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

Institute of Hematology & Blood Diseases Hospital, China

Status and phase: Completed; Phase 2; Phase 1

Conditions: Large B-cell Lymphoma

Treatments: Biological: CNCT19; Drug: Gemcitabine Injection; Drug: Melphalan Injection; Drug: busulfan

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04690192

IIT2020013

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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30 participants in 1 patient group

CNCT19 following ASCT

Experimental group

Description:

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.

Treatment:

Drug: busulfan

Drug: Melphalan Injection

Drug: Gemcitabine Injection

Biological: CNCT19