Interleukin-7 and Chemokine (C-C Motif) Ligand 19-expressing CD19-CAR-T for Refractory/Relapsed B Cell Lymphoma.

Wenbin Qian

Status and phase: Unknown; Phase 2

Conditions: B Cell Lymphoma

Treatments: Biological: Interleukin-7 and Chemokine (C-C Motif) Ligand 19-expressing CD19-CAR-T cells

Study type: Interventional

Funder types: Other

Identifiers

NCT03929107

lymphoma center Q003

Details and patient eligibility

About

It's a single arm, open label prospective study, in which the safety and efficacy of Interleukin-7 and Chemokine (C-C Motif) Ligand 19-expressing CD19-CAR-T therapy are evaluated in refractory/relapsed B cell lymphoma patients.

Enrollment: 80 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 1. Age 18-75 years old, male or female;
• 2. ECOG 0-3, for patients with ECOG=4, if ECOG reach 0-3 after bridging treatment with ibrutinib, they are also considered to fit this criteria;
• 3. Histologically diagnosed as B cell non-Hodgkin's lymphoma (NHL)(according to WHO 2008 criteria), including DLBCL-NOS, primary mediastinal B cell lymphoma (PMBCL) mantel cell lymphoma (MCL), transformed follicular lymphoma (TFL) and other transformed B cell NHL;
• 4. CD19 positive (by immuno-histology or flowcytometry) [for DLBCL/PMBCL/TFL patients, negative CD19 immuno-histology results also acceptable];

• 5. Definition of relapsed and refractory disease: 1) refractory DLBCL should fit one of the following: ①complete remission NOT achieved after 2nd line treatment; ②progression of disease during treatment; ③duration of stable disease <6 months; ④ disease progress or relapse within 12 months of autologous stem cell transplantation.

  2. definition of refractory/relapsed disease for CLL and other indolent B cell NHL, should fit one of the following: ① failed or relapsed after 2nd therapy (Rituximab must be included) and being unable to accept ibrutinib treatment due to various reasons; ② non-responsive or intolerable to ibrutinib as 2nd line treatment; 3) refractory or relapsed MCL should fit one of the following: ① complete remission not achieved after 2nd line treatment; ② disease progression during treatment; ③duration of stable disease ≤6 months; ④disease progress or relapse within 12 months of autologous stem cell transplantation.
• 6. Previous treatment of aggressive B lymphomas must include Rituximab and anthracyclines;
• 7. Patients should have at least one measurable disease focus, with the longitudinal diameter ≥1.5cm, or any extra-nodal focus with the longitudinal diameter ≥1.0cm, with PET/CT positive results;
• 8. Blood routine test, absolute neutrophil count≥1000/ul、platelet count≥45000/ul；
• 9. Cardiac, hepatic and renal function: Creatinin <1.5 times of normal maximum；ALT/AST level <2.5 times of the maximum of normal range; total bilirubin<1.5 times of ULN；cardiac ejection fraction≥ 50%;
• 10. Patients should have the ability to fully understand contents of the written consent and be willing to sign the written consent;
• 11. Fertile patients should agree to take contraceptive measures during the process of this trial.

Exclusion criteria

• 1. History of other malignant tumor;
• 2. History of autologous stem cell transplantation within 6 weeks prior to enrollment;
• 3. Received CAR-T therapy within 3 months prior to enrollment;
• 4. Received cytotoxic medicine or glucocorticoids or other targeted-therapy medicine (except for ibrutinib) within 2 weeks prior to T cell collection;
• 5. With active autoimmune disease;
• 6. With active infection;
• 7. With HIV infection, or uncontrolled HBV/HCV/syphilis infection;
• 8. With known central nervous system lymphoma.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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80 participants in 1 patient group

Intervention group

Experimental group

Description:

In this group, patients will be treated with Interleukin-7 and Chemokine (C-C Motif) Ligand 19-expressing CD19-CAR-T, and the safety and efficacy will be evaluated.

Treatment:

Biological: Interleukin-7 and Chemokine (C-C Motif) Ligand 19-expressing CD19-CAR-T cells