Japanese Phase Ib/II Copanlisib in Relapsed, Indolent B-cell NHL

Open-label, Uncontrolled, Single-arm, Phase Ib/II Study of Intravenous Copanlisib in Japanese Patients With Indolent B-cell Non Hodgkin's Lymphomas Relapsed After or Refractory to Standard Therapy

The primary objective of this study is to assess the safety profile of copanlisib at the recommended dose (primary endpoint). The recommended dose of copanlisib for Japanese patients will be determined in the dose escalation/safety evaluation part.

Study Overview

• Status: Completed
• Conditions: Lymphoma Non-Hodgkin
• Intervention / Treatment: Drug: Copanlisib (BAY80-6946)

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan, 812-8582
  • Fukuoka, Japan, 811-1395
  • Kyoto, Japan, 602-8566
  • Aichi
    • Nagoya, Aichi, Japan, 460-0001
    • Nagoya, Aichi, Japan, 466-8650
    • Nagoya, Aichi, Japan, 466-8560
    • Nagoya, Aichi, Japan, 467-8602
    • Nagoya, Aichi, Japan, 464-8681
  • Gunma
    • Maebashi, Gunma, Japan, 371-8511
  • Hyogo
    • Kobe, Hyogo, Japan, 650-0017
  • Miyagi
    • Sendai, Miyagi, Japan, 980-8574
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
    • Koto-ku, Tokyo, Japan, 135-8550

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 109/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)

• Relapsed or refractory after ≥ 2 prior lines of therapy (refractory defined as not responding to a standard regimen or progressing within 6 months of the last course of a standard regimen). Patients must have previously received rituximab and alkylating agent(s).
• Japanese patients ≥ 20 years of age
• ECOG performance status ≤ 2 (Eastern Cooperative Oncology Group:ECOG)
• Life expectancy of at least 3 months
• Adequate bone marrow, liver and renal function as assessed within 7 days before starting study treatment
• Left ventricular ejection fraction (LVEF) ≥ lower limit of normal (LLN) for the Institution
• Availability of fresh or archival tumor tissue

Exclusion Criteria:

• Uncontrolled hypertension (blood pressure ≥ 150/90 mmHg, defined as systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 90 mmHg, despite optimal medical management)
• Patients with evidence or history of bleeding diathesis. Any hemorrhage or bleeding event ≥ CTCAE Grade 3 (NCI-CTC version 4.0) within 4 weeks of start of study medication (CTCAE: Common Terminology Criteria for Adverse Events, NCI: National Cancer Institute).
• History or concurrent condition of interstitial lung disease or severely impaired pulmonary function
• Unresolved toxicity higher than CTCAE grade 1 attributed to any prior therapy/procedure excluding alopecia.
• Prior treatment with PI3K inhibitors
• Systemic corticosteroid therapy (ongoing)
• Type I or II diabetes mellitus with HbA1c > 8.5% or fasting plasma glucose > 160 mg/dL at Screening
• Known history of human immunodeficiency virus (HIV) infection.
• Hepatitis B or C requiring treatment
• Cytomegalovirus (CMV) PCR positive at baseline
• Known lymphomatous involvement of the central nervous system

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Copanlisib (BAY80-6946); Dose escalation/safety evaluation cohort and objective tumor response (OR) expansion cohort	Drug: Copanlisib (BAY80-6946); Dosing is weekly for the first 3 weeks (on Days 1, 8, and 15) of a 28-day cycle, followed by a 1-week break (i.e., no infusion on Day 22).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with Adverse Events		Up to 18 months
Intensity of AE	The NCI Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0) will be used to assess the intensity of AE	Up to 18 months
Objective Tumor Response (OR)	OR: Best response rating of complete response or partial response according to the criteria defined in the Revised Response Criteria for Malignant Lymphoma(JClin Oncol.2007 Feb)	Up to 18 Years
Recommended dose determined in the dose escalation/safety evaluation		Up to 18 months

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful Links

• Click here to find information for studies related to Bayer products. To find this study enter the ClinicalTrials.gov identifier (NCT) number or Bayer Study Identifier (ID) in the search field.

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2015
• Primary Completion (Actual): September 14, 2018
• Study Completion (Actual): February 10, 2022

Study Registration Dates

• First Submitted: January 15, 2015
• First Submitted That Met QC Criteria: January 15, 2015
• First Posted (Estimate): January 21, 2015

Study Record Updates

• Last Update Posted (Actual): January 20, 2023
• Last Update Submitted That Met QC Criteria: January 19, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Non Hodgkin's Lymphomas
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma
• Other Study ID Numbers: 17792

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No