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Clinical Study of XPO-1 Inhibitors Plus CAR-T Cells in Relapsed Refractory B-cell Non-Hodgkin's Lymphoma

Primary Purpose

Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma

Status

Recruiting

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Selinexor

Flu

CTX

CAR-T

About this trial

This is an interventional treatment trial for Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma focused on measuring XPO-1 Inhibitor, CAR-T Cells, Relapsed Refractory B-cell Non-Hodgkin's Lymphoma

Eligibility Criteria

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

Inclusion Criteria:

Age ≥ 18 years.
Pathological immunohistochemistry or flow cytometry confirmed that R/ R B-cell Non-Hodgkin's Lymphoma with measurable (diameter greater than 1.5cm) lesions meets any of the following conditions: 1> After 4 courses of standard first-line therapy or 2 courses of more than two-line therapy, the lesions were reduced by <50%; 2> R/ R B-cell Non-Hodgkin's Lymphoma with disease progression after first-line or induction therapy; 3> After hematopoietic stem cell transplantation, new lesions appear or the size of previously affected lesions increased by more than 50%.
Previously treated with 2 or more lines of therapy.
ECOG≤2#.
The main organ functions need to meet the following conditions:LVEF≥50%;CR≤132 umol/l or CCr≥60 ml/min; ALT and AST≤2.5 times normal range#TB≤2 times ULN#Lung function≤Level 1; dyspnea(CTCAE v5.0),and blood oxygen saturation without oxygen absorption> 90%.
Pass the T-cell amplification test.
Voluntary tissue puncture/biopsy for tumor tissue retrieval before and after treatment.
Subjects of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study until the follow-up one year period of the study.
Estimated survival time ≥3 months.
Voluntary signing of informed consent and good compliance.

Exclusion Criteria:

Have used immunosuppressants or hormones within 2 weeks prior to signing informed consent, or plan to have to use immunosuppressants or high-dose hormones (e.g. prednisone >15mg) after signing informed consent, specifically systemic treatment, excluding treatment with topical or inhaled corticosteroids.
The presence of bacterial, fungal, viral, mycoplasma or other types of infection that, in the judgment of the investigator, are difficult to control.
Active hepatitis B or active hepatitis C.
HIV infection.
Active acute or chronic graft-versus-host disease (GVHD) at the time of signing the informed consent form.
Participated in an investigational clinical trial of any other drug within 30 days prior to signing the informed consent form.
Received CAR-T cell therapy within 3 months prior to signing the informed consent form.
Received an allogeneic hematopoietic stem cell transplant within 6 months prior to signing the informed consent form.
Presence of contraindications to XPO-1 inhibitor.
Prior malignancy (other than Relapsed Refractory B-cell Non-Hodgkin's Lymphoma), except for cured malignant tumors with no active lesions for 3 years;Adequate treatment of inactive lesions in non-melanoma skin cancer,malignant tonsilloma or carcinoma in situ.
Pregnant or breasting-feeding women.
Conditions deemed by the researcher to be inappropriate for participation in this clinical trial.

Sites / Locations

The First Affiliated Hospital of Soochow UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

XPO-1 Inhibitor+CAR-T Cells

Arm Description

XPO-1 Inhibitor plus CAR-T Cells

Outcomes

Primary Outcome Measures

Overall Response Rate (ORR)

To measure the duration of response to XPO-1 Inhibitor Plus CAR-T Cells over a follow-up period of 12 months

Duration of Response(DOR) Duration of Response(DOR)

Duration of overall response will be assessed from the first XPO-1 Inhibitor Plus CAR-T cells given to progression,death or last follow-up.

Adverse events profile

Number of participants with adverse events. Frequencies of toxicities based on the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 will be tabulated.

Secondary Outcome Measures

Complete Response Rate

Number of patients who achieved complete response after treatment by XPO-1 Inhibitor plus CAR-T cells.

Progression-free Survival

To measure the duration of response to XPO-1 Inhibitor plus CAR-T cells over a follow-up period of 12 months.

Overall Survival

OS will be assessed from the first XPO-1 Inhibitor plus CAR-T cells given to death or last follow-up.

Peak Plasma Concentration

the peak amplification of CART in peripheral blood.

Time to Peak Amplification

The time to peak amplification of CART in peripheral blood.

