A Study to Assess Safety and Efficacy of CHO-H01 as a Single Agent/Combined With Lenalidomide in Subjects With Refractory or Relapsed Non-Hodgkin's Lymphoma

Официальное название

A Phase I/IIa, Open-label, Multicenter Study of the Safety and Efficacy of CHO-H01 as a Single Agent/Combined With Lenalidomide to Subjects With Refractory or Relapsed Non-Hodgkin's Lymphoma

Обзор

This is a 2-part study. Part 1/Phase 1 of the study will be conducted to determine the safety and tolerability of CHO-H01 in subjects with relapsed/refractory CD20+ non-Hodgkin's lymphoma. It will also determine maximum tolerated dose (MTD) and recommended phase II dose (RP2D). Part 2/Phase 2a will assess the anticancer activity and safety of CHO-H01 plus lenalidomide in subjects with low-grade relapsed/refractory CD20+ non-Hodgkin's lymphoma.

Подробное описание

Phase I FIH study includes subjects with relapsed/refractory CD20 + non-Hodgkin's lymphoma, who may benefit from treatment with CHO-H01. In Phase I of the study, the first 2 cohorts will follow a 2-step modified accelerated titration dose escalation design and subsequent cohorts will follow a standard 3+3 dose escalation design.

The investigational medicinal product, CHO-H01, will be administered via IV infusion once weekly for 4 weeks in Cycle 1 and then once only (on Day 1) in each subsequent 21-day cycle until disease progression or for up to 6 cycles (19 weeks) of treatment.

Once the MTD/RP2D has been confirmed, Phase IIa of the study will be initiated. The purpose of Phase IIa is to assess anticancer activity and safety of CHO-H01 plus lenalidomide in low-grade relapsed/refractory CD20 + non Hodgkin's lymphoma, including follicular lymphoma (Grades 1-3a), marginal zone lymphoma, and small lymphocytic lymphoma.

Вмешательства

• Препарат CHO-H01
  Phase 1: Subjects will be administered intravenous (IV) infusion of assigned dose level of CHO-H01, once a week for 4 weeks (Cycle 1-28-Day cycle). From Cycle 2 onwards, on Day 1 of each subsequent 21-day cycle until disease progression (or a total of 6 cycles \[19 weeks\] of study).
• Препарат CHO-H01 at RP2D
  Subjects will be administered intravenous (IV) infusion of RP2D level of CHO-H01, once a week for 4 weeks (Cycle 1-28-Day cycle). From Cycle 2 onwards, on Day 1 of each subsequent 28-day cycle until disease progression (or a total of 6 cycles \[19 weeks\] of study).
• Препарат Lenalidomide
  Subjects will receive oral lenalidomide 20 mg once daily from Day 1 to Day 21 per 28-day cycle.

Первичные конечные точки

• Number of subjects with adverse events (AE) [Срок оценки: Through study completion, approximately 16 months]
• Number of subjects with dose-limiting toxicities [Срок оценки: Through study completion, approximately 16 months]
• Objective Response Rate [Срок оценки: Through study completion, approximately 16 months]
• Best overall response [Срок оценки: Through study completion, approximately 16 months]

Вторичные конечные точки (8)

• Serum concentration of CHO-HO1 [Срок оценки: Through study completion, approximately 16 months]
• Serum Antidrug antibody (ADA) concentration [Срок оценки: Through study completion, approximately 16 months]
• Clinical benefit rate [Срок оценки: Through study completion, approximately 16 months]
• Time to event endpoints of time to progression (TTP) [Срок оценки: Through study completion, approximately 16 months]
• Duration of stable disease [Срок оценки: Through study completion, approximately 16 months]
• Progression-free survival [Срок оценки: Through study completion, approximately 16 months]
• Duration of response [Срок оценки: Through study completion, approximately 16 months]
• Overall survival [Срок оценки: Through study completion, approximately 16 months]

