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

Relapsed or Refractory B-cell Non-Hodgkin Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05797948
• Other study ID #: GZL
• Status: Enrolling by invitation
• Phase: N/A
• Start date: July 1, 2022
• Est. completion date: June 30, 2024

Study information

• Verified date: February 2023
• Source: The First Affiliated Hospital of Soochow University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 20
• Est. completion date: June 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin
• Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

Intervention

Drug:
• Obinutuzumab
Obinutuzumab Injection 1000mg ivgtt C1-C4 d1;
• Zanubrutinib
Zanubrutinib 160mg (2 capsules) oral bid;
• Lenalidomide
Lenalidomide 25mg (1 capsule) oral C1-C4 d1-d10.
• 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.
• Azacitidine For Injection
Azacitidine For Injection 100mg i.h. d1-d5;
• Fludarabine
Fludarabine 300mg/m2 ivgtt d3-d5;
• Cyclophosphamide
Cyclophosphamide 300mg/m2 ivgtt d3-d5.

Locations

Country	Name	City	State
China	the First Affiliated Hospital of Soochow University	Suzhou	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
The First Affiliated Hospital of Soochow University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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
Primary	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	Incidence of treatment-emergent adverse events, treatment-related adverse events and serious adverse events	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
Secondary	Overall response rate (ORR) after CAR-T	The best rate of patients who achieved CR or PR after CAR-T therapy	Within 3 months after CAR-T therapy
Secondary	Overall survival (OS) after CAR-T	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
Secondary	Duration of Response(DOR) after CAR-T	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