AUC0-28

The area under the curve (AUC0-28) obtained by plotting the number of CAR-T cells in serum against the visit time from 0 to 28 days after reinfusion.

Full Information

NCT ID

NCT05322330

First Posted

March 21, 2022

Last Updated

February 7, 2023

Sponsor

The First Affiliated Hospital of Soochow University

Collaborators

West China Hospital, The General Hospital of Western Theater Command PLA, The Affiliated People's Hospital of Ningbo University Ningbo Yinzhou People's Hospital Community, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, Yixing People's Hospital, Affiliated Hospital of Jiangnan University, Wuxi Second People's Hospital

1. Study Identification

Unique Protocol Identification Number

NCT05322330

Brief Title

Clinical Study of XPO-1 Inhibitors Plus CAR-T Cells in Relapsed Refractory B-cell Non-Hodgkin's Lymphoma

Official Title

Clinical Study of the Efficacy and Safety of XPO-1 Inhibitors in Combination With CAR-T Cells in Relapsed Refractory B-cell Non-Hodgkin's Lymphoma

Study Type

Interventional

2. Study Status

Record Verification Date

March 2022

Overall Recruitment Status

Recruiting

Study Start Date

February 10, 2022 (Actual)

Primary Completion Date

February 10, 2024 (Anticipated)

Study Completion Date

February 10, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

The First Affiliated Hospital of Soochow University

Collaborators

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

Aim of this study will evaluate the Efficacy and Safety of XPO-1 inhibitors in combination with CAR-T cells in relapsed refractory B-cell non-Hodgkin's lymphoma

Detailed Description

B-cell non-Hodgkin's lymphoma (B-NHL) is the most common hematological malignancy originating from lymphohematopoietic tissue. Lymphoma is now one of the most rapidly growing malignancies worldwide, with approximately 350,000 new cases and over 200,000 deaths worldwide each year.With the use of rituximab in combination with standard chemotherapy regimens, progression-free survival (PFS) and overall survival (OS) in B-NHL have improved significantly, yet primary resistance or relapse progression still occurs in 40%-50% of B-NHL patients.The most widely used CAR-T therapy for R/R B-NHL in clinical practice is CAR-T therapy targeting CD19, which has a complete remission rate (CR) of 40%-53% and an overall remission rate (ORR) of 52%-82%.XPO1 inhibitors are potential drugs to enhance the anti-lymphoma effect of CD19 CAR-T cells, this study will evaluate the efficacy and safety of XPO-1 inhibitors in combination with CAR-T cells in relapsed refractory B-cell non-Hodgkin's lymphoma.

6. Conditions and Keywords

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

Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma

Keywords

XPO-1 Inhibitor, CAR-T Cells, Relapsed Refractory B-cell Non-Hodgkin's Lymphoma

7. Study Design

Primary Purpose

Treatment

Study Phase

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

XPO-1 Inhibitor+CAR-T Cells

Arm Type

Experimental

Arm Description

XPO-1 Inhibitor plus CAR-T Cells

Intervention Type

Drug

Intervention Name(s)

Selinexor

Other Intervention Name(s)

XPO-1 Inhibitor

Intervention Description

40-60mg QW,w-3～d-3,PO

Intervention Type

Drug

Intervention Name(s)

Flu

Other Intervention Name(s)

Fludarabine

Intervention Description

25-30 mg/m2，d-5 ～d-3，qd，ivgtt

Intervention Type

Drug

Intervention Name(s)

CTX

Other Intervention Name(s)

Cyclophosphamide

Intervention Description

250-500 mg/m2，d-5 ～d-3，qd，ivgtt

Intervention Type

Drug

Intervention Name(s)

CAR-T

Other Intervention Name(s)

Chimeric antigen receptor-modified T (CAR-T) cell therapy

Intervention Description

2-5×10^6 CAR-T/kg，ivgtt。

Primary Outcome Measure Information:

Title

Overall Response Rate (ORR)

Description

To measure the duration of response to XPO-1 Inhibitor Plus CAR-T Cells over a follow-up period of 12 months

Time Frame

up to 12 months

Title

Duration of Response(DOR) Duration of Response(DOR)

Description

Duration of overall response will be assessed from the first XPO-1 Inhibitor Plus CAR-T cells given to progression,death or last follow-up.

Time Frame

up to 12 months

Title

Adverse events profile

Description

Number of participants with adverse events. Frequencies of toxicities based on the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 will be tabulated.

