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

Status

Indicates the current recruitment status or the expanded access status.
Enrolling by invitation

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
20

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2022

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 30, 2024

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 22, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 22, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 4, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 4, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 22, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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