Study of ME-401 in Subjects With Relapsed or Refractory Indolent B-cell Non-Hodgkin's Lymphoma

A Japanese Phase 1 Study of ME-401 in Subjects With Relapsed or Refractory Indolent B-cell Non-Hodgkin's Lymphoma and Roll Over Study for Subjects Who Have Participated in ME-401-004 Study

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of ME-401 in the treatment of Japanese participants with Relapsed or Refractory indolent B-Cell Non-Hodgkin's Lymphoma and to continue administraion of ME-401 to patients with relapsed or refractory B-cell NHL with collecting safety information

Study Overview

• Status: Active, not recruiting
• Conditions: Relapsed or Refractory Indolent B-cell Non-Hodgkin's Lymphoma
• Intervention / Treatment: Drug: ME-401

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Aomori, Japan, 030-8553
    • Aomori Prefectural Central Hospital
  • Fukuoka, Japan, 812-8582
    • Kyushu University Hospital
  • Okayama, Japan, 700-8558
    • Okayama University Hospital
  • Aichi
    • Nagoya, Aichi, Japan, 460-0001
      • National Hospital Organization Nagoya Medical Center
    • Nagoya, Aichi, Japan, 466-8650
      • Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-0814
      • Hokkaido University Hospital
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8677
      • Tokyo Metropolitan Komagome Hospital
    • Chuo-ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital
    • Koto-ku, Tokyo, Japan, 135-8550
      • The Cancer Institute Hospital of Jfcr

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

[Phase 1 study (DLT evaluation)]

• Patients aged 20 years or older at the submission of the written informed consent form
• Patients with relapsed or refractory B-cell NHL
• Patients who have not undergone phosphatidylinositol 3-kinase inhibitor (PI3K) to date.
• Patients who have undergone Bruton's tyrosine kinase (BTK) inhibitors and have had no exacerbation during the use of BTK inhibitors.
• Patients with ECOG PS 0 or 1.

Exclusion Criteria:

[Phase 1 study (DLT evaluation)]

• Patients who underwent any major surgical treatment within 4 weeks prior to the initiation of the investigational product.
• Patients with poorly controlled diseases. The followings are the examples but the diseases will not be limited to those.
• Patients in whom any of HBV antigen/antibody, HCV antibody, HIV antibody or HTLV-1 antibody will be positive at screening test.
• Patients with active interstitial lung disease or a history thereof.
• Patients who have received the investigational products other than ME-401, systemic chemotherapy or radiotherapy within 4 weeks prior to the initiation of ME-401.

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: ME-401; ME-401 administered orally

Drug: ME-401; [Phase 1 study (DLT evaluation)] ME-401 will be administered at 2 dosages as 45 mg (Cohort 1) or 60 mg (Cohort 2), daily oral administration, QD, and the trial will be initiated at Cohort 1, and medical specialists and the Efficacy and Safety Assessment Committee as needed will decide whether the Cohort will be shifted to the next stage based on their assessment of the safety and tolerability. [Roll over study] 60 mg ME-401 will be administrated on intermittent schedule (1 week on and 3 week off in every 4-week cycle)and will continue until the prescribed mediation in ME-401-004 study is completed or discontinuation criteria are met.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with treatment-emergent adverse events (TEAEs)	Up to approximately 1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
[Phase 1 study (DLT evaluation)] Plasma concentration level of ME-401	Up to approximately 2 years
[Phase 1 study (DLT evaluation)] Maximum plasma drug concentration (Cmax)	Up to approximately 2 years
[Phase 1 study (DLT evaluation)] Area under the plasma drug concentration time curve (AUC)	Up to approximately 2 years
[Phase 1 study (DLT evaluation)] Terminal half-life (t1/2)	Up to approximately 2 years
[Phase 1 study (DLT evaluation)] Efficacy of ME-401 as assessed by the objective response rate (ORR)	Up to approximately 2 years
[Phase 1 study (DLT evaluation)] Efficacy of ME-401 will be assessed by the duration of response (DOR)	Up to approximately 2 years
[Phase 1 study (DLT evaluation)] Efficacy of ME-401 will be assessed by the progression-free survival (PFS)	Up to approximately 2 years
[Phase 1 study (DLT evaluation)] Efficacy of ME-401 will be assessed by the time to response (TTR)	Up to approximately 2 years

Collaborators and Investigators

• Sponsor: Kyowa Kirin Co., Ltd.

Publications and helpful links

General Publications

• Goto H, Izutsu K, Ennishi D, Mishima Y, Makita S, Kato K, Hanaya M, Hirano S, Narushima K, Teshima T, Nagai H, Ishizawa K. Zandelisib (ME-401) in Japanese patients with relapsed or refractory indolent non-Hodgkin's lymphoma: an open-label, multicenter, dose-escalation phase 1 study. Int J Hematol. 2022 Dec;116(6):911-921. doi: 10.1007/s12185-022-03450-5. Epub 2022 Sep 15.

Helpful Links

• Goto H, Izutsu K, Ennishi D, et al. Zandelisib (ME-401) in Japanese patients with relapsed or refractory indolent non-Hodgkin's lymphoma: an open-label, multicenter, dose-escalation phase 1 study. Int J Hematol. 2022 Dec;116(6):911-921.

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2019
• Primary Completion (Anticipated): September 30, 2024
• Study Completion (Anticipated): September 30, 2024

Study Registration Dates

• First Submitted: June 5, 2019
• First Submitted That Met QC Criteria: June 12, 2019
• First Posted (Actual): June 13, 2019

Study Record Updates

• Last Update Posted (Actual): April 13, 2023
• Last Update Submitted That Met QC Criteria: April 11, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: ME-401-K01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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