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

B Cell Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03929107
• Other study ID #: lymphoma center Q003
• Status: Recruiting
• Phase: Phase 2
• Start date: March 28, 2019
• Est. completion date: April 30, 2022

Study information

• Verified date: April 2019
• Source: First Affiliated Hospital of Zhejiang University
• Contact: Juying Wei, MD
• Phone: (+86)13867476302
• Email: weijuy[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: April 30, 2022
• Est. primary completion date: January 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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: ?complete remission NOT achieved after 2nd line treatment; ?progression of disease during treatment; ?duration of stable disease <6 months; ? 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: ? failed or relapsed after 2nd therapy (Rituximab must be included) and being unable to accept ibrutinib treatment due to various reasons; ? non-responsive or intolerable to ibrutinib as 2nd line treatment; 3) refractory or relapsed MCL should fit one of the following: ? complete remission not achieved after 2nd line treatment; ? disease progression during treatment; ?duration of stable disease =6 months; ?disease 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.

Related Conditions & MeSH terms

• B Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell

Intervention

Biological:
• Interleukin-7 and Chemokine (C-C Motif) Ligand 19-expressing CD19-CAR-T cells
patient's T cells were seperated and engineered into Interleukin-7 and Chemokine (C-C Motif) Ligand 19-expressing CD19-CAR-T cells, and retransfused into the patient for treatment of their B cell lymphoma.

Locations

Country	Name	City	State
China	The first affiliated hospital of Zhejiang University	Hangzhou	Zhejiang

Sponsors (2)

Lead Sponsor	Collaborator
Wenbin Qian	Zhejiang Provincial Tongde Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	complete remission rate	complete remission rate after treated by CAR-T therapy	at the time point 3 months after CAR-T cell transfusion
Primary	adverse events	any unfavorable and unintended sign , symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure	from the date of the start of treatment to 24 months after last patient's enrollment
Secondary	progression free surviva	from date of inclusion to date of progression, relapse, or death from any cause	from the day of treatment to the date of first documented progression,up to 24 months after the last patient's enrollment
Secondary	overall survival	from the date of inclusion to date of death, irrespective of cause	from the day of treatment to the date of first documented progression,up to 24 months after the last patient's enrollment
Secondary	duration of the CAR-T cells in the patients	time from re-transfusion to date when the modified T cells become non-detectable.	from the date of re-transfusison to 24 months after last patient's enrollment