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

Primary Purpose

Large B-cell Lymphoma

Status

Recruiting

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

CNCT19

Gemcitabine Injection

busulfan

Melphalan Injection

About this trial

This is an interventional treatment trial for Large B-cell Lymphoma focused on measuring autologous stem-cell transplantation, anti-CD19 CAR T-cell, large B-cell lymphoma

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

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
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
Cardiac ejection fraction ≥ 50%
Baseline oxygen saturation > 92% on room air
Life expectancy ≥3 months

Key Exclusion Criteria:

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

Sites / Locations

Institute of Hematology & Blood Diseases HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CNCT19 following ASCT

Arm 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.

Outcomes

Primary Outcome Measures

Percentage of participants experiencing adverse events

Secondary Outcome Measures

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.

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.

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.

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.

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.

Overall Survival (OS)

OS is defined as the time from CNCT19 infusion to the date of death from any cause.

Full Information

NCT ID

NCT04690192

First Posted

December 26, 2020

Last Updated

June 30, 2023

Sponsor

Zou Dehui

Collaborators

Juventas Cell Therapy Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT04690192

Brief Title

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

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Recruiting

Study Start Date

January 1, 2021 (Actual)

Primary Completion Date

December 30, 2023 (Anticipated)

Study Completion Date

December 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Zou Dehui

Collaborators

Juventas Cell Therapy Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Large B-cell Lymphoma

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

CNCT19 following ASCT

Arm Type

Experimental

Arm 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.

Intervention Type

Biological

Intervention Name(s)

CNCT19

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Gemcitabine Injection

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

busulfan

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Melphalan Injection

Intervention Description

60mg/m2, day -3, -2

Primary Outcome Measure Information:

Title

Percentage of participants experiencing adverse events

Time Frame

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

Secondary Outcome Measure Information:

Title

Complete Response (CR) Rate

Description

Complete Response rate is defined as the incidence of a CR per the Lugano Classification (Cheson et al, 2014), as determined by study investigators.

Time Frame

2 years post CNCT19 infusion

Title

Objective Response Rate (ORR)

Description

ORR is defined as the incidence of either a CR or a partial response (PR) per the Lugano Classification as determined by study investigators.

Time Frame

2 years post CNCT19 infusion

Title

Progression-Free Survival (PFS)

Description

PFS is defined as the time from the CNCT19 infusion date to the date of disease progression or death from any cause.

Time Frame

2 years post CNCT19 infusion

Title

Duration of Response (DOR)

Description

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.

Time Frame

2 years post CNCT19 infusion

Title

Disease-Free Survival (DFS)

Description

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.

Time Frame

2 years post CNCT19 infusion

Title

Overall Survival (OS)

Description

OS is defined as the time from CNCT19 infusion to the date of death from any cause.

Time Frame

2 years post CNCT19 infusion

Other Pre-specified Outcome Measures:

Title

Levels of CNCT19 in blood

Time Frame

2 years post CNCT19 infusion

Title

Levels of cytokines in serum

Time Frame

1 month post CNCT19 infusion

Title

Levels of lymphocyte subsets in blood

Time Frame

1 year post CNCT19 infusion

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Key Inclusion Criteria: 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 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 Cardiac ejection fraction ≥ 50% Baseline oxygen saturation > 92% on room air Life expectancy ≥3 months Key Exclusion Criteria: 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Wei Liu, Dr.

Phone

086-022-23909282

liuwei@ihcams.ac.cn

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Dehui Zou, Dr.

Organizational Affiliation

Institute of Hematology & Blood Diseases Hospital, CAMS & PUMC

Official's Role

Principal Investigator

Facility Information:

Facility Name

Institute of Hematology & Blood Diseases Hospital

City

Tianjin

State/Province

Tianjin

ZIP/Postal Code

300020

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Wei Liu, Dr.

Phone

086-022-23909282

liuwei@ihcams.ac.cn

First Name & Middle Initial & Last Name & Degree

Dehui Zou, Dr.

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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