GZL Sequential CD19/CD22 CAR-T in Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

NCT ID: NCT05797948

Last Updated: 2023-04-04

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-07-01
• Study Completion Date: 2024-06-30

Brief Summary

This study intends to use Obinutuzumab, Zanubrutinib, and Lenalidomide sequential CD19/CD22 CAR-T in the treatment of Relapsed or Refractory B-cell Non-Hodgkin Lymphoma patients. The main purpose of this study is to explore a new treatment mode for R/R B-NHL patients and observe the efficacy and safety of this treatment regimen.

Detailed Description

The study will start with 2-4 cycles of combination chem-free therapy with obinutuzumab, zanubrutinib and lenalidomide, followed by sequential CAR-T therapy. CAR-T therapy with AZA + FC (Azacitidine +Fludarabine +Cyclophosphamide) conditioning regimen. Targets of CAR-T cells are CD19/CD22. In this clinical trial, ORR, CRR, OS, PFS, AE and other indicators were used to observe the safety and efficacy of this sequential therapy.

Conditions

Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

GZL sequential CD19/CD22 CAR-T

Phase I (combined immunotherapy period):

2-4 cycle of combination chem-free therapy with Obinutuzumab, Zanubrutinib and Lenalidomide . Each cycle is 21 days.

Phase II (CAR-T therapy):

CAR-T therapy with AZA + FC (Azacitidine, Fludarabine and Cyclophosphamide) conditioning regimen. Targets of CAR-T cells are CD19/CD22.

Group Type: EXPERIMENTAL

Obinutuzumab

Intervention Type: DRUG

Obinutuzumab Injection 1000mg ivgtt C1-C4 d1；

Zanubrutinib

Intervention Type: DRUG

Zanubrutinib 160mg (2 capsules) oral bid；

Lenalidomide

Intervention Type: DRUG

Lenalidomide 25mg (1 capsule) oral C1-C4 d1-d10.

CD19/CD22 CAR-T

Intervention Type: DRUG

Targets of CAR-T cells are tandem CD19/CD22. 1 \* 10 \^ 7/kg dual-target CAR-T cells were reinfused with 10%, 30% and 60% of the total dose on d1, d2, d3 respectively.

Azacitidine For Injection

Intervention Type: DRUG

Azacitidine For Injection 100mg i.h. d1-d5;

Fludarabine

Intervention Type: DRUG

Fludarabine 300mg/m2 ivgtt d3-d5;

Cyclophosphamide

Intervention Type: DRUG

Cyclophosphamide 300mg/m2 ivgtt d3-d5.

Interventions

Obinutuzumab

Obinutuzumab Injection 1000mg ivgtt C1-C4 d1；

Intervention Type: DRUG

Zanubrutinib

Zanubrutinib 160mg (2 capsules) oral bid；

Intervention Type: DRUG

Lenalidomide

Lenalidomide 25mg (1 capsule) oral C1-C4 d1-d10.

Intervention Type: DRUG

CD19/CD22 CAR-T

Targets of CAR-T cells are tandem CD19/CD22. 1 \* 10 \^ 7/kg dual-target CAR-T cells were reinfused with 10%, 30% and 60% of the total dose on d1, d2, d3 respectively.

Intervention Type: DRUG

Azacitidine For Injection

Azacitidine For Injection 100mg i.h. d1-d5;

Intervention Type: DRUG

Fludarabine

Fludarabine 300mg/m2 ivgtt d3-d5;

Intervention Type: DRUG

Cyclophosphamide

Cyclophosphamide 300mg/m2 ivgtt d3-d5.

Intervention Type: DRUG

Other Intervention Names

Gazyva; Brukinsa; Anxian; Anyve; Fludara; Endoxan

Eligibility Criteria

Inclusion Criteria

1. Histologically confirmed CD22 + and/or CD19 + aggressive B-cell non-Hodgkin lymphoma (NHL), including the following types as defined by World Health Organization (WHO) 2016:

Diffuse large B-cell lymphoma (DLBCL); High grade B-cell lymphoma (HGBL); Primary mediastinal large B-cell lymphoma(PMBCL); T cell/histiocyte-rich large B-cell lymphoma (THRBCL); High grade follicular cell lymphoma Grade 3b (3bFL); Mantle cell lymphoma (MCL) except indolent; Other aggressive B-cell lymphomas.

2. Disease refractory to first-line therapy or early relapse within 12 months of last treatment.

3. Relapse or progressive disease (PD) ≥ 3 months after targeted CD19 therapy including CD19 CAR T cells or anti-CD19/anti-CD3.

4. Successful leukapheresis assessment and T-cell preculture.

5. Life expectancy > 3 months.

6. Appropriate organ function:

Creatinine < 1.6 mg/dL (140 µmol/L) or creatinine clearance ≥ 60ml/min; Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) < 3 × upper limit of normal; Bilirubin < 2.0 mg/dL unless subject has Gilbert 's syndrome (< 3.0 mg/dL); Pulmonary reserve ≤ Grade 1 dyspnea and SPO2 > 91%; Cardiac ejection fraction ≥ 50% in the absence of oxygen, no evidence of pericardial effusion as determined by echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings.

7. Adequate bone marrow reserve was defined as:

Absolute neutrophil count (ANC) > 1000/mm3; Absolute lymphocyte count (ALC) ≥ 300/mm3; Platelet count ≥ 50,000/mm3. Hemoglobin > 7.0 mg/dL.

8. Measurable or evaluable lesions according to "IWG response criteria for malignant lymphoma" (Cheson 2014).

9. Patients have the ability to understand and are willing to provide written informed consent.

Exclusion Criteria

1. severe liver and kidney dysfunction (alanine aminotransferase, bilirubin, creatinine > 3 times the upper limit of normal);

2. the presence of structural heart disease, and lead to clinical symptoms or abnormal heart function (NYHA ≥ 2);

3. uncontrolled active infection;

4. the presence of other tumors requiring treatment or intervention;

5. the current or expected need for systemic corticosteroid therapy;

6. pregnant or lactating women.

7. Other psychological conditions that prevent patients from participating in the study or signing informed consent;

8. According to the investigator 's judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or fail to meet the requirements for participation in the study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The First Affiliated Hospital of Soochow University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

the First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

Countries

China

Other Identifiers

GZL

Identifier Type: -

Identifier Source: org_study_id