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

NCT05322330 | Unknown Phase 2

• 1 other identifier: R/R B-NHL 01
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (3)

• 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

  up to 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.

  up to 12 months

• 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.

  up to 12 months

Secondary Outcomes (6)

• Complete Response Rate

  up to 12 months

• Progression-free Survival

  up to 12 months

• Overall Survival

  up to 12 months

• Peak Plasma Concentration

  Measured from start of treatment until 28 days after last dose

• Time to Peak Amplification

  Measured from start of treatment until 28 days after last dose

Study Arms (1)

XPO-1 Inhibitor+CAR-T Cells

EXPERIMENTAL

XPO-1 Inhibitor plus CAR-T Cells

Drug: Selinexor; Drug: Flu; Drug: CTX; Drug: CAR-T

Interventions

Selinexor DRUG

40-60mg QW,w-3～d-3,PO

Also known as: XPO-1 Inhibitor

XPO-1 Inhibitor+CAR-T Cells

Flu DRUG

25-30 mg/m2，d-5 ～d-3，qd，ivgtt

Also known as: Fludarabine

XPO-1 Inhibitor+CAR-T Cells

CTX DRUG

250-500 mg/m2，d-5 ～d-3，qd，ivgtt

Also known as: Cyclophosphamide

XPO-1 Inhibitor+CAR-T Cells

CAR-T DRUG

2-5×10\^6 CAR-T/kg，ivgtt。

Also known as: Chimeric antigen receptor-modified T (CAR-T) cell therapy

XPO-1 Inhibitor+CAR-T Cells

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• The First Affiliated Hospital of Soochow University: lead
• West China Hospital: collaborator
• The General Hospital of Western Theater Command: collaborator
• The Affiliated People's Hospital of Ningbo University Ningbo Yinzhou People's Hospital Community: collaborator
• The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School: collaborator
• Yixing People's Hospital: collaborator
• Affiliated Hospital of Jiangnan University: collaborator
• Wuxi No. 2 People's Hospital: collaborator

Study Sites (1)

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215000, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, B-Cell

Interventions

selinexor; Influenza Vaccines; fludarabine; Cyclophosphamide; Cell- and Tissue-Based Therapy

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Biological Therapy; Therapeutics

Study Officials

• Depei Wu, M.D

  The First Affiliated Hospital of Soochow University

  STUDY CHAIR

Central Study Contacts

Caixia Li, M.D

CONTACT

+86 512 67781856; licaixia@suda.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2022
• First Posted: April 11, 2022
• Study Start: February 10, 2022
• Primary Completion: February 10, 2024
• Study Completion: February 10, 2024
• Last Updated: February 9, 2023

Record last verified: 2022-03

Locations

CN (1)