Decitabine-primed Tandem CD19/CD20 CAR T Cells Plus Epigenetic Agents in Aggressive r/r B-NHL With Huge Tumor Burden
NCT ID: NCT04553393
Last Updated: 2020-12-04
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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UNKNOWN
PHASE1/PHASE2
80 participants
INTERVENTIONAL
2020-09-09
2022-09-08
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Decitabine-primed Tandem CAR19/20 engineered T cells
Tandem dual Specificity targeting CD19 and CD20 decitabine-primed CAR-T cells can recognize and kill the CD19 negative malignant cells through recognition of CD20 and improve the possibility of killing lymphoma tumor cells.
Decitabine-primed Tandem CAR19/20 engineered T cells
Tandem CAR19/20 engineered T cells
Decitabine-primed Tandem CAR19/20 engineered T cells plus chidamide
Chidamide is a novel and orally active benzamide class of HDAC inhibitor that selectively inhibits activity of HDAC1, 2, 3 and 10, which can Induce tumor-cell apoptosis, suppress cell proliferation and enhance immune surveillance.
Chidamide
Chidamide will be added 1 month after responding to CART cells infusion
Decitabine-primed Tandem CAR19/20 engineered T cells
Tandem CAR19/20 engineered T cells
Decitabine-primed Tandem CAR19/20 engineered T cells plus decitabine
Decitabine is an investigational (experimental) drug that works by depleting DNA methyltransferase 1(DNMT1), which can increase tumor antigens and HLA expression, enhances antigen processing, promotes T cell infiltration, and boosts effector T cell function.
Decitabine
Decitabine will be added 1 month after responding to CART cells infusion
Decitabine-primed Tandem CAR19/20 engineered T cells
Tandem CAR19/20 engineered T cells
Decitabine-primed Tandem CAR19/20 engineered T cells plus chidamide+decitabine
The combination of chidamide and decitabine can increase tumor antigens and HLA expression, enhances antigen processing, promotes T cell infiltration, and boosts effector T cell function, induce tumor-cell apoptosis, suppress cell proliferation and enhance immune surveillance
Chidamide and Decitabine
Both chidamide and decitabine will be added 1 month after responding to CART cells infusion
Decitabine-primed Tandem CAR19/20 engineered T cells
Tandem CAR19/20 engineered T cells
Interventions
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Chidamide
Chidamide will be added 1 month after responding to CART cells infusion
Decitabine
Decitabine will be added 1 month after responding to CART cells infusion
Chidamide and Decitabine
Both chidamide and decitabine will be added 1 month after responding to CART cells infusion
Decitabine-primed Tandem CAR19/20 engineered T cells
Tandem CAR19/20 engineered T cells
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Sum of the Product of the perpendicular Diameters for multiple lesions, SPD ≥ 100cm\^2 or the largest-diameter of tumor ≥ 10cm.
3. Histologically confirmed CD20+ and/or CD19+ aggressive B-cell non-Hodgkin lymphoma (NHL), including the following types defined by the World Health Organization (WHO) 2016:
* Diffuse large B-cell lymphoma (DLBCL).
* High grade B-cell lymphoma(HGBL).
* Other aggressive B-cell lymphoma.
4. Refractory disease or relapse after treatment with ≥2 lines of chemotherapy, including rituximab and anthracycline and either having failed autologous hematopoietic stem cell transplantation (HSCT), being ineligible for autologous HSCT or not consenting to autologous HSCT.
We defined chemotherapy-refractory disease as meeting one or more of the following criteria:
* No response to first-line therapy (primary refractory disease).
* No response to second-line or later therapy.
* Progressive disease (PD) as the best response to the most recent therapy regimen.
* Stable disease (SD) as the best response after at least 2 cycles of the most recent line of therapy with an SD duration of no longer than 6 months from the last dose of therapy.
Failure following autologous HSCT was defined as follows:
* PD or relapsed disease ≤12 months after autologous stem cell transplantation (ASCT) (requires biopsy-proven recurrence in relapsed subjects).
* No response or relapse after salvage therapy is given post-ASCT.
5. PD or relapse ≥3 months after treatment with targeted CD19 therapy, including CD19 CAR T cells or anti-CD19/anti-CD3.
6. Successful leukapheresis assessment and preculture of T cells.
7. Life expectancy \> 3 months.
8. Adequate organ function:
* Creatinine \< 1.6 mg/dL (140 µmol/L) or creatinine clearance ≥60 mL/min.
* Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) \< 3× upper limit of the normal range.
* Bilirubin \<2.0 mg/dL unless the subject had Gilbert's syndrome (\<3.0 mg/dL).
* A minimum level of pulmonary reserve defined as ≤ grade 1 dyspnoea and pulse oxygenation \> 91% with room air.
* Cardiac ejection fraction ≥50%, no evidence of pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings.
9. An adequate bone marrow reserve defined as:
* Absolute neutrophil count (ANC)\>1,000/mm3.
* Absolute lymphocyte count (ALC)≥300/mm3.
* Platelet count ≥ 50,000/mm3.
* Haemoglobin \> 7.0 mg/dL.
10. Measurable or assessable disease according to the "IWG Response Criteria for Malignant Lymphoma" (Cheson 2014). Patients in complete remission (CR) with no evidence of disease were not eligible.
11. Informed consent/assent requiring that all patients have the ability to understand and the willingness to provide written informed consent.
Exclusion Criteria
2. Detection of a clear HAMA effect in patients with prior CD19 CAR T cell treatment failure or recurrence, or negative tumour puncture detection of CD19 and CD20.
3. Pregnant or lactating women.
4. Uncontrolled active bacterial or viral infection (active hepatitis B or hepatitis C infection, HIV infection) or treponema pallidum infection.
5. Class III/IV cardiovascular disability according to the New York Heart Association Classification and a cardiac ejection fraction ≥50%.
6. History of allo-HSCT.
7. Requirement for urgent therapy due to tumour mass effects such as respiratory obstruction or blood vessel compression.
8. Current or expected need for systemic corticosteroid therapy.
9. Any organ failure.
10. Patients with a second tumour requiring therapy or intervention.
11. Eastern Cooperative Oncology Group (ECOG) performance status score between 0 and 2.
12. Subjects considered unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation according to the investigator's judgement.
16 Years
65 Years
ALL
No
Sponsors
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Chinese PLA General Hospital
OTHER
Responsible Party
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Han weidong
Professor
Principal Investigators
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Weidong Han, M.D.
Role: PRINCIPAL_INVESTIGATOR
Chinese PLA Hospital
Locations
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Biotherapeutic Department of Chinese PLA General Hospital
Beijing, Beijing Municipality, China
Countries
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Central Contacts
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Facility Contacts
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Weidong Han, M.D
Role: primary
Other Identifiers
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CHN-PLAGH-BT-060
Identifier Type: -
Identifier Source: org_study_id