Trial Title:
A Prospective Clinical Study of CD3-CD20 Bisspecific Antibody Based Therapy Combined With CD19-CAR T Cells in the Treatment of Relapsed Refractory B-cell Non-Hodgkin Lymphoma
NCT ID:
NCT06464185
Condition:
B-cell Non-Hodgkin Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Antibodies
Antibodies, Bispecific
Conditions: Keywords:
Glofitamab
CAR-T
obinutuzumab
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:
Bispecific antibody-based combined with CAR-T cell therapy
Description:
lymphocytes collection, and bispecific antibody-based therapy will be performed after
successful Lymphocytes collection: Obinutuzumab:1000mg, cycle 1 day 1(C1D1) ,IV.
Glofitamab: 2.5 mg, C1D8; 10 mg,C1D15 ; 30 mg,C2D1 and C3D1, IV. It can be combined with
other Immunization therapy during the use of bispecific antibodies according to the
patient's condition.
On C4D1, the patient will be pretreated with fludarabine and cyclophosphamide (FC)
regimen, and then infused with CART cells at a specific dose of 4 * 1000000/Kg.
Bispecific antibody maintenance therapy will be initiated on month 1/2/3 after CART
infusion. In Phase1 bispecific maintenance therapy will be divided into three dose
groups, using a "3 + 3" dose escalation design. In Phase 2, bispecific maintenance
therapy will be used at the MTD dose of Phase 1.
Arm group label:
Bispecific antibody-based therapy combined with CAR-T cell therapy
Summary:
The aim of this study was to analyze the safety and efficacy of CD3-CD20 bispecific
antibody-based therapy in combination with CD19-CAR-T cells for the treatment of relapsed
and refractory B-cell Non-Hodgkin's （B-NHL） lymphoma.
The main questions it aims to answer：
1. The safety of CD3-CD20 bispecific antibody-based therapy in combination with
CD19-CAR-T cells in B-NHL;
2. The effect of different doses of bispecific antibody maintenance therapy on CAR-T
cell expansion.
Detailed description:
The study was divided into two phases:
In the previous phase Ib clinical study, the bispecific antibody was used for bridging
therapy to reduce the Neoplasm load, followed by CART cell therapy. After CART cell
therapy, low-dose bispecific antibody was used for maintenance, in order to explore the
safe resistance of bispecific antibody combined with CAR-T cell therapy and further
explore the effect of bispecific antibody combined with CAR-T cell therapy on CART cell
expansion; Phase II study will expand the sample study to further clarify whether
bispecific antibody combined with CAR-T cell therapy can further deepen the efficacy of
CAR-T.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- The patient has fully understood the study and voluntarily signed the informed
consent form (ICF)
- Must meet the diagnostic criteria for relapsed and refractory B-NHL and have
evaluable disease lesions, in addition to the following characteristics for
different types of B-NHL:
A, Diffuse large B-cell Lymphoma:
Patients with histologically confirmed DLBCL; Patients who must have received
,anthracyclines CD20 monoclonal antibodies and BTK inhibitors and other Drug therapy, and
have received at least two lines of treatment and relapsed, not relieved or progressed
within 24 months after the last line of treatment;
B, Relapsed and Refractory Follicular lymphoma (FL):
Tissue Biopsy proved FL: grade 1-3a; Must have received anthracyclines and CD20
monoclonal antibody Drug therapy, and have received at least two lines of treatment and
relapsed, not remitted or progressed within 24 months after the last line of treatment;
C, Relapsed and Refractory Marginal zone lymphoma (MZL):
Histologically unequivocally confirmed MZL; Must have received anthracyclines and CD20
monoclonal antibody Drug therapy, and have received at least two lines of treatment and
relapsed, not remitted or progressed within 24 months after the last line of treatment;
D, Relapsed and refractory Mantle cell lymphoma (MCL):
Histologically confirmed MCL; Relapsed or refractory after at least 2 lines of therapy
(including anti-CD20 monoclonal antibody, anthracyclines or bendamustine, and BTKi);
E, Relapsed and refractory CLL:
Histologically confirmed CLL; Patients who have received at least Immunochemotherapy and
have Drug therapy to both BTK inhibitors and BCL2 inhibitors Drug resistance;
F, Relapsed and refractory WM:
Patients with histologically confirmed WM; Patients who must have received
anthracyclines, CD20 monoclonal antibodies and BTK inhibitors and other Drug therapy, and
have received at least two lines of treatment and relapsed, not relieved or progressed
within 24 months after the last line of treatment;
- ECOG score 0-1
- Laboratory test: Neutrophils 0.5 x 10 ^ 9/L; platelets 30 x 10 ^ 9/L; Bilirubin
total 2 x upper limit; GPT/Glutamic-oxaloacetic transferase 3 x upper limit.
