Active, not recruiting
Phase 1/2
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
Condition(s) studied
Non-Hodgkin Lymphoma
Investigational drug(s) / intervention(s)
CHO-H01CHO-H01 at RP2DLenalidomide
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).
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).
Lenalidomide: Subjects will receive oral lenalidomide 20 mg once daily from Day 1 to Day 21 per 28-day cycle.
Study summary
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.
Eligibility
Inclusion Criteria:
* 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:
1. Low grade lymphoma: follicular lymphoma (Grades 1-3a), marginal zone lymphoma, small lymphocytic lymphoma;
2. 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).
Exclusion Criteria:
* 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:
1. At a daily dose higher than 15 mg prednisone or equivalent within 14 days prior to the first administration of CHO-H01;
2. 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).
Primary outcome measure(s)
- Number of subjects with adverse events (AE) — Through study completion, approximately 16 months
To assess the safety and tolerability of CHO-H01 as a single agent in subjects with relapsed/refractory CD20 + non-Hodgkin's lymphoma and CHO-H01 plus lenalidomide in subjects with low-grade relapsed/refractory CD20 + non-Hodgkin's lymphoma.
- Number of subjects with dose-limiting toxicities — Through study completion, approximately 16 months
All AEs and toxicities are evaluated based on the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) Version 5.0. The 5 general grades are Grade 1: Mild, Grade 2: Moderate, Grade 3: Severe, Grade 4: Life-threatening or disabling, and Grade 5: Death (outcome of AE).
- Objective Response Rate — Through study completion, approximately 16 months
Objective response rate (ORR) is the proportion of subjects with a best overall response of complete response (CR) or partial response (PR). ORR will be measured based on Modified (not using PET imaging) Lugano Revised Criteria for Response assessment.
- Best overall response — Through study completion, approximately 16 months
The best overall response (CR, PR, stable disease \[SD\], or progressive disease \[PD\]) is defined as the best response across all time points.
Trial sites (9)
| Facility | City | Region | Status |
| Tri-Service General Hospital - Neihu Branch - Hematology |
Taipei |
Taipei |
|
| Taipei Medical University - Shuang Ho Hospital - Oncology |
New Taipei City |
Taipei Special Municipality |
|
| National Taiwan University Hospital Yunlin Branch |
Huwei |
Taiwan |
|
| Chi-Mei Medical Center |
Tainan |
Taiwan |
|
| Chang Gung Medical Foundation - LinKou Chang Gung Memorial Hospital - Hematology and Oncology - Hematology and Oncology |
Taoyuan |
Taoyuan |
|
| Chang Gung Medical Foundation - Kaohsiung Chang Gung Memorial Hospital - Hemato-Oncology |
Kaohsiung City |
Taiwan |
|
| China Medical University Hospital - Hematology/Oncology - Taichung |
Taichung |
Taiwan |
|
| National Cheng Kung University Hospital - Internal Medicine |
Tainan |
Taiwan |
|
| National Taiwan University Hospital - Hematology And Oncology |
Taipei |
Taiwan |
|
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