 to 4 mg/ml rituximab into an infusion bag containing sterile, pyrogen-free sodium chloride 9 mg/ml (0.9%) solution for injection or 5% D-Glucose in water.
Placebo Comparator: Placebo + Rituximab
Combination of Copanlisib placebo and rituximab
Drug: Placebo
Placebo is supplied as lyophilized preparation in a 6 mL injection vial. The developed placebo lyophilisate is equivalent to the 60 mg copanlisib formulation, with regard to the composition of excipients and the instructions for reconstitution and dose preparation. Placebo dosing will be administered on Days 1, 8 and 15 of each 28-day cycle. Placebo will be administered before rituximab.
Drug: Rituximab
Rituximab dose 375 mg/m2 body surface weekly during Cycle 1 on Days 1, 8, 15 and 22, and then on Day 1 of Cycles 3, 5, 7 and 9.The solution for IV infusions is obtained after reconstitution of a calculated concentration of 1 to 4 mg/ml rituximab into an infusion bag containing sterile, pyrogen-free sodium chloride 9 mg/ml (0.9%) solution for injection or 5% D-Glucose in water.

  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 CD20 positive Indolent non-Hodgkin's lymphoma (iNHL) with histological subtype limited to:
  • Follicular lymphoma grade1-2-3a
  • Small lymphocytic lymphoma with absolute lymphocyte count <5x10*9/L at the time of diagnosis and at study entry
  • Lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia (LPL/WM)
  • Marginal zone lymphoma (splenic, nodal, or extra-nodal)
  • Patients must have relapsed (recurrence after complete response or presented progression after partial response) after at least 1 prior line of therapy, including rituximab. A previous regimen is defined as one of the following: at least 2 months of single-agent therapy; at least 2 consecutive cycles of polychemotherapy; autologous transplant; radioimmunotherapy. Previous exposure to PI3K (except to copanlisib) is acceptable 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 (that has not been previously irradiated) according to the Lugano Classification.
  • Patients affected by W M 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 no more than 7 days before starting study treatment
  • Left ventricular ejection fraction ≥ 45%
  • Patients must either have had a treatment-free interval of at least 12 months after completion of the last rituximab-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.

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 containing treatment (including rituximab maintenance). For patients considered unfit to receive chemotherapy : progression free interval or treatment free interval of less than 6 months since the last rituximab containing treatment (including rituximab maintenance), 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
  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): NCT02367040


Contacts
Contact: Bayer Clinical Trials Contact 49 30 300139003 clinical-trials-contact@bayer.com
Contact: For trial location information (Phone Menu Options '3' or '4') (+)1-888-84 22937

  Show 295 Study Locations
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT02367040     History of Changes
Other Study ID Numbers: 17067
2013-003893-29 ( EudraCT Number )
First Submitted: February 12, 2015
First Posted: February 20, 2015
Last Update Posted: November 14, 2017
Last Verified: November 2017

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

Keywords provided by Bayer:
Clinical trial, Phase III
Phosphatidylinositol-3-kinase
Non-Hodgkin's lymphoma
Indolent B-cell non-Hodgkin's lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
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