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Assessment of Safety and Efficacy of ThisCART19A in Adult Patients With B-NHL After Failure of Autologous Chimeric Antigen Receptor T- Cell(CAR-T) Therapy

Primary Purpose

Non-Hodgkin's Lymphoma

Status

Recruiting

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

ThisCART19A

About this trial

This is an interventional treatment trial for Non-Hodgkin's Lymphoma

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Cellular or histopathological diagnosis of B-cell non-Hodgkin's lymphoma (B-NHL) includes: diffuse Large B-cell lymphoma (DLBCL), follicular lymphoma to DLBCL (tFL), follicular lymphatic (FL), Mantle cell lymphoma (MCL), primary Mediastinal Large B-cell lymphoma (PMBCL), etc.
Failing to autologous CAR-T therapy.
At least one available lesion to be assessed.
Good organ function during screening.
Should be confirmed Cluster of differentiation(CD)19 positive by biopsy for the patient who received target CD19 therapy before.

Exclusion Criteria:

Allergic to preconditioning measures.
Patients with other malignancies other than B-cell malignancies within 5 years prior to screening. Patients with cured skin squamous carcinoma, basal carcinoma, non-primary invasive bladder cancer, localized low-risk prostate cancer, in situ cervical/breast cancer can be recruited.
Uncontrollable bacterial, fungal and viral infection during screening.
Patients had pulmonary embolism within 3 months prior to enrollment.
Had intolerant severe cardiovascular and cerebrovascular diseases and hereditary diseases prior to enrollment.
Imaging confirmed the presence of central nervous system involvement (both primary and secondary) and obvious symptoms at the time of screening.
Active hepatitis B virus (HBV) or hepatitis C virus (HCV) or Human immunodeficiency virus (HIV) or Syphilis infection. HBV-DNA < 2000 IU/mL can be enrolled, but should admitted to use anti-virus drugs such as entecavir, tenofovir, etc, and supervisory the relative indication during the treatment.
Had big lesion(single lesion diameter ≥10 cm).
Bone marrow involvement≥5%.
Receive allogeneic hematopoietic stem cell transplantation less than 100 days.
Combined systemic steroid use (e.g., prednisone ≥20mg) within 3 days prior to screening. Or systemic diseases that require long-term use of immunization Inhibitor.
Vaccinated with influenza vaccine within 2 weeks prior to lymphodepleting chemotherapy (Severe Acute Respiratory Syndrome-Corona virus disease 19 can be included, inactivated, live/non-live adjuvant vaccinations allowed to be included) .
Patients who are receiving Graft versus host disease Hepatitis(GvHD) treatment; Patients without GvHD and who had stopped immunosuppressive drugs for at least 1 month were eligible for inclusion.
Women who are in pregnant or lactating, and female subjects or partners who plan to be pregnant within 1 year after cell infusion. Male subjects who plan pregnancy within 1 year after infusion.

Sites / Locations

The first affiliated hospital of medical college of zhejiang universityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

ThisCART19A 2×10^6 cells/kg for dose level 1

ThisCART19A 3×10^6 cells/kg as dose level 2

Patients will receive 4×10^6 cells/kg as dose level 3

Arm Description

Patients will receive 2×10^6 cells/kg of ThisCART19A

Patients will receive 3×10^6 cells/kg of ThisCART19A

Patients will receive 4×10^6 cells/kg of ThisCART19A

Outcomes

Primary Outcome Measures

Dose limited toxicity(DLT) observation in patient with NHL during dose escalation stage

DLT is defined as the incidence of severe adverse events related to ThisCART19A more than 33% in each dose level.

Objective Response Rate in patient with NHL during dose expansion stage

the incidence of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or unevaluable (UE) as best response to treatment

Secondary Outcome Measures

Objective Response Rate during dose escalation stage and expansion stage

the incidence of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or unevaluable (UE) as best response to treatment

Duration of response(DOR) during dose escalation stage and expansion stage

The duration of overall response is measured from the time measurement criteria are met for complete response (CR) or partial response (PR)

OS(overall survival) during dose escalation stage and expansion stage

Overall survival (OS) is defined as the time from the date of lymphodepletion until death from any cause.