Time Frame

up to 12 months

Secondary Outcome Measure Information:

Title

Complete Response Rate

Description

Number of patients who achieved complete response after treatment by XPO-1 Inhibitor plus CAR-T cells.

Time Frame

up to 12 months

Title

Progression-free Survival

Description

To measure the duration of response to XPO-1 Inhibitor plus CAR-T cells over a follow-up period of 12 months.

Time Frame

up to 12 months

Title

Overall Survival

Description

OS will be assessed from the first XPO-1 Inhibitor plus CAR-T cells given to death or last follow-up.

Time Frame

up to 12 months

Title

Peak Plasma Concentration

Description

the peak amplification of CART in peripheral blood.

Time Frame

Measured from start of treatment until 28 days after last dose

Title

Time to Peak Amplification

Description

The time to peak amplification of CART in peripheral blood.

Time Frame

Measured from start of treatment until 28 days after last dose

Title

AUC0-28

Description

The area under the curve (AUC0-28) obtained by plotting the number of CAR-T cells in serum against the visit time from 0 to 28 days after reinfusion.

Time Frame

Measured from start of treatment until 28 days after last dose

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age ≥ 18 years. Pathological immunohistochemistry or flow cytometry confirmed that R/ R B-cell Non-Hodgkin's Lymphoma with measurable (diameter greater than 1.5cm) lesions meets any of the following conditions: 1> After 4 courses of standard first-line therapy or 2 courses of more than two-line therapy, the lesions were reduced by <50%; 2> R/ R B-cell Non-Hodgkin's Lymphoma with disease progression after first-line or induction therapy; 3> After hematopoietic stem cell transplantation, new lesions appear or the size of previously affected lesions increased by more than 50%. Previously treated with 2 or more lines of therapy. ECOG≤2#. The main organ functions need to meet the following conditions:LVEF≥50%;CR≤132 umol/l or CCr≥60 ml/min; ALT and AST≤2.5 times normal range#TB≤2 times ULN#Lung function≤Level 1; dyspnea(CTCAE v5.0),and blood oxygen saturation without oxygen absorption> 90%. Pass the T-cell amplification test. Voluntary tissue puncture/biopsy for tumor tissue retrieval before and after treatment. Subjects of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study until the follow-up one year period of the study. Estimated survival time ≥3 months. Voluntary signing of informed consent and good compliance. Exclusion Criteria: Have used immunosuppressants or hormones within 2 weeks prior to signing informed consent, or plan to have to use immunosuppressants or high-dose hormones (e.g. prednisone >15mg) after signing informed consent, specifically systemic treatment, excluding treatment with topical or inhaled corticosteroids. The presence of bacterial, fungal, viral, mycoplasma or other types of infection that, in the judgment of the investigator, are difficult to control. Active hepatitis B or active hepatitis C. HIV infection. Active acute or chronic graft-versus-host disease (GVHD) at the time of signing the informed consent form. Participated in an investigational clinical trial of any other drug within 30 days prior to signing the informed consent form. Received CAR-T cell therapy within 3 months prior to signing the informed consent form. Received an allogeneic hematopoietic stem cell transplant within 6 months prior to signing the informed consent form. Presence of contraindications to XPO-1 inhibitor. Prior malignancy (other than Relapsed Refractory B-cell Non-Hodgkin's Lymphoma), except for cured malignant tumors with no active lesions for 3 years;Adequate treatment of inactive lesions in non-melanoma skin cancer,malignant tonsilloma or carcinoma in situ. Pregnant or breasting-feeding women. Conditions deemed by the researcher to be inappropriate for participation in this clinical trial.

Central Contact Person:

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

Caixia Li, M.D

Phone

+86 512 67781856

licaixia@suda.edu.cn

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Depei Wu, M.D

Organizational Affiliation

The First Affiliated Hospital of Soochow University

Official's Role

Study Chair

Facility Information:

Facility Name

The First Affiliated Hospital of Soochow University

City

Suzhou

State/Province

Jiangsu

ZIP/Postal Code

215000

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Caixia Li, M.D

Phone

+86 512 67781856

licaixia@suda.edu.cn

12. IPD Sharing Statement

Learn more about this trial

Clinical Study of XPO-1 Inhibitors Plus CAR-T Cells in Relapsed Refractory B-cell Non-Hodgkin's Lymphoma

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