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

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

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.

Study Overview

• Status: Unknown
• Conditions: B Cell Lymphoma
• Intervention / Treatment: Biological: Interleukin-7 and Chemokine (C-C Motif) Ligand 19-expressing CD19-CAR-T cells

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • The First Affiliated Hospital of Zhejiang University
      • Contact: Wenbin Qian, MD,PhD; Phone Number: (+86)13605801032; Email: qianwenb@aliyun.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention group; 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.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
complete remission rate	complete remission rate after treated by CAR-T therapy	at the time point 3 months after CAR-T cell transfusion
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Collaborators and Investigators

• Sponsor: Wenbin Qian
• Collaborators: Zhejiang Provincial Tongde Hospital
• Investigators: Principal Investigator: Wenbin Qian, MD，PhD, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2019
• Primary Completion (Anticipated): January 31, 2022
• Study Completion (Anticipated): April 30, 2022

Study Registration Dates

• First Submitted: April 22, 2019
• First Submitted That Met QC Criteria: April 25, 2019
• First Posted (Actual): April 26, 2019

Study Record Updates

• Last Update Posted (Actual): April 26, 2019
• Last Update Submitted That Met QC Criteria: April 25, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: interleukin 7, Chemokine (C-C Motif) Ligand 19, CAR-T
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell
• Other Study ID Numbers: lymphoma center Q003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No