Cell Therapy for CD7 Positive Acute Leukemia or Mixed Lineage Leukemia Except Those Who Are Diagnosed With T-ALL/T-LBL Using CD7-Specific CAR-T Cells
Study Details
Study Description
Brief Summary
This is an open, single-arm, clinical study to evaluate efficacy and safety of anti CD7 CAR-T cell in the treatment of CD7 Positive acute leukemia or mixed lineage leukemia except those who are diagnosed with T-ALL/T-LBL
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
The CARs consist of an anti-CD7 single-chain variable fragment（scFv）, a portion of the human CD137（4-1BB） molecule, and the intracellular component of the human CD3ζ molecule. Prior to CAR-T cell infusion, the patients will be subjected to preconditioning treatment. After CAR-T cell infusion, the patients will be evaluated for adverse reactions and efficacy.
The Main research objectives:
To evaluate the safety and efficacy of CD7 CAR-T cells in patients with CD7 Positive acute leukemia or mixed lineage leukemia except those who are diagnosed with T-ALL/T-LBL
The Secondary research objectives:
To investigate the cytokinetic characteristics of CD7 CAR-T cells in patients with CD7 Positive acute leukemia or mixed lineage leukemia except those who are diagnosed with T-ALL/T-LBL
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: CD7 CAR-T
|
Biological: CD7 CART
Biological: CD7 CAR-T; Drug: Cyclophosphamide,Fludarabine; Procedure: Leukapheresis
|
Outcome Measures
Primary Outcome Measures
- Safety: Incidence and severity of adverse events [First 1 month post CAR-T cells infusion]
To evaluate the possible adverse events occurred within first one month after CD7 CAR-T infusion, including the incidence and severity of symptoms such as cytokine release syndrome and neurotoxicity
- Efficacy: Remission Rate [3 months post CAR-T cells infusion]
In the presence of extramedullary lesions, complete remission (CR), partial remission (PR), stable disease (SD), disease recurrence or progression (PD) shall be used to describe extramedullary lesions
Secondary Outcome Measures
- duration of response (DOR) [24 months post CAR-T cells infusion]
duration of response (DOR)
- Efficacy: progression-free survival (PFS) [24 months post CAR-T cells infusion]
progression-free survival (PFS) time
- CAR-T proliferation [3 months post CAR-T cells infusion]
the copy number of CD7 CAR- T cells in the genomes of PBMC by qPCR method
- CAR-T proliferation [3 months post CAR-T cells infusion]
percentage of CD7 CAR- T cells measured by flow cytometry method
- Cytokine release [First 1 month post CAR-T cells infusion]
Cytokine( IL-6,IL-10,IFN-γ,TNF-α ) concentration (pg/mL) by flow cytometry method
- Pharmacokinetics (PK) indicators [24 months post CAR-T cells infusion]
the peak concentration of Senl-T7 CAR-T cells amplified in the peripheral blood (Cmax, detected by flow cytometry and qPCR); the time taken to reach the peak concentration (Tmax), and the persistent time of the Senl-T7 CAR-T cells in vivo in patients
- Pharmacodynamic (PD) indicators [First 1 month post CAR-T cells infusion]
the pharmacodynamic change in the clearance of peripheral blood CD7+ cells and the release of the cytokines at each observation time point
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Diagnosis of refractory or relapsed T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic lymphoma (T-LBL) according to the NCCN 2019.V2, the definition of refractory is failing to achieve complete remission after induction therapy ; the definition of relapse is either peripheral blood or bone marrow;
-
CD7-positive tumor (≥70% CD7 positive blasts by flow cytometry or immunohistochemistry (tissue) assessed by a CLIA certified Flow Cytometry/Pathology laboratory). tumors burden >5%,or MRD+， or new extramedullary lesions reappeared;
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Life expectancy greater than 12 weeks;
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KPS or Lansky score≥60;
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HGB≥70g/L (can be transfused);
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oxygen saturation of blood>90%;
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Total bilirubin (TBil)≤3 × upper limit normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5×upper limit of normal;
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Informed consent explained to, understood by and signed by patient/guardian
Exclusion Criteria:
-
Any of the following cardiac criteria: Atrial fibrillation/flutter; Myocardial infarction within the last 12 months; Prolonged QT syndrome or secondary prolonged QT, per investigator discretion. Cardiac echocardiography with LVSF (left ventricular shortening fraction)<30% or LVEF(left ventricular ejection fraction)<50%; or clinically significant pericardial effusion. Cardiac dysfunction NYHA(New York Heart Association) III or IV (Confirmation of absence of these conditions on echocardiogram within 12 months of treatment);
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Has an active GvHD;
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Has a history of severe pulmonary function damaging;
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With other tumors which is/are in advanced malignant and has/have systemic metastasis;
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Severe or persistent infection that cannot be effectively controlled；
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Merging severe autoimmune diseases or immunodeficiency disease;
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Patients with active hepatitis B or hepatitis C([HBVDNA+]or [HCVRNA+]);
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Patients with HIV infection or syphilis infection;
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Has a history of serious allergies on Biological products (including antibiotics);
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Clinically significant viral infection or uncontrolled viral reactivation of EBV(Epstein-Barr virus), CMV(cytomegalovirus), ADV(adenovirus), BK-virus, or HHV(human herpesvirus)-6;
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Presence of symptomatic disorders of the central nervous system, which include but not limited to uncontrolled epilepsy, cerebrovascular ischemia/hemorrhage, dementia, and cerebellar disease, etc.;
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Have received transplant treatment for less than 6 months in prior to enrollment;
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Being pregnant and lactating or having pregnancy within 12 months;
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Any situations that the researchers believe will increase the risks for the subject or affect the results of the study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | He bei Yan da Lu dao pei Hospital | Beijing | Hebei | China |
Sponsors and Collaborators
- Hebei Senlang Biotechnology Inc., Ltd.
Investigators
- Principal Investigator: Peihua MD Lu, PhD, Hebei Yanda Ludaopei Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CD7+ mixed lineage leukemia