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

Overview

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.

Interventions

• Drug Fully Human Anti-CD19/CD22 Dual Target Chimeric Antigen Receptor Autologous T Cell Injection
  CT120 is an autologous CD19/22 targeted CAR-T cells injection. The dosage form is a cryopreserved injection solution. The T cells aphesis from subjects then been manufactured to express CAR to binding CD19 and CD22 on B-cell lymphoma.

Primary outcome measures

• Phase 1: Types and incidence of Dose-limiting toxicity (DLT) [Time frame: up to 28 days after CT120 infusion]
• Phase 1:Types and incidence of adverse events (AEs) ，serious adverse events (SAEs) and adverse events of special interest (AESI) [Time frame: Up to 2 years after CT120 CAR T-cells infusion]
• Phase 2:Overall response rate (ORR) at Day 90 [Time frame: Up to 90 Days after CT120 infusion]

Secondary outcome measures (11)

• Overall response rate (ORR) [Time frame: Up to Day 28、Day 90、Day180 after CT120 infusion]
• Time to Response (TTR) [Time frame: Up to 2 years after CT120 infusion]
• Time to complete Response (TTCR) [Time frame: Up to 2 years after CT120 infusion]
• Duration of Response (DOR) [Time frame: Up to 2 years after CT120 infusion]
• Progression-free Survival (PFS) [Time frame: Up to 2 years after CT120 infusion]
• Overall Survival (OS) [Time frame: Up to 2 years after CT120 infusion]
• Quantity of CAR copies in peripheral blood [Time frame: Up to 2 years after CT120 infusion]
• Quantity of CAR T-cells level in peripheral blood [Time frame: Up to 2 years after CT120 infusion]
• Laboratory tests [Time frame: Up to 2 years after CT120 infusion]
• Vital signs [Time frame: Up to 2 years after CT120 infusion]
• Physical examination [Time frame: Up to 2 years after CT120 infusion]

Eligibility criteria

Inclusion criteria

• Age between 18 and 70 years old.
• 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:

• 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;
• Recurrence after autologous hematopoietic stem cell transplantation;
• 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:

• The long axis of the lymph node lesions should be ≥15mm (and the length of the short axis is measurable), or;
• 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:

• 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);
• Blood coagulation function: fibrinogen≥1.0g/L; activated partial thromboplastin time≤1.5×ULN, prothrombin time (PT)≤1.5×ULN;
• Liver function: ALT and AST≤2.5×ULN; serum total bilirubin≤1.5×ULN;
• Renal function: creatinine clearance rate CrCl ≥60 mL/min estimated by Cockcroft-Gault;
• Left ventricular ejection fraction (LVEF)≥50% estimated by echocardiography;
• 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

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT05091541 · CT120C001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