Clinical trial NCT05091541: A Phase 1/2 Study of CT120 in Patient With Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma
Official title: A Multicenter Phase I/II Clinical Study on Fully Human Anti-CD19/CD22 Dual Target Chimeric Antigen Receptor Autologous T Cell Injection (CT120) for the Treatment of Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: B-cell Non-Hodgkin's Lymphoma
Lead sponsor: Nanjing IASO Biotechnology Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-10-25
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is a single-armed, open-label,multicenter Phase 1/2 study to evaluate the safety and efficacy of CT120 in subjects with relapsed/refractory B-cell non-Hodgkin's lymphoma.

Detailed description: Leukapheresis procedure will be performed to manufacture CT120. Bridging therapy is allowed between PBMC collection and lymphodepletion. Lymphodepletion with fludarabine and cyclophosphamide was performed for three consecutive days. After 1-day rest, subjects will receive a single dose infusion of CT120. Subjects will be followed in the study for a minimum of 2 years after CT120 infusion. Long-term follow-up for lentiviral vector safety will be followed for up to 15 years after CT120 infusion.

Eligibility criteria: Inclusion Criteria:

1. Age between 18 and 70 years old.
2. Pathologically confirmed B-cell non-Hodgkin's lymphoma, including:

(1) Diffuse large B-cell lymphoma (DLBCL); (2) Histopathological Grade 3b follicular lymphoma (FL3b); (3) Follicular lymphoma with diffuse large B cell transformation; (4) Primary mediastinal large B-cell lymphoma (PMBCL). 3. Relapsed/refractory B-cell non-Hodgkin's lymphoma must meet one of the following criteria:

1. At least 2 failed prior B-cell non-Hodgkin's lymphoma treatment regimens (including relapse, no response, and progression). Prior therapy must have included anti-CD20 monoclonal antibodies (except for CD20-negative subjects) and standard therapies which including anthracyclines;
2. Recurrence after autologous hematopoietic stem cell transplantation;
3. Primary resistance: After 2 cycles of initial anti-CD20 monoclonal immunochemotherapy, the best response was stable disease or disease progression.

4. At least 1 measurable lesion as following:

1. The long axis of the lymph node lesions should be ≥15mm (and the length of the short axis is measurable), or;
2. The lengths of extra-lymph node lesions should be ≥10mm in both the long and short axis.

5. Expected survival time≥12 weeks. 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 7. Adequate organ function before enrollment, and meet all the following laboratory test results:

1. Blood routine: neutrophils ≥1.0 ×109/L (granulocyte colony stimulating factor (G-CSF) is allowed within 7 days before the examination), lymphocytes ≥0.3 ×109 /L, platelets ≥50 ×109 /L (must have not received blood transfusion \[including component transfusion\] or treatments that include thrombopoietin \[TPO\] for the purpose of raising platelets within 7 days before the examination), hemoglobin ≥80g/L (must have not received blood transfusion \[including component blood transfusion\] within 7 days before the examination);
2. Blood coagulation function: fibrinogen≥1.0g/L; activated partial thromboplastin time≤1.5×ULN, prothrombin time (PT)≤1.5×ULN;
3. Liver function: ALT and AST≤2.5×ULN; serum total bilirubin≤1.5×ULN;
4. Renal function: creatinine clearance rate CrCl ≥60 mL/min estimated by Cockcroft-Gault;
5. Left ventricular ejection fraction (LVEF)≥50% estimated by echocardiography;
6. Baseline oxygen saturation \> 91% on room air. 8. Females and males with childbearing potential should take effective contraception from the day of signing the informed consent form to 365 days after the CT120 infusion. Effective contraception is defined as: abstinence or contraceptive methods with an annual failure rate of \<1% indicated in section 9.8 of this protocol.

9. Subject is willing to participate in this trial and sign an informed consent form.

Exclusion Criteria:

1. Subjects who have received or require the following treatments:

(1) Prior CAR-T cell therapy before enrollment; (2) Presence of acute or chronic graft-versus-host disease (GVHD) requires systemic treatment within 4 weeks before enrollment; (3) History of immunodeficiency or other diseases and autoimmune diseases (eg Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus, etc.) received immunosuppressive therapy within 2 years before enrollment; (4) Autologous hematopoietic stem cell transplantation (autoSCT) within 12 weeks before enrollment and history of allogeneic stem cell transplantation (HSCT); (5) Live vaccines injection within 4 weeks before enrollment; (6) According to investigator's discretion, there is a need to use systemic corticosteroid therapy within 12 weeks after the administration of the study drug (except for hydrocortisone ≤12mg/m2/day or other hormones converting into the same dose range for physiological replacement therapy) or other immunosuppressive drug therapy (except local therapy).

