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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Large B-cell Lymphoma
• Intervention / Treatment: Biological: CNCT19; Drug: Gemcitabine Injection; Drug: busulfan; Drug: Melphalan Injection

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 Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Wei Liu, Dr.; Phone Number: 086-022-23909282; Email: liuwei@ihcams.ac.cn

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Institute of Hematology & Blood Diseases Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. 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

2. 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
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

4. Adequate bone marrow function as evidenced by:

   • Absolute neutrophil count (ANC) ≥ 1000/uL
   • Platelet count≥ 75,000/uL

5. 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
6. Cardiac ejection fraction ≥ 50%
7. Baseline oxygen saturation > 92% on room air
8. Life expectancy ≥3 months

Key Exclusion Criteria:

1. Active Central Nervous System (CNS) involvement by lymphoma
2. History of autologous or allogeneic stem cell transplantation
3. 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.
4. Presence of uncontrolled infection, cardio-cerebrovascular disease，coagulopathy, or connective tissue disease.
5. History of seizure or other CNS disorder
6. History of HIV infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Other Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Zou Dehui
• Collaborators: Juventas Cell Therapy Ltd.
• Investigators: Principal Investigator: Dehui Zou, Dr., Institute of Hematology & Blood Diseases Hospital, CAMS & PUMC

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Actual): December 30, 2023
• Study Completion (Estimated): December 30, 2024

Study Registration Dates

• First Submitted: December 26, 2020
• First Submitted That Met QC Criteria: December 26, 2020
• First Posted (Actual): December 30, 2020

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 14, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: large B-cell lymphoma; autologous stem-cell transplantation; anti-CD19 CAR T-cell
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Melphalan; Busulfan; Gemcitabine
• Other Study ID Numbers: IHBDH-IIT002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD that underlie results in a publication
• IPD Sharing Time Frame: The data from this study can be accessed for up to two years, starting two years after the completion of the research.
• IPD Sharing Access Criteria: The IPD are available from the principle investigator on reasonable request.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No