CNCT19 Following ASCT in Patients With Relapsed or Refractory B-cell Lymphoma

Study Overview
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Brief Summary
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The primary objective of this study is to explore the safety and efficacy of CNCT19 (a second-generation anti-CD19 CAR T-cell using 4-1BB as co-stimulatory domain provided by Juventas, Tianjin, China) infusion following ASCT in patients with relapsed or refractory B-cell lymphoma.

Detailed Description
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This is a single-center, non-randomized, open-label, prospective clinical trial to evaluate the safety and efficacy of CNCT19 infusion following high-dose chemotherapy and autologous stem-cell transplantation (HDT/ASCT) in patients with relapsed or refractory B-cell lymphoma. CNCT19 cells will be infused on day +3 (±1d) with a fixed dose of 2×10^6/kg. The study will assess the safety and efficacy of this combinational therapy, including the incidence and severity of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), hematological, and other non-hematological toxicities, and objective response rates and complete response rates and survivals of the subjects.

Official Title
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CNCT19 Following Autologous Stem Cell Transplantation in Patients With Relapsed or Refractory Aggressive B-cell Lymphoma

Conditions
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Large B-cell Lymphoma

Intervention / Treatment
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* Biological: CNCT19
* Drug: Gemcitabine Injection
* Drug: busulfan
* Drug: Melphalan Injection


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Histologically confirmed large B-cell lymphoma including the following types diffuse large B-cell lymphoma high-grade B-cell lymphoma with or without MYC and BLC2 and/or BCL6 rearrangement transformed lymphoma Relapsed or refractory diseases fulfilling one of the following criteria (individuals must have received anti-CD20 monoclonal antibody and anthracycline-containing chemotherapy regimen) Primary refractory disease, defined as disease progression after first-line immunochemotherapy or disease progression within 6 weeks of the end of the last chemotherapy Stable disease (SD) as best response after at least 4 cycles of first-line therapy Partial response (PR) as best response after at least 6 cycles of first-line therapy (biopsy-proven residual disease is needed for individuals with Deauville score of 4) PR as best response after at least 2 cycles of second-line therapy Disease relapse ≤12 months after the completion of first-line immunochemotherapy Relapsed or refractory disease after ≥2 lines of chemotherapy Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Adequate bone marrow function as evidenced by: Absolute neutrophil count (ANC) ≥ 1000/uL Platelet count≥ 75,000/uL Adequate renal and hepatic function defined as: Serum alanine aminotransferase (ALT/AST) ≤ 3 upper limit of normal (ULN) Total bilirubin ≤1.5 mg/dL, except in individuals with Gilbert's syndrome Serum creatinine ≤2 ULN, or creatinine clearance (as estimated by Cockcroft Gault) ≥ 40 mL/min Cardiac ejection fraction ≥ 50% Baseline oxygen saturation > 92% on room air Life expectancy ≥3 months Key Exclusion Criteria: Active Central Nervous System (CNS) involvement by lymphoma History of autologous or allogeneic stem cell transplantation Active HBV or HCV infection, defined as HBV-DNA or HCV-DNA levels above the normal upper limit, with or without abnormal liver function. Individuals with positive HBsAg or HBcAb should receive antiviral prophylaxis for at least 12 months after CNCT19 infusion. Presence of uncontrolled infection, cardio-cerebrovascular disease，coagulopathy, or connective tissue disease. History of seizure or other CNS disorder History of HIV infection

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: CNCT19 following ASCT<br>Participants will receive high-dose chemotherapy followed by stem-cell reinfusion, and a fixed dose of CNCT19 (2×10^6/kg) will be infused in a single-dose on day +2, +3 or +4. | Biological: CNCT19<br>* 2×10^6/kg, infused in a single-dose on day +2, +3 or +4 following stem-cell infusion<br>Drug: Gemcitabine Injection<br>* 600mg/m2/h, infused for 3 hours with loading bolus of 75mg/m2, day -7, -3,<br>Drug: busulfan<br>* 105mg/m2, day -7 until -5,<br>Drug: Melphalan Injection<br>* 60mg/m2, day -3, -2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants experiencing adverse events |  | from the first day of high-dose chemotherapy until 2 years post CNCT19 infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response (CR) Rate | Complete Response rate is defined as the incidence of a CR per the Lugano Classification (Cheson et al, 2014), as determined by study investigators. | 2 years post CNCT19 infusion | 
| Objective Response Rate (ORR) | ORR is defined as the incidence of either a CR or a partial response (PR) per the Lugano Classification as determined by study investigators. | 2 years post CNCT19 infusion | 
| Progression-Free Survival (PFS) | PFS is defined as the time from the CNCT19 infusion date to the date of disease progression or death from any cause. | 2 years post CNCT19 infusion | 
| Duration of Response (DOR) | DOR is defined only for participants who experience an objective response after CNCT19 infusion and is the time from the first objective response to disease progression or death from any cause. | 2 years post CNCT19 infusion | 
| Disease-Free Survival (DFS) | DFS is defined only for participants who achieve complete response after CNCT19 infusion and is the time from complete response to disease progression or death from any cause. | 2 years post CNCT19 infusion | 
| Overall Survival (OS) | OS is defined as the time from CNCT19 infusion to the date of death from any cause. | 2 years post CNCT19 infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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autologous stem-cell transplantation, anti-CD19 CAR T-cell, large B-cell lymphoma