Time to remission(TTR) during dose escalation stage and expansion stage

Time to remission(TTR) is defined as the time from the date of ThisCART19A infusion until the date of first remission.

Analysis the change characteristics of CART cell number and copy number during dose escalation and expansion stages

Track CAR T cells expansion in patients after infusion

Analysis the change characteristics of cytokines and immune effect cells number during dose escalation and expansion stages

Analysis the effect cells and cytokines in patient after infusion

Analysis the severity and Incidence of Adverse Events in each dose level during dose expansion stage

Including more than or equal to grade 3 adverse events graded according to the NCI CTCAE v5.0, or the adverse events with special attention

Analysis the immunogenicity(anti-therapeutic antibody and neutralizing antibody) of CAR-T cells after infusion

Full Information

NCT ID

NCT05349266

First Posted

April 8, 2022

Last Updated

April 21, 2022

Sponsor

Zhejiang University

1. Study Identification

Unique Protocol Identification Number

NCT05349266

Brief Title

Assessment of Safety and Efficacy of ThisCART19A in Adult Patients With B-NHL After Failure of Autologous Chimeric Antigen Receptor T- Cell(CAR-T) Therapy

Official Title

Assessment of Safety and Efficacy of ThisCART19A in Adult Patients With B Cells Non-Hodgkin's Lymphoma(B-NHL) After Failure of Autologous CAR-T Therapy

Study Type

Interventional

2. Study Status

Record Verification Date

April 2022

Overall Recruitment Status

Recruiting

Study Start Date

March 18, 2022 (Actual)

Primary Completion Date

March 30, 2024 (Anticipated)

Study Completion Date

April 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Zhejiang University

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

This is a phase I, single center study to assess the efficacy and safety of ThisCART19A in adult with Non-Hodgkins Lymphoma in China.

6. Conditions and Keywords

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

Non-Hodgkin's Lymphoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

16 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

ThisCART19A 2×10^6 cells/kg for dose level 1

Arm Type

Experimental

Arm Description

Patients will receive 2×10^6 cells/kg of ThisCART19A

Arm Title

ThisCART19A 3×10^6 cells/kg as dose level 2

Arm Type

Experimental

Arm Description

Patients will receive 3×10^6 cells/kg of ThisCART19A

Arm Title

Patients will receive 4×10^6 cells/kg as dose level 3

Arm Type

Experimental

Arm Description

Patients will receive 4×10^6 cells/kg of ThisCART19A

Intervention Type

Biological

Intervention Name(s)

ThisCART19A

Intervention Description

each patient will receive a dose level per body weight(kg) for only once.

Primary Outcome Measure Information:

Title

Dose limited toxicity(DLT) observation in patient with NHL during dose escalation stage

Description

DLT is defined as the incidence of severe adverse events related to ThisCART19A more than 33% in each dose level.

Time Frame

28 days

Title

Objective Response Rate in patient with NHL during dose expansion stage

Description

the incidence of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or unevaluable (UE) as best response to treatment

Time Frame

12 months

Secondary Outcome Measure Information:

Title

Objective Response Rate during dose escalation stage and expansion stage

Description

the incidence of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or unevaluable (UE) as best response to treatment

Time Frame

12 months

Title

Duration of response(DOR) during dose escalation stage and expansion stage

Description

The duration of overall response is measured from the time measurement criteria are met for complete response (CR) or partial response (PR)

Time Frame

12 months

Title

OS(overall survival) during dose escalation stage and expansion stage

Description

Overall survival (OS) is defined as the time from the date of lymphodepletion until death from any cause.

Time Frame

12 months

Title

Time to remission(TTR) during dose escalation stage and expansion stage

Description

Time to remission(TTR) is defined as the time from the date of ThisCART19A infusion until the date of first remission.