Creatinine clearance ≥ 30 mL/min.
- The expected survival time of patients is ≥ 6 months;
Exclusion Criteria:
- Neoplasm malignant other than B-NHL (except active central nervous system lymphoma)
diagnosed or treated within the past year; Patients who received anti Neoplasm
therapy (including chemotherapy, targeted therapy, hormone therapy, traditional
Chinese medicine with anti neoplasm activity, etc.) or participated in other
clinical trials and received the investigational drug within 4 weeks before the
first use of the investigational drug;
- Liver renal impairment not related to lymphoma: GPT (ALT) > 3 times the upper limit
of normal, glutamic-oxaloacetic transferase (AST) > 3 times the upper limit of
normal, bilirubin total (TBIL) > 2 times the upper limit of normal, serum creatinine
clearance rate < 30ml/min;
- Other serious medical diseases that will affect the study (such as uncontrolled
Diabetes mellitus, gastric ulcer, other serious heart lung disease, etc.), and the
right to decide belongs to the investigator.
- Cardiac function and disease meet one of the following conditions:
A, Long QTc syndrome or QTc interval > 480 MS; B, Complete left bundle branch block,
grade II or III AV block; C, Serious, uncontrolled arrhythmia requiring drug therapy; D,
New York Heart Association Heart disorder grade ≥ III; E, Cardiac Ejection Fraction
(LVEF) less than 50%; F, Ischaemia, unstable Angina pectoris, history of severe unstable
Ventricular arrhythmia or any other Arrhythmia requiring treatment, history of clinically
significant Pericardial disease, or Electrocardiogram evidence of acute Myocardial
infarction or active conduction system abnormalities within 6 months prior to
recruitment;
- Known history of Infection human Immunodeficiency virus (HIV) or active Hepatitis B
virus (HBV) Infection, or any uncontrolled active Injection requiring intravenous
Systemic infection of antibiotics; Patients in the past 14 days received a large
surgery (excluding lymph node Biopsy) or expected treatment in the need for a large
Surgery;
- Previous or current other neoplasm malignant (except effectively controlled skin
Basal cell carcinoma without melanoma, breast/In situ cancer of cervix, and other
effectively controlled Neoplasm malignant without treatment within the past five
years
- Pregnancy or lactating women, women of childbearing age who did not take
contraception measures;
- Hypersensitivity to the drugs or ingredients used;
Gender:
All
Minimum age:
18 Years
Maximum age:
80 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Institute of Hematology and Blood Diseases Hospital ,Chinese Academy of Medical Sciences
Address:
City:
Tianjin
Country:
China
Status:
Recruiting
Contact:
Last name:
Shuhua Yi, Dr
Phone:
86-22-23608109
Email:
yishuhua@ihcams.ac.cn
Start date:
April 30, 2024
Completion date:
April 30, 2027
Lead sponsor:
Agency:
Institute of Hematology & Blood Diseases Hospital, China
Agency class:
Other
Source:
Institute of Hematology & Blood Diseases Hospital, China
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06464185
