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

NCT ID: NCT04690192

Last Updated: 2025-05-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-01
• Study Completion Date: 2024-12-30

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.

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.

Conditions

Large B-cell Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

CNCT19

Intervention Type: BIOLOGICAL

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

Gemcitabine Injection

Intervention Type: DRUG

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

busulfan

Intervention Type: DRUG

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

Melphalan Injection

Intervention Type: DRUG

60mg/m2, day -3, -2

Interventions

CNCT19

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

Intervention Type: BIOLOGICAL

Gemcitabine Injection

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

Intervention Type: DRUG

busulfan

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

Intervention Type: DRUG

Melphalan Injection

60mg/m2, day -3, -2

Intervention Type: DRUG

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Juventas Cell Therapy Ltd.

INDUSTRY

Sponsor Role: collaborator

Institute of Hematology & Blood Diseases Hospital, China

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dehui Zou, Dr.

Role: PRINCIPAL_INVESTIGATOR

Institute of Hematology & Blood Diseases Hospital, CAMS & PUMC

Locations

Institute of Hematology & Blood Diseases Hospital

Tianjin, Tianjin Municipality, China

Countries

China

References

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.

Reference Type: DERIVED

PMID: 38631712 (View on PubMed)

Other Identifiers

IIT2020013

Identifier Type: -

Identifier Source: org_study_id