Memory-enriched CAR-T Cells Immunotherapy for B Cell Lymphoma
MeCAR
A Two-Arm, Single-Center, Open-Label Pilot Study of IL-2 Programmed or IL-7/IL-15 Programmed Anti-CD19:TCRz:CD28 T-cells in Patient With CD19-Positive Lymphoma That is Resistant or Refractory to Chemotherapy
1 other identifier
interventional
20
1 country
1
Brief Summary
The goal of this clinical trial is to study how approaches for manufacturing chimeric antigen receptor (CAR)-modified T (CAR-T) cells affect their in vivo persistence and therapeutic efficacy against B lymphoma. Recently, cancer immunotherapy, treatments aiming to arm patients with immunity specifically against cancer cells, has emerged as a promising therapeutic strategy. Among the many emerging immunotherapeutic approaches, clinical trials utilizing CARs against B cell malignancies have demonstrated remarkable potential. CARs combine the variable region of an antibody with T-cell signaling moieties to confer T-cell activation with the targeting specificity of an antibody. Thus, CARs are not MHC-restricted so they are not vulnerable to MHC down regulation by tumors. However, defined by the activation and contraction program of their mother cells, the persistency and function of CAR-T cells are also restricted by the protocol of manufacturing. Previous clinical studies largely utilized interleukin-2 (IL-2) for the ex vivo expansion of CAR-T cells, which preferentially generate CAR-T cells with characteristics of terminally differentiated effector cells. Our preliminary data indicated that two common gamma chain cytokines, IL-7 and IL-15, can help to selectively expand CAR-T cells with various memory phenotypes. CAR-T Cells prepared under this condition resulted in improved therapeutic efficacy in preclinical animal models. This clinical investigation is to test a hypothesis whether IL-7/IL-15-programmed anti-CD19 CAR-T cells persist longer in lymphoma patients after infusion and whether the persistency of CAR-T cells can lead to improved anti-lymphoma efficacy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Dec 2015
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 18, 2015
CompletedStudy Start
First participant enrolled
December 1, 2015
CompletedFirst Posted
Study publicly available on registry
January 12, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2019
CompletedFebruary 27, 2019
April 1, 2016
3.5 years
November 18, 2015
February 25, 2019
Conditions
Outcome Measures
Primary Outcomes (3)
Phase 1: Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0
4 weeks
Phase 2: Overall complete remission rate defined by the standard response criteria for malignant lymphoma for each arm
8 weeks
Phase 2: Comparison of overall complete remission rate for the two arms
One year
Secondary Outcomes (5)
Duration of remission
One year
Minimum residual disease negative remission rate
8 weeks
Duration of CAR-positive T cells in circulation
6 months
Total number of CAR-positive T cells infiltrated into lymphoma tissue
6 months
Overall survival
One year
Study Arms (2)
IL-2 programmed CD19.CAR-T cells
EXPERIMENTALAdministrated with IL-2 programmed CD19.CAR-T cells on day 0,1,2 in the lympho-depleted patients
IL-7/IL-15 programmed CD19.CAR-T cells
EXPERIMENTALAdministrated with IL-7/IL-15 programmed CD19.CAR-T cells on day 0,1,2 in the lympho-depleted patients
Interventions
Retroviral vector-transduced autologous T cells to express CD19-specific CARs
Eligibility Criteria
You may qualify if:
- Years to 70 Years, Male and female;
- Expected survival \> 12 weeks;
- Performance score 0-2;
- Histologically confirmed as CD19-positive lymphoma and who meet one of the following conditions;
- Patient receive at least 2-4 prior combination chemotherapy regimens (not including single agent monoclonal antibody therapy) and fail to achieve CR; or have disease recurrence; or not eligible for allogeneic stem cell transplantation; or disease responding or stable after most recent therapy but refused further treatment;
- Disease recurrence after stem cell transplantation;
- Diagnosis as lymphoma, but refuse conventional treatment such as chemotherapy, radiation, stem cell transplantation and monoclonal antibody therapy
- Creatinine \< 2.5 mg/dl;
- ALT/AST \< 3x normal;
- Bilirubin \< 2.0 mg/dl;
- Adequate venous access for apheresis, and no other contraindications for leukapheresis;
- Take contraceptive measures before recruit to this trial;
- Written voluntary informed consent is given.
You may not qualify if:
- Patients with symptoms of central nervous system
- Accompanied by other malignant tumor
- Active hepatitis B or C, HIV infection
- Any other diseases could affect the outcome of this trial
- Suffering severe cardiovascular or respiratory disease
- Poorly controlled hypertension
- A history of mental illness and poorly controlled
- Taking immunosuppressive agents within 1 week due to organ transplantation or other disease which need long-lasting administration
- Occurrence of unstable pulmonary embolism, deep vein thrombosis, or other major arterial/venous thromboembolic events 30 days prior to assignment
- Reaching a steady dose if receiving anticoagulant therapy before assignment
- Female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion
- Pregnant or lactating women
- Subject suffering disease affects the understanding of informed consent or comply with study protocol.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Xinqiao Hospital of Chongqinglead
- Xuzhou Medical Universitycollaborator
- Hrain Biotechnology Co., Ltd.collaborator
- Shanghai Changzheng Hospitalcollaborator
Study Sites (1)
Department of Oncology
Chongqing, Chongqing Municipality, 400000, China
Related Publications (1)
Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.
PMID: 34515338DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Bo Zhu, M.D., Ph.D.
Department of Cancer of Xinqiao Hospital
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Director of Department of Cancer
Study Record Dates
First Submitted
November 18, 2015
First Posted
January 12, 2016
Study Start
December 1, 2015
Primary Completion
June 1, 2019
Study Completion
December 1, 2019
Last Updated
February 27, 2019
Record last verified: 2016-04