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

Sponsor

Zou Dehui (Other)

Overall Status

Recruiting

CT.gov ID

NCT04690192

Collaborator

Juventas Cell Therapy Ltd. (Industry)

Enrollment

Location

Arm

47.9

Anticipated Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Large B-cell Lymphoma	Biological: CNCT19 Drug: Gemcitabine Injection Drug: busulfan Drug: Melphalan Injection	Phase 1/Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jan 1, 2021

Anticipated Primary Completion Date :

Dec 30, 2022

Anticipated Study Completion Date :

Dec 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CNCT19 following ASCT 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 2×10^6/kg, infused in a single-dose on day +2, +3 or +4 following stem-cell infusion Drug: Gemcitabine Injection 600mg/m2/h, infused for 3 hours with loading bolus of 75mg/m2, day -7, -3, Drug: busulfan 105mg/m2, day -7 until -5, Drug: Melphalan Injection 60mg/m2, day -3, -2

Arm

Intervention/Treatment

Experimental: CNCT19 following ASCT

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

2×10^6/kg, infused in a single-dose on day +2, +3 or +4 following stem-cell infusion

Drug: Gemcitabine Injection

600mg/m2/h, infused for 3 hours with loading bolus of 75mg/m2, day -7, -3,

Drug: busulfan

105mg/m2, day -7 until -5,

Drug: Melphalan Injection

60mg/m2, day -3, -2

Outcome Measures

Primary Outcome Measures

Percentage of participants experiencing adverse events [from the first day of high-dose chemotherapy until 2 years post CNCT19 infusion]

Secondary Outcome Measures

Complete Response (CR) Rate [2 years post CNCT19 infusion]
Complete Response rate is defined as the incidence of a CR per the Lugano Classification (Cheson et al, 2014), as determined by study investigators.
Objective Response Rate (ORR) [2 years post CNCT19 infusion]
ORR is defined as the incidence of either a CR or a partial response (PR) per the Lugano Classification as determined by study investigators.
Progression-Free Survival (PFS) [2 years post CNCT19 infusion]
PFS is defined as the time from the CNCT19 infusion date to the date of disease progression or death from any cause.
Duration of Response (DOR) [2 years post CNCT19 infusion]
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.
Disease-Free Survival (DFS) [2 years post CNCT19 infusion]
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.
Overall Survival (OS) [2 years post CNCT19 infusion]
OS is defined as the time from CNCT19 infusion to the date of death from any cause.

Other Outcome Measures

Levels of CNCT19 in blood [2 years post CNCT19 infusion]
Levels of cytokines in serum [1 month post CNCT19 infusion]
Levels of lymphocyte subsets in blood [1 year post CNCT19 infusion]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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