Trial Title:
A Study of GNC-035 in Relapsed or Refractory Chronic Lymphocytic Leukemia and Other Hematological Malignancies
NCT ID:
NCT05944978
Condition:
Relapsed/Refractory Chronic Lymphocytic Leukemia
Conditions: Official terms:
Leukemia
Neoplasms
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
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 intravenously infused 2h to 4h, once a week (IV, QW), and a 3-week cycle was
used.
Arm group label:
Study treatment
Summary:
An open-label, multicenter, phase Ib/II clinical trial was conducted to evaluate the
safety, tolerability, pharmacokinetics/pharmacodynamics, and antitumor activity of
GNC-035 quad-specific antibody injection in patients with relapsed or refractory chronic
lymphocytic leukemia and other hematological malignancies
Detailed description:
Phase Ib: To observe the safety and tolerability of GNC-035 in patients with hematologic
malignancies such as relapsed/refractory chronic lymphocytic leukemia, and to determine
the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD), or maximum dose if MTD
is not reached (MAD), of GNC-035. To determine the recommended phase II dose (RP2D) in
hematologic malignancies such as chronic lymphocytic leukemia. Phase II: To explore the
efficacy of GNC-035 in patients with relapsed/refractory chronic lymphocytic leukemia 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 (≤75 years old for climbing);
4. expected survival time ≥3 months;
5. Patients with hematological malignancies such as relapsed/refractory chronic
lymphocytic leukemia confirmed by histology or cytology;
6. For relapsed or refractory chronic lymphocytic leukemia (CLL/SLL), specifically:
Patients who have relapsed after at least one line of standard therapy or have no
response to or intolerance to standard regimens; Patients with relapsed or
refractory chronic lymphocytic leukemia who were not or were ineligible
for/intolerant of other therapies according to investigator assessment.
Relapsed and refractory were defined as follows:
Relapse was defined as disease progression after a response to adequate treatment,
including at least one regimen containing a BTK inhibitor.
Refractory was defined as refractory to BTK inhibitor, failure to achieve remission
after adequate treatment with BTK inhibitor-containing regimens (combination therapy
or monotherapy), or disease progression during treatment or within 6 months after
completion of adequate treatment.
7. For other patients with relapsed refractory non-Hodgkin lymphoma. These include:
Patients who experience failure of at least two lines of therapy; Relapsed or
refractory patients who are not or are ineligible for/intolerant of other therapies
as judged by the investigator.
Relapsed and refractory were defined as follows:
Relapse was defined as disease progression after a response to adequate treatment,
including 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
(combination therapy or monotherapy), or disease progression during treatment or 6
months after completion of adequate treatment.
Among them, "adequate treatment with anti-CD20 monoclonal antibody" refers to the
completion of full cycle of anti-CD20 monoclonal antibody combined with chemotherapy
according to pathological type and disease stage, or anti-CD20 monoclonal antibody
monotherapy at a dose of 375 mg/m2 once a 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.
8. CLL/SLL: peripheral blood leukemia cells ≥5.0×109/L; Or the long diameter of any
lymph node lesion ≥1.5cm; Patients with non-Hodgkin's lymphoma had measurable
disease at screening (nodal disease ≥1.5cm in the greatest dimension or extranodal
disease > 1.0cm in the greatest dimension).
9. ECOG ≤2;
10. Toxicity of previous antineoplastic therapy has returned to ≤ grade 1 defined by
NCI-CTCAE v5.0 (except alopecia);
11. Organ function within 7 days before the first dose:
Bone marrow function (for patients with non-Hodgkin lymphoma only) : 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 or creatinine clearance (Ccr) ≥60 mL/ minute
(based on center calculation criteria) Coagulation: activated partial thromboplastin
time (APTT) ≤1.5×ULN Prothrombin time (PT) ≤1.5×ULN.
12. 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;
13. 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. Severe systemic infection occurred within 4 weeks before screening, including but
not limited to severe pneumonia caused by fungi, bacteria, or viruses, bacteremia,
or serious infectious complications;
4. Patients with active autoimmune disease or a history of autoimmune disease. Patients
with type I diabetes mellitus, hypothyroidism that is stable with
hormone-replacement therapy (including hypothyroidism due to autoimmune thyroid
disease), psoriasis, or vitiligo that does not require systemic therapy, as deemed
by the investigators, were excluded.
5. Patients with other malignant tumors within 3 years before the first drug
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 3 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 > 150 mmHg
or diastolic blood pressure > 100 mmHg);
8. Left ventricular ejection fraction ≤45%, or history of major heart disease within 1
year:
1. New York Heart Association (NYHA) class III or IV congestive heart failure;
2. Acute coronary syndrome, myocardial infarction or bypass or stent surgery
(except those judged by the investigator to be stable);
3. Patients with unstable angina pectoris;
4. QT prolongation (QTcf > 450 msec in men or > 470 msec in women), complete left
bundle branch block, degree III atrioventricular block, and arrhythmia
requiring medical intervention;
5. Other cardiac conditions deemed by the investigator to be ineligible for
enrollment.
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. Presence of central nervous system invasion;
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. Received anti-CD20 therapy within 4 weeks prior to GNC-035 therapy and is
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:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences
Address:
City:
Tianjin
Zip:
300020
Country:
China
Status:
Recruiting
Contact:
Last name:
Yali Zhang
Phone:
022-23909095
Email:
ec@ihcams.ac.cn
Investigator:
Last name:
Lugui Qiu
Email:
Principal Investigator
Investigator:
Last name:
Shuhua Yi
Email:
Principal Investigator
Start date:
August 16, 2023
Completion date:
August 2025
Lead sponsor:
Agency:
Sichuan Baili 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/NCT05944978
