Study of Copanlisib in Combination With Standard Immunochemotherapy in Relapsed Indolent Non-Hodgkin's Lymphoma (iNHL)

Official Title

A Phase III, Randomized, Double-blind, Controlled Multicentre Study of Intravenous PI3K Inhibitor Copanlisib in Combination With Standard Immunochemotherapy Versus Standard Immunochemotherapy in Patients With Relapsed Indolent Non-Hodgkin's Lymphoma (iNHL)

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 and alkylating agents.

Trial Description

Primary Outcome:

  • 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
  • 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
Secondary Outcome:
  • Objective tumour response rate (ORR)
  • Duration of tumour response (DOR)
  • Complete tumour response rate (CRR)
  • Time to tumour progression (TTP)
  • Overall survival (OS)
  • 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
  • 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 to next anti-lymphoma treatment (TTNT)
  • Radiological and clinical indicators of treatment efficacy: Progression free survival (PFS)
  • Radiological and clinical indicators of treatment efficacy:Objective tumour response rate (ORR)
  • Radiological and clinical indicators of treatment efficacy:Duration of tumour response (DOR)
  • Radiological and clinical indicators of treatment efficacy: Complete tumour response rate (CRR)
  • Radiological and clinical indicators of treatment efficacy: Time to tumour progression (TTP)
  • Radiological and clinical indicators of treatment efficacy: Time to next anti-lymphoma treatment (TTNT)
  • Radiological and clinical indicators of treatment efficacy: Overall survival (OS)
  • Number of participants with adverse events as a measure of safety and tolerability
  • 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
  • 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
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 676 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.

View this trial on ClinicalTrials.gov

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Resources

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