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

NCT05797948 | Unknown

• 1 other identifier: GZL
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

Keywords

Humanized anti-CD20 monoclonal antibody; BTK Inhibitor; Immunomodulators; CAR-T

Outcome Measures

Primary Outcomes (3)

• Overall response rate (ORR) after GZL therapy

  the rate of patients who achieved CR or PR after GZL therapy

  At the end of GZL therapy (2-4 cycles, each cycle is 21days)

• Complete response rate (CRR) after CAR-T

  the best rate of patients who achieved CR after CAR-T therapy

  Within 3 months after CAR-T therapy

• Progression-free survival (PFS) after CAR-T

  PFS will be assessed from the GZL combination therapy given to date of progression, relapse, death or end of follow-up.

  up to 24 months after the end of last patient's treatment

Secondary Outcomes (4)

• Incidence of treatment-emergent adverse events, treatment-related adverse events and serious adverse events

  Initiation of GZL therapy until 30 days after CAR-T therapy

• Overall response rate (ORR) after CAR-T

  Within 3 months after CAR-T therapy

• Overall survival (OS) after CAR-T

  up to 24 months after the end of last patient's treatment

• Duration of Response(DOR) after CAR-T

  up to 24 months after the end of last patient's treatment

Study Arms (1)

GZL sequential CD19/CD22 CAR-T

EXPERIMENTAL

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.

Drug: Obinutuzumab; Drug: Zanubrutinib; Drug: Lenalidomide; Drug: CD19/CD22 CAR-T; Drug: Azacitidine For Injection; Drug: Fludarabine; Drug: Cyclophosphamide

Interventions

Obinutuzumab DRUG

Obinutuzumab Injection 1000mg ivgtt C1-C4 d1；

Also known as: Gazyva

GZL sequential CD19/CD22 CAR-T

Zanubrutinib DRUG

Zanubrutinib 160mg (2 capsules) oral bid；

Also known as: Brukinsa

GZL sequential CD19/CD22 CAR-T

Lenalidomide DRUG

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

Also known as: Anxian

GZL sequential CD19/CD22 CAR-T

CD19/CD22 CAR-T 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.

GZL sequential CD19/CD22 CAR-T

Azacitidine For Injection DRUG

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

Also known as: Anyve

GZL sequential CD19/CD22 CAR-T

Fludarabine DRUG

Fludarabine 300mg/m2 ivgtt d3-d5;

Also known as: Fludara

GZL sequential CD19/CD22 CAR-T

Cyclophosphamide DRUG

Cyclophosphamide 300mg/m2 ivgtt d3-d5.

Also known as: Endoxan

GZL sequential CD19/CD22 CAR-T

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Disease refractory to first-line therapy or early relapse within 12 months of last treatment.
• Relapse or progressive disease (PD) ≥ 3 months after targeted CD19 therapy including CD19 CAR T cells or anti-CD19/anti-CD3.
• Successful leukapheresis assessment and T-cell preculture.
• Life expectancy \> 3 months.
• 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.
• 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.
• Measurable or evaluable lesions according to "IWG response criteria for malignant lymphoma" (Cheson 2014).
• Patients have the ability to understand and are willing to provide written informed consent.

You may not qualify if:

• severe liver and kidney dysfunction (alanine aminotransferase, bilirubin, creatinine \> 3 times the upper limit of normal);
• the presence of structural heart disease, and lead to clinical symptoms or abnormal heart function (NYHA ≥ 2);
• uncontrolled active infection;
• the presence of other tumors requiring treatment or intervention;
• the current or expected need for systemic corticosteroid therapy;
• pregnant or lactating women.
• Other psychological conditions that prevent patients from participating in the study or signing informed consent;
• 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.

Sponsors & Collaborators

• The First Affiliated Hospital of Soochow University: lead

Study Sites (1)

the First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215006, China

Location

MeSH Terms

Conditions

Recurrence; Lymphoma, B-Cell

Interventions

obinutuzumab; zanubrutinib; Lenalidomide; Azacitidine; Injections; fludarabine; fludarabine phosphate; Cyclophosphamide

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Aza Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Drug Administration Routes; Drug Therapy; Therapeutics; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2023
• First Posted: April 4, 2023
• Study Start: July 1, 2022
• Primary Completion: June 30, 2024
• Study Completion: June 30, 2024
• Last Updated: April 4, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: after the end of the study

Locations

CN (1)