A Phase 2 Study of CRG-022 in Patients With Relapsed/Refractory Large B-cell Lymphoma

Study Overview
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Brief Summary
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This is a prospective, open-label, multi-center clinical study designed to evaluate the safety, tolerability, efficacy, pharmacokinetics, pharmacodynamics, and immunogenicity of CRG-022, a CD22-directed autologous Chimeric Antigen Receptor (CAR) T-cell therapy for the treatment of relapsed or refractory large B-cell lymphoma (LBCL).

Detailed Description
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CRG-022 is an autologous CAR T-cell therapy targeting CD22, a common B-cell antigen widely expressed in LBCL. This Phase 2 study is designed to evaluate the safety and the efficacy of CRG-022 in patients with R/R LBCL that has progressed after CD19-directed CAR T-cell therapy. The study is designed to treat up to 123 patients with a single infusion of CRG-022.

Official Title
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An Open-label, Multicenter Phase 2 Study Evaluating the Efficacy and Safety of CRG-022, a CD22-directed Autologous Chimeric Antigen Receptor (CAR) T-cell Therapy in Patients With Relapsed/Refractory Large B-Cell Lymphoma After CD19-directed CAR T-cell Therapy

Conditions
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Cancer, Relapsed/Refractory Large B-cell Lymphoma (LBCL)

Intervention / Treatment
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* Drug: Fludarabine (Conditional therapy)
* Drug: Cyclophosphamide Monohydrate (Conditional therapy)
* Drug: CRG-022 cells (Experimental drug)


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Aged ≥18 years Relapsed or refractory large B-cell lymphoma. For enrollment in cohort 1, patients must have previously received a CD19-directed CAR T-cell therapy Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Adequate hematological, renal, and liver function Key Exclusion Criteria: Clinically significant concurrent medical illness Active infection requiring systemic antibiotics Prior allogeneic stem cell transplant or allogeneic cell therapy Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Drug<br>Single infusion of CRG-022 following conditioning chemotherapy | Drug: Fludarabine (Conditional therapy)<br>* Lymphodepletion chemotherapy<br>Drug: Cyclophosphamide Monohydrate (Conditional therapy)<br>* Lymphodepletion chemotherapy<br>Drug: CRG-022 cells (Experimental drug)<br>* Investigational agent<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate - Blinded independent review | Percentage of patients with complete or partial response determined by a blinded independent review committee | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate - Investigator assessment | Percentage of patients with complete or partial response determined by the investigator | Up to 24-months | 
| Complete response rate | Percentage of patients who achieve a Complete Response determined by independent review committee and investigators assessment | Up to 24-months | 
| Duration of response | Duration of response (the time from the date of the first occurrence of complete response or partial response to the date of progression, relapse, or death from any cause) determined by independent review committee and investigators | Up to 24-months | 
| Duration of complete response | Time from the date of the first occurrence of CR to the date of progression, relapse, or death from any cause determined by independent review committee and investigators. | Up to 24-months | 
| Progression-free survival | Progression-free survival (the time from CRG-022 infusion until the first occurrence of disease progression or relapse) determined by independent review committee and investigator assessment | Up to 24-months | 
| Overall Survival | Overall Survival (the period from the date of CRG-022 infusion until the date of death from any cause) documented by the Investigator. | Up to 24-months | 
| Incidence rate of adverse events | Percentage of patients with treatment-related adverse events is assessed by CTCAEv5.0, CRS, ICANS, and IEC-HS graded by ASTCT criteria. | From Screening up to 15 years at protocol-defined timepoints | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lymphoma, CD-22 Expressing Tumor, Chimeric Antigen Receptor, Adoptive Immunotherapy, Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Primary Mediastinal B-cell, Lymphoma, Transformed, Lymphoma, Transformed Non-Hodgkin, Lymphoma, Non-Hodgkin, CAR T, CAR T-cell therapy, Cell Therapy, Cellular Immuno-therapy, CRG-022, CD22