Clinical trial NCT03929107: Interleukin-7 and Chemokine (C-C Motif) Ligand 19-expressing CD19-CAR-T for Refractory/Relapsed B Cell Lymphoma.
Official title: Interleukin-7 and Chemokine (C-C Motif) -Ligand 19-expressing CD19-CAR-T for Refractory/Relapsed B Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: B Cell Lymphoma
Keywords: interleukin 7, Chemokine (C-C Motif) Ligand 19, CAR-T
Lead sponsor: First Affiliated Hospital of Zhejiang University
Sponsor class: OTHER
Collaborators: name: Zhejiang Provincial Tongde Hospital
First posted: 2019-04-26
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: complete remission rate
timeFrame: at the time point 3 months after CAR-T cell transfusion
measure: adverse events
timeFrame: from the date of the start of treatment to 24 months after last patient's enrollment
Secondary outcomes:
measure: progression free surviva
timeFrame: from the day of treatment to the date of first documented progression，up to 24 months after the last patient's enrollment
measure: overall survival
timeFrame: from the day of treatment to the date of first documented progression，up to 24 months after the last patient's enrollment
measure: duration of the CAR-T cells in the patients
timeFrame: from the date of re-transfusison to 24 months after last patient's enrollment
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The first affiliated hospital of Zhejiang University
state: Zhejiang
Study officials:
affiliation: Zhejiang University
name: Wenbin Qian, MD，PhD
role: PRINCIPAL_INVESTIGATOR
References: