Trial Title:
A Study of GNC-035 in Relapsed or Refractory Non-Hodgkin 's Lymphoma and Other Hematological Malignancies
NCT ID:
NCT06066203
Condition:
Non-hodgkin's Lymphoma
Conditions: Official terms:
Lymphoma
Neoplasms
Hematologic Neoplasms
Conditions: Keywords:
Hematological malignancies
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
GNC-035
Description:
GNC-035 was administered by intravenous infusion for 2 h-4 h, once a week ( IV, QW ), 3
weeks as a cycle.
Arm group label:
Study treatment
Summary:
Phase I main objectives: To observe the safety and preliminary efficacy of GNC-035 in
patients with relapsed/refractory non-Hodgkin lymphoma and other hematological
malignancies, to determine the DLT and MTD, or MAD, and to determine RP2D. Phase II Main
objective: To explore the efficacy of GNC-035 in patients with relapsed/refractory
non-Hodgkin lymphoma and other hematological malignancies.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Subjects can understand the informed consent form, voluntarily participate in and
sign the informed consent form.
2. No gender limit.
3. Age: ≥18 years old and ≤75 years old.
4. Expected survival time ≥3 months.
5. Histologically or cytologically confirmed relapsed/refractory non-Hodgkin lymphoma.
6. For patients with relapsed/refractory non-Hodgkin lymphoma. These include:
Patients who experience failure of at least one line of standard therapy. Patients
with relapsed or refractory disease who were not or not suitable for other therapies
as judged by the investigator.
Relapsed and refractory were defined as follows:
Relapse was defined as disease progression after 6 months of response to adequate
treatment with at least one anti-CD20 monoclonal antibody.
Refractory was defined as refractory to anti-CD20 monoclonal antibody, failure to
achieve remission after adequate treatment with anti-CD20 monoclonal antibody
(combined chemotherapy or single agent), or disease progression during treatment or
6 months after completion of adequate treatment.
Among them, "anti-CD20 monoclonal antibody regimen adequate treatment" refers to the
completion of the full cycle of anti-CD20 monoclonal antibody combined with
chemotherapy according to the pathological type and disease stage, such as rituximab
monotherapy at a dose of 375 mg/m2 per week for at least 4 injections. Progression
during treatment required the completion of at least one cycle of anti-CD20
monoclonal antibody combined with chemotherapy or monotherapy if progression
occurred during induction therapy. At least one dose was completed if progression
occurred during maintenance therapy. "Response" included complete and partial
responses.
7. For non-Hodgkin lymphoma, at least one lesion must be evaluable during the uphill
phase; The extension stage had to have at least one measurable lesion according to
the Lugano criteria (lymph node lesion ≥1.5cm or extranodal lesion > 1.0cm).
8. ECOG ≤2.
9. Toxicity of previous antineoplastic therapy has returned to grade 1 or less as
defined by NCI-CTCAE v5.0 (except for those indicators considered by the
investigator to be possibly related to the disease, such as anemia, and those judged
by the investigator to have no safety risk, such as alopecia, grade 2 peripheral
neurotoxicity, and hypothyroidism stable with hormone replacement therapy).
10. Organ function within 7 days before the first dose:
Bone marrow function: without blood transfusion, G-CSF (for 2 weeks), and medication
correction within 7 days prior to screening Absolute neutrophil count (ANC)
≥1.0×109/L (≥0.5×109/L if the subject has bone marrow infiltration); Hemoglobin ≥80
g/L (≥70g/L if the subject has bone marrow infiltration); Platelet count ≥75×109/L;
Liver function: total bilirubin, ≤1.5 ULN (Gilbert's syndrome, ≤3 ULN), and
aminotransferase (AST/ALT), ≤2.5 ULN (for those with liver tumor invasive changes,
≤5.0 ULN) without correction with hepatoprotective medication within 7 days before
screening examination Renal function: creatinine (Cr) ≤1.5 ULN and creatinine
clearance (Ccr) ≥50 mL/ minute (according to Cockcroft and Gault formula) Urinalysis
/ 24-hour urine protein quantification: qualitative urine protein ≤1+ (if
qualitative urine protein ≥2+, 24-hour urine protein < 1g is eligible) Cardiac
function: left ventricular ejection fraction ≥50% Coagulation: fibrinogen ≥1.5g/L
Activated partial thromboplastin time (APTT) ≤1.5×ULN; Prothrombin time (PT)
≤1.5×ULN.
11. Female subjects of childbearing potential or male subjects with a fertile partner
must use highly effective contraception from 7 days before the first dose until 12
weeks after the last dose. Female subjects of childbearing potential must have a
negative serum/urine pregnancy test within 7 days before the first dose.
12. Participants were able and willing to comply with protocol-specified visits,
treatment plans, laboratory tests, and other study-related procedures.
Exclusion Criteria:
1. Patients who underwent major surgery within 28 days before study administration or
who were scheduled to undergo major surgery during the study (" major surgery "was
defined by the investigator).
2. Pulmonary disease grade ≥3 according to NCI-CTCAE v5.0, including dyspnea at rest or
requiring continuous oxygen therapy; Patients with current interstitial lung disease
(ILD) (except those who have recovered from previous interstitial pneumonia).
3. Active infections requiring systemic therapy, such as severe pneumonia, bacteremia,
sepsis, etc.
4. patients with active autoimmune diseases, such as systemic lupus erythematosus,
psoriasis requiring systemic treatment, rheumatoid arthritis, inflammatory
intestinal diseases and Hashimoto's thyroiditis, etc., excluding type I diabetes
mellitus, hypothyroidism that can be controlled only by replacement therapy, skin
diseases without systemic treatment (such as vitiligo, psoriasis), etc.
5. Patients with other malignant tumors within 5 years before the first administration,
cured non-melanoma skin cancer in situ, superficial bladder cancer, cervical cancer
in situ, gastrointestinal mucosal cancer, breast cancer, localized prostate cancer,
and other patients without recurrence within 5 years were excluded.
6. Human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, active
hepatitis B virus infection (HBsAg positive or HBcAb positive and HBV-DNA test ≥
central detection lower limit) or hepatitis C virus infection (HCV antibody positive
and HCV-RNA≥ central detection lower limit).
7. Hypertension poorly controlled by medication (systolic blood pressure > 160 mmHg
or diastolic blood pressure > 100 mmHg).
8. A history of severe cardiovascular and cerebrovascular disease, including but not
limited to:
Severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias
requiring clinical intervention, grade III atrioventricular block, etc.
Prolonged QT interval at rest (QTc > 450 msec in men or QTc > 470 msec in women)
Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or
other grade 3 or higher cardio-cerebrovascular event occurring within 6 months
before the first dose.
New York Heart Association (NYHA) class ≥II HF.
9. Patients with a history of allergy to recombinant humanized antibodies or to any of
the excipients of GNC-035.
10. Women who are pregnant or breastfeeding.
11. Patients with central nervous system involvement.
12. Prior organ transplantation or allogeneic hematopoietic stem cell transplantation
(ALLo-HSCT).
13. Autologous hematopoietic stem cell transplantation (Auto-HSCT) within 12 weeks
before starting GNC-035 therapy.
14. Current use of immunosuppressive agents, including, but not limited to,
cyclosporine, tacrolimus, etc., within 2 weeks or 5 half-life periods prior to
GNC-035 treatment, whichever is shorter.
15. Received radiotherapy, macromolecular targeted drugs within 4 weeks before GNC-035
treatment; Chemotherapy and a small-molecule targeted agent were administered 2
weeks or within five half-lives before treatment, whichever was less.
16. Have received anti-CD20 or anti-CD79b therapy within 4 weeks before starting GNC-035
and are responding.
17. Received CAR-T therapy within 12 weeks before GNC-035 treatment.
18. Use of a study drug from another clinical trial within 4 weeks or 5 half-lives,
whichever was shorter, before the trial dose.
19. Other circumstances that the investigator deemed inappropriate for participation in
the trial.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Beijing Cancer Hospital
Address:
City:
Beijing
Country:
China
Status:
Recruiting
Contact:
Last name:
Jun Zhu, PHD
Phone:
88196115
Email:
zhujun3346@163.com
Start date:
November 1, 2023
Completion date:
November 2025
Lead sponsor:
Agency:
Sichuan Baili Pharmaceutical Co., Ltd.
Agency class:
Industry
Collaborator:
Agency:
Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.
Agency class:
Industry
Source:
Sichuan Baili Pharmaceutical Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06066203