2. B-cell non-Hodgkin's lymphoma patients with active central nervous system or intestinal parenchyma invasion.

3. Excessive tumor burden and any lesions with a long axis ≥10cm. 4. Other active malignant tumors in the past 5 years, except for curable tumor that has been completely cured, such as basal or squamous cell carcinoma, cervical or breast carcinoma in situ, etc.

5. Positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and an abnormal HBV DNA result detected by peripheral blood test (abnormal HBV DNA result is defined as: the quantitative detection of HBV DNA is over the detectable lower limit or beyond the normal reference of the testing center or HBV viral DNA positive); Hepatitis C virus (HCV) antibody positive and peripheral blood HCV RNA positive; Human immunodeficiency virus (HIV) antibody positive; Cytomegalovirus (CMV) DNA test positive; syphilis test positive.

6. Uncontrollable active infections (except for genitourinary system infections and upper respiratory tract infections \< CTCAE Grade 2).

7. Severe heart disease: including but not limited to unstable angina, myocardial infarction (within 6 months before screening), congestive heart failure (New York Heart Association \[NYHA\] classification ≥ Grade III), severe arrhythmia.

8. Hypertension that cannot be controlled by medication. 9. Adverse events during prior therapies have not relieved to baseline or ≤1 (according to NCI-CTCAE v5.0, except for alopecia).

10. Major surgery within 2 weeks before enrollment, or surgeries that were planed while waiting for infusion or within 12 weeks after receiving investigational product (except planned local anesthesia surgery).

11. History of organ transplant. 12. Pregnant or lactating women. 13. Previous central nervous system diseases (such as cerebral aneurysm, epilepsy, stroke, Alzheimer's disease, mental illness, etc.) or mental disorders.

14. Unstable systemic diseases judged by other researchers: including but not limited to severe liver, kidney, or metabolic diseases that require medication.

15. Other unsuitable situations for enrollment judged by investigators.

Primary outcomes:
measure: Phase 1: Types and incidence of Dose-limiting toxicity (DLT)
timeFrame: up to 28 days after CT120 infusion
measure: Phase 1:Types and incidence of adverse events (AEs) ，serious adverse events (SAEs) and adverse events of special interest (AESI)
timeFrame: Up to 2 years after CT120 CAR T-cells infusion
measure: Phase 2:Overall response rate (ORR) at Day 90
timeFrame: Up to 90 Days after CT120 infusion
Secondary outcomes:
measure: Overall response rate (ORR)
timeFrame: Up to Day 28、Day 90、Day180 after CT120 infusion
measure: Time to Response (TTR)
timeFrame: Up to 2 years after CT120 infusion
measure: Time to complete Response (TTCR)
timeFrame: Up to 2 years after CT120 infusion
measure: Duration of Response (DOR)
timeFrame: Up to 2 years after CT120 infusion
measure: Progression-free Survival (PFS)
timeFrame: Up to 2 years after CT120 infusion
measure: Overall Survival (OS)
timeFrame: Up to 2 years after CT120 infusion
measure: Quantity of CAR copies in peripheral blood
timeFrame: Up to 2 years after CT120 infusion
measure: Quantity of CAR T-cells level in peripheral blood
timeFrame: Up to 2 years after CT120 infusion
measure: Laboratory tests
timeFrame: Up to 2 years after CT120 infusion
measure: Vital signs
timeFrame: Up to 2 years after CT120 infusion
measure: Physical examination
timeFrame: Up to 2 years after CT120 infusion
Other outcomes:
measure: Immunogenicity
timeFrame: Up to 2 years after CT120 infusion
measure: Replication competent lentivirus (RCL)
timeFrame: Up to 15 years after CT120 infusion
measure: Changes in the proportion of peripheral blood lymphocyte subsets
timeFrame: Up to 2 years after CT120 infusion
measure: Correlation between cytokines/inflammation-related proteins and Incidence of Adverse Event
timeFrame: Up to 2 years after CT120 infusion
measure: Correlation between cytokines/inflammation-related proteins and efficacy
timeFrame: Up to 2 years after CT120 infusion
measure: Correlation between efficacy and CD19/CD22 antigen expression in tumor tissues
timeFrame: Up to 2 years after CT120 infusion
measure: Correlation between efficacy and gene mutations including MYC, BCL2 and BCL6 rearrangements
timeFrame: Up to 2 years after CT120 infusion
measure: Correlation between efficacy and and the expression of oncogenes including C-myc and BCL
timeFrame: Up to 2 years after CT120 infusion
Locations:
Study officials:
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