Критерии участия

Критерии включения

• Life expectancy of >12 weeks.
• Body mass index of 18 to 32 kg/m2.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Phase I: Have histologically (laboratory test) confirmed CD20 + non-Hodgkin's lymphoma according to the World Health Organization's 2016 classification:

• Low grade lymphoma: follicular lymphoma (Grades 1-3a), marginal zone lymphoma, small lymphocytic lymphoma;
• Other lymphoma: DLBCL (NOS: to include germinal center B-cell-like \[GCB\] and activated B-cell-like \[ABC\]), follicular lymphoma Grade 3b, mantle cell lymphoma; primary mediastinal large B-cell lymphoma.
• Phase IIa: Histologically confirmed CD20 + non-Hodgkin's lymphoma according to the World Health Organization's 2016 classification, only low grade lymphoma: follicular lymphoma (Grades 1-3a), marginal zone lymphoma, small lymphocytic lymphoma.
• Have at least one measurable lesion that is at least 1.5 cm in its largest dimension.
• Off treatment for 30 days from last anti-CD20 infusion until planned administration of CHO-H01.
• If no original sample is available, is willing and able to provide an adequate tumor biopsy sample at Screening.
• Have adequate cardiac function: without clinically significant and/or uncontrolled heart disease.
• Must be sterile, or have a monogamous partner who is surgically sterile, or at least 2 years postmenopausal, or be committed to use an acceptable form of birth control for the duration of the study (male), and for the duration of the study and for 3 months following the last CHO-H01 administration (female).

Критерии исключения

• Must not have a history of egg allergy or allergic reactions to any component of CHO-H01.
• Must not have any known or current illnesses (such as autoimmune disease, unless well controlled or resolved), infection, or other condition that could limit study compliance or interfere with assessments.
• Subjects who have received anti-programmed death-ligand 1 (PD-L1), programmed cell death 1 (PD-1), or cytotoxic T-lymphocyte associated protein 4 (CTLA-4) therapy.
• Subjects who have completed an autologous stem cell transplant within 100 days prior to CHO-H01 therapy or an allogeneic stem cell transplant.
• Subjects with known hepatitis B surface antigen (HBsAg) seropositive or known or suspected active hepatitis C infection with detectable viral load.
• Subjects with known human immunodeficiency virus (HIV) infection
• Subjects who have had radiation therapy, major surgical procedure or live vaccinations within 28 days prior to CHO-H01 administration.
• Subjects with a history of type I hypersensitivity or anaphylactic reactions to murine proteins or to previous infusions of CD20 monoclonal antibodies.
• Subjects who have received (or are receiving) systemic corticosteroids:

• At a daily dose higher than 15 mg prednisone or equivalent within 14 days prior to the first administration of CHO-H01;
• Topical, inhaled, nasal, and ophthalmic steroids are allowed.
• Inadequate bone marrow, hepatic or renal function.
• Subjects with a history of seizure disorder.
• Subjects who are pregnant or breast feeding.
• Subjects with any contraindications to lenalidomide (Only for phase IIa).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Тайвань · 9 центров

• Tri-Service General Hospital - Neihu Branch - Hematology — Taipei
• Taipei Medical University - Shuang Ho Hospital - Oncology — New Taipei City
• National Taiwan University Hospital Yunlin Branch — Huwei
• Chi-Mei Medical Center — Tainan
• Chang Gung Medical Foundation - LinKou Chang Gung Memorial Hospital - Hematology and Oncol — Taoyuan
• Chang Gung Medical Foundation - Kaohsiung Chang Gung Memorial Hospital - Hemato-Oncology — Kaohsiung City
• China Medical University Hospital - Hematology/Oncology - Taichung — Taichung
• National Cheng Kung University Hospital - Internal Medicine — Tainan
• … и ещё 1 центр

Идентификаторы

NCT: NCT05950165 · NHLHAT-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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