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

NCT04690192 | Completed Phase 1

• 1 other identifier: IIT2020013
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Large B-cell Lymphoma

Keywords

autologous stem-cell transplantation; anti-CD19 CAR T-cell; large B-cell lymphoma

Outcome Measures

Primary Outcomes (1)

• Percentage of participants experiencing adverse events

  from the first day of high-dose chemotherapy until 2 years post CNCT19 infusion

Secondary Outcomes (6)

• Complete Response (CR) Rate

  2 years post CNCT19 infusion

• Objective Response Rate (ORR)

  2 years post CNCT19 infusion

• Progression-Free Survival (PFS)

  2 years post CNCT19 infusion

• Duration of Response (DOR)

  2 years post CNCT19 infusion

• Disease-Free Survival (DFS)

  2 years post CNCT19 infusion

Other Outcomes (3)

• 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

Study Arms (1)

CNCT19 following ASCT

EXPERIMENTAL

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; Drug: Gemcitabine Injection; Drug: busulfan; Drug: Melphalan Injection

Interventions

CNCT19 BIOLOGICAL

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

CNCT19 following ASCT

Gemcitabine Injection DRUG

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

CNCT19 following ASCT

busulfan DRUG

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

CNCT19 following ASCT

Melphalan Injection DRUG

60mg/m2, day -3, -2

CNCT19 following ASCT

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead
• Juventas Cell Therapy Ltd.: collaborator

Study Sites (1)

Institute of Hematology & Blood Diseases Hospital

Tianjin, Tianjin Municipality, 300020, China

Location

Related Publications (1)

• Liu W, Liu W, Zou H, Chen L, Huang W, Lv R, Xu Y, Liu H, Shi Y, Wang K, Wang Y, Xiong W, Deng S, Yi S, Sui W, Peng G, Ma Y, Wang H, Lv L, Wang J, Wei J, Qiu L, Zheng W, Zou D. Combinational therapy of CAR T-cell and HDT/ASCT demonstrates impressive clinical efficacy and improved CAR T-cell behavior in relapsed/refractory large B-cell lymphoma. J Immunother Cancer. 2024 Apr 16;12(4):e008857. doi: 10.1136/jitc-2024-008857.

  PMID: 38631712 DERIVED

MeSH Terms

Interventions

Gemcitabine; Busulfan; Melphalan

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Dehui Zou, Dr.

  Institute of Hematology & Blood Diseases Hospital, CAMS & PUMC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 26, 2020
• First Posted: December 30, 2020
• Study Start: January 1, 2021
• Primary Completion: December 30, 2023
• Study Completion: December 30, 2024
• Last Updated: May 13, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: The data from this study can be accessed for up to two years, starting two years after the completion of the research.
• Access Criteria: The IPD are available from the principle investigator on reasonable request.

Locations

CN (1)