Time Frame

12 months

Title

Analysis the change characteristics of CART cell number and copy number during dose escalation and expansion stages

Description

Track CAR T cells expansion in patients after infusion

Time Frame

6 months

Title

Analysis the change characteristics of cytokines and immune effect cells number during dose escalation and expansion stages

Description

Analysis the effect cells and cytokines in patient after infusion

Time Frame

3 months

Title

Analysis the severity and Incidence of Adverse Events in each dose level during dose expansion stage

Description

Including more than or equal to grade 3 adverse events graded according to the NCI CTCAE v5.0, or the adverse events with special attention

Time Frame

3 months

Title

Analysis the immunogenicity(anti-therapeutic antibody and neutralizing antibody) of CAR-T cells after infusion

Time Frame

12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Cellular or histopathological diagnosis of B-cell non-Hodgkin's lymphoma (B-NHL) includes: diffuse Large B-cell lymphoma (DLBCL), follicular lymphoma to DLBCL (tFL), follicular lymphatic (FL), Mantle cell lymphoma (MCL), primary Mediastinal Large B-cell lymphoma (PMBCL), etc. Failing to autologous CAR-T therapy. At least one available lesion to be assessed. Good organ function during screening. Should be confirmed Cluster of differentiation(CD)19 positive by biopsy for the patient who received target CD19 therapy before. Exclusion Criteria: Allergic to preconditioning measures. Patients with other malignancies other than B-cell malignancies within 5 years prior to screening. Patients with cured skin squamous carcinoma, basal carcinoma, non-primary invasive bladder cancer, localized low-risk prostate cancer, in situ cervical/breast cancer can be recruited. Uncontrollable bacterial, fungal and viral infection during screening. Patients had pulmonary embolism within 3 months prior to enrollment. Had intolerant severe cardiovascular and cerebrovascular diseases and hereditary diseases prior to enrollment. Imaging confirmed the presence of central nervous system involvement (both primary and secondary) and obvious symptoms at the time of screening. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) or Human immunodeficiency virus (HIV) or Syphilis infection. HBV-DNA < 2000 IU/mL can be enrolled, but should admitted to use anti-virus drugs such as entecavir, tenofovir, etc, and supervisory the relative indication during the treatment. Had big lesion(single lesion diameter ≥10 cm). Bone marrow involvement≥5%. Receive allogeneic hematopoietic stem cell transplantation less than 100 days. Combined systemic steroid use (e.g., prednisone ≥20mg) within 3 days prior to screening. Or systemic diseases that require long-term use of immunization Inhibitor. Vaccinated with influenza vaccine within 2 weeks prior to lymphodepleting chemotherapy (Severe Acute Respiratory Syndrome-Corona virus disease 19 can be included, inactivated, live/non-live adjuvant vaccinations allowed to be included) . Patients who are receiving Graft versus host disease Hepatitis(GvHD) treatment; Patients without GvHD and who had stopped immunosuppressive drugs for at least 1 month were eligible for inclusion. Women who are in pregnant or lactating, and female subjects or partners who plan to be pregnant within 1 year after cell infusion. Male subjects who plan pregnancy within 1 year after infusion.

Central Contact Person:

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

Ming Ming Zhang, Doctor

Phone

13656674208

mingmingzhang@zju.edu.cn

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

He Huang, Doctor

Organizational Affiliation

First hospital affiliated Zhejiang University

Official's Role

Principal Investigator

Facility Information:

Facility Name

The first affiliated hospital of medical college of zhejiang university

City

Hangzhou

State/Province

Zhejiang

ZIP/Postal Code

310003

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

He Huang, Doctor

Phone

86-13605714822

hehuangyu@126.com

12. IPD Sharing Statement

Learn more about this trial

Assessment of Safety and Efficacy of ThisCART19A in Adult Patients With B-NHL After Failure of Autologous Chimeric Antigen Receptor T- Cell(CAR-T) Therapy

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