Safety and Efficacy of Metabolically Armed CD19 CAR-T Cells (Meta10-19) in the Treatment of r/r DLBCL Clinical Research
Study Details
Study Description
Brief Summary
A Study of Metabolically Armed CD19 CAR-T Cells Therapy for Patients With Relapsed and/or Refractory Diffuse Large B-Cell Lymphoma
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Early Phase 1 |
Detailed Description
This is a single arm, open-label study. This study is indicated for relapsed or refractory CD19+ Diffuse Large B-Cell Lymphoma. The selections of dose levels and the number of subjects are based on clinical trials of similar foreign products.
- Main research objectives:
To evaluate the safety and efficacy of metabolically armed CD19 CAR-T Cells in the treatment of r/r DLBCL.
- Secondary research objectives:
（1）To evaluate the pharmacokinetic (PK) and pharmacodynamics(PD) characteristics of metabolically armed CD19 CAR-T Cells after infusion.
（2）To evaluate tumor remission after infusion of metabolically armed CD19 CAR-T Cells.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Administration of Metabolically Armed CD19 CAR-T cells Patients undergo leukapheresis. Patients will receive a lymphodepletion chemotherapy with cyclophosphamide and fludarabine before CAR-T cells infusion. A dose of metabolically armed CD19 CAR-T cells will be infused on day 0. |
Drug: Metabolically Armed CD19 CAR-T cells
Each subject receive metabolically armed CD19 CAR-T cells by intravenous infusion
Other Names:
|
Outcome Measures
Primary Outcome Measures
- MTD [MTD will be determined based on DLTs observed during the first 28 days of study treatment.]
Determine the Maximal Tolerable Dose(MTD)
- Objective response rate (ORR) [Within 3 months following infusion of Meta10-19]
Measure Tumor response rate (including CR and PR) .
Secondary Outcome Measures
- Pharmacokinetics [Up to 12 months after CAR-T treatment]
The number of CAR-T cells in peripheral blood was measured to evaluate the persistence of CAR-T cells
- Pharmacodynamics [Up to 28 days after infusion]
Peak level of cytokines in peripheral blood
Eligibility Criteria
Criteria
Inclusion Criteria:
-
The patient or his/her guardian voluntarily signed the informed consent;
-
Adult Patients with relapsed and refractory diffuse large B-cell lymphoma (Primary mediastinal large B-cell lymphoma and transformed follicular lymphoma are included)
Definition of refractory:
- No response to the last treatment, including:
The best response to the last treatment was PD, or ; The best response to the last treatment was SD and the duration was not more than 6 months after the last dose.
- Not suitable for autologous hematopoietic stem cell transplantation (ASCT), or
ASCT refractory, including:
Disease progression or recurrence within 12 months or less (recurrence must be confirmed by biopsy) after ASCT treatment, or; Patients accept remedial treatment after ASCT must have no response or relapse after the last treatment.
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Patients who had previously received ≥2 lines therapy including at least:
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A chemotherapy regimen containing anthracyclines；
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For patients with transformed DLBCL from follicular lymphoma, they must have previously received chemotherapy for follicular lymphoma and have refractory disease after transformation to DLBCL.
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CD19 expression was positive by immunohistochemistry or flow cytometry (accept the results of this peripheral blood mononuclear cells or previous report from a Class A tertiary hospital before peripheral blood collection)
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At least one measurable lesion at baseline, according to the initial assessment, staging and Response Assessment recommendations for Hodgkin's and non-Hodgkin's lymphoma (2014 edition)
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Expected survival time greater than 12 weeks
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The baseline ECOG score was 0 or 1
-
organ function：
-
Kidney function is defined as:
Serum creatinine ≤1.5 times ULN, or； The glomerular filtration rate (eGFR) estimated by MDRD formula was ≥60m/min/1.73m2；[eGFR=186×（age）-0.203×SCr-1.154（mg/dl），for females, the result was ×0.742]；
-
Liver function is defined as： ALT≤5 times ULN, and; Patients with total bilirubin ≤2.0mg/dl, except those with Gilbert-Meulengracht syndrome. Patients with Gilbert-.Meulengracht syndrome with total bilirubin ≤3.0 times ULN and direct bilirubin ≤1.5 times ULN were included.
-
Pulmonary function: ≤CTCAE grade 1 dyspnea and oxygen saturation of blood (SaO2) ≥91% in indoor air environment.
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Hemodynamic stability was determined by echocardiography or multichannel radionuclide angiography (MUGA) and LVEF ≥45％
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Patients using the following drugs must meet the following conditions:
-
Steroid: Therapeutic doses of steroids must be discontinued 2 weeks prior to Meta10-19 infusion. However, physiological replacement doses of steroids are permitted, hydrocortisone or its equivalent < 6-12mg/mm2/ day；
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Immunosuppressive agent: Any immunosuppressive drug must be stopped ≥4 weeks before the informed consent is signed
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Anti-proliferative therapy in addition to preconditioning chemotherapy 2 weeks prior to Meta10-19 infusion
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Treatment for CNS disease must be stopped 1 week before Meta10-19 infusion (e.g., intrathecal methotrexate)
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The patient has recovered from the toxicity of the previous treatment, that is, the CTCAE toxicity grade is less than 1 (The exception is specific toxicity of grade 2 or less, such as hair loss, which the researchers have determined is not recoverable in a short period of time) is suitable for pretreatment chemotherapy and CAR T cell therapy
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Women of childbearing age and all male patients must consent to use a effective contraception for at least 12 months after Meta10-19 infusion and until two consecutive PCR tests show no more CAR T cells in vivo；
Exclusion Criteria:
-
Patients with detectable cerebrospinal fluid malignant cells or brain metastases, or a history of central nervous system (CNS) lymphoma or primary CNS lymphoma
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Patients with present or history of central nervous system diseases such as seizures disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement
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Patients with history of allogeneic hematopoietic stem cell transplantation
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Patients who had received chemotherapy other than preconditioning chemotherapy within 2 weeks prior to Meta10-19 infusion
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Patients who participated in other clinical trials within 30 days prior to enrollment
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Patients with active hepatitis B (defined as hepatitis B surface antigen positive or hepatitis B core antibody positive, concomitant hepatitis B virus DNA level > 1000 copies/ml) or hepatitis C (HCV RNA positive)
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Patients with HIV antibody positive or treponema pallidum antibody positive
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Patients with uncontrolled acute life-threatening bacterial, viral or fungal infections (e.g. positive blood cultures ≤72 hours before Meta10-19 infusion)
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Patients with unstable angina pectoris and/or myocardial infarction within 6 months prior to enrollment
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Patients with history of other malignancies, but the following conditions can be enrollment:
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Adequately treated basal or squamous cell carcinoma (requiring adequate wound healing before signing informed consent);
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Carcinoma in situ (DCIS) of cervical or breast cancer, which has been treated therapeutically, has shown no signs of recurrence for at least 3 years prior to the signing of the informed consent；
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The primary malignancy has been completely resected and in complete remission for ≥5 years；
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Women who are pregnant or breastfeeding (pregnancy tests for women of childbearing age are positive)
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Patients with active neuroautoimmune or inflammatory conditions (e.g. Guillian-Barre syndrome, amyotrophic lateral sclerosis);
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Other conditions that the investigator considered should not be enrolled in this clinical study, such as poor compliance.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Anhui Provincial Hospital | Hefei | Anhui | China |
Sponsors and Collaborators
- Anhui Provincial Hospital
- Leman Biotech Co., Ltd
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2022KY319