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

March 22, 2023 updated by: The First Affiliated Hospital of Soochow University

Prospective, Single-center, Single-arm, Open-label Study of Obinutuzumab, Zanubrutinib and Lenalidomide Sequential CD19/CD22 CAR-T in Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

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.

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

20

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Jiangsu
      • Suzhou, Jiangsu, China, 215006
        • The First Affiliated Hospital of Soochow University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: Obinutuzumab
Obinutuzumab Injection 1000mg ivgtt C1-C4 d1；
Other Names:
  • Gazyva
Drug: Zanubrutinib
Zanubrutinib 160mg (2 capsules) oral bid；
Other Names:
  • Brukinsa
Drug: Lenalidomide
Lenalidomide 25mg (1 capsule) oral C1-C4 d1-d10.
Other Names:
  • Anxian
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.
Drug: Azacitidine For Injection
Azacitidine For Injection 100mg i.h. d1-d5;
Other Names:
  • Anyve
Drug: Fludarabine
Fludarabine 300mg/m2 ivgtt d3-d5;
Other Names:
  • Fludara
Drug: Cyclophosphamide
Cyclophosphamide 300mg/m2 ivgtt d3-d5.
Other Names:
  • Endoxan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall response rate (ORR) after GZL therapy
Time Frame: At the end of GZL therapy (2-4 cycles, each cycle is 21days)
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
Time Frame: Within 3 months after CAR-T therapy
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
Time Frame: up to 24 months after the end of last patient's treatment
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of treatment-emergent adverse events, treatment-related adverse events and serious adverse events
Time Frame: Initiation of GZL therapy until 30 days after CAR-T therapy
The safety and tolerability of the therapeutic regimen measured by the incidence of Treatment-Emergent Adverse Event.
Initiation of GZL therapy until 30 days after CAR-T therapy
Overall response rate (ORR) after CAR-T
Time Frame: Within 3 months after CAR-T therapy
The best rate of patients who achieved CR or PR after CAR-T therapy
Within 3 months after CAR-T therapy
Overall survival (OS) after CAR-T
Time Frame: up to 24 months after the end of last patient's treatment
OS will be assessed from the GZL combination therapy given to date of death or end of follow-up.
up to 24 months after the end of last patient's treatment
Duration of Response(DOR) after CAR-T
Time Frame: up to 24 months after the end of last patient's treatment
DOR will be assessed from the date of CAR-T infusion to the date of progression, relapse, death or end of follow-up
up to 24 months after the end of last patient's treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The First Affiliated Hospital of Soochow University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2022

Primary Completion (Anticipated)

June 30, 2024

Study Completion (Anticipated)

June 30, 2024

Study Registration Dates

First Submitted

March 22, 2023

First Submitted That Met QC Criteria

March 22, 2023

First Posted (Actual)

April 4, 2023

Study Record Updates

Last Update Posted (Actual)

April 4, 2023

Last Update Submitted That Met QC Criteria

March 22, 2023

Last Verified

February 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GZL

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All the data would be available at the First Affiliated Hospital and other researchers after the end of the study.

IPD Sharing Time Frame

after the end of the study

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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