Clinical trial NCT04690192: CNCT19 Following ASCT in Patients With Relapsed or Refractory B-cell Lymphoma
Official title: CNCT19 Following Autologous Stem Cell Transplantation in Patients With Relapsed or Refractory Aggressive B-cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Large B-cell Lymphoma
Keywords: autologous stem-cell transplantation
anti-CD19 CAR T-cell
large B-cell lymphoma
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
Collaborators: name: Juventas Cell Therapy Ltd.
First posted: 2020-12-30
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Percentage of participants experiencing adverse events
timeFrame: from the first day of high-dose chemotherapy until 2 years post CNCT19 infusion
Secondary outcomes:
measure: Complete Response (CR) Rate
timeFrame: 2 years post CNCT19 infusion
measure: Objective Response Rate (ORR)
timeFrame: 2 years post CNCT19 infusion
measure: Progression-Free Survival (PFS)
timeFrame: 2 years post CNCT19 infusion
measure: Duration of Response (DOR)
timeFrame: 2 years post CNCT19 infusion
measure: Disease-Free Survival (DFS)
timeFrame: 2 years post CNCT19 infusion
measure: Overall Survival (OS)
timeFrame: 2 years post CNCT19 infusion
Other outcomes:
measure: Levels of CNCT19 in blood
timeFrame: 2 years post CNCT19 infusion
measure: Levels of cytokines in serum
timeFrame: 1 month post CNCT19 infusion
measure: Levels of lymphocyte subsets in blood
timeFrame: 1 year post CNCT19 infusion
Locations:
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital
state: Tianjin
Study officials:
affiliation: Institute of Hematology & Blood Diseases Hospital, CAMS & PUMC
name: Dehui Zou, Dr.
role: PRINCIPAL_INVESTIGATOR
References: