Cell Therapy for CD7 Positive T-cell Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma Using CD7-Specific CAR-T Cells
- Conditions
- T-cell Acute Lymphoblastic Leukemia/Lymphoma
- Interventions
- Biological: CD7 CAR-T
- Registration Number
- NCT04572308
- Lead Sponsor
- Hebei Senlang Biotechnology Inc., Ltd.
- 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 relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) and lymphoblastic lymphoma (TLBL).
- 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 relapsed or refractory T-ALL/LBL
The Secondary research objectives:
To investigate the cytokinetic characteristics of CD7 CAR-T cells in patients with relapsed or refractory T-ALL/LBL
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 20
- Diagnosis of refractory or relapsed T-cell acute lymphoblastic leukemia (T-ALL) or lymphoblastic lymphoma (T-LBL) according to the NCCN 2019.V2 Guideline. Refractory T-ALL is defined as a patient who has failed to achieve complete remission after induction therapy. Relapsed T-ALL is defined as the reappearance of blasts (5%) in either peripheral blood or bone marrow. Patients whose tumor burden >5% blasts, or who have persistent positive minimal residual disease (MRD), or have reappearance of extramedullary lesions are also considered eligible.
- 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.
- Life expectancy greater than 12 weeks
- KPS or Lansky score≥60
- HGB≥70g/L
- oxygen saturation of blood>90%
- Total bilirubin (TBil)≤3 × upper limit normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5×upper limit of normal
- Informed consent explained to, understood by and signed by patient/guardian.
- 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)
- Has an active GvHD;
- Has a history of severe pulmonary function damaging;
- With other tumors which is/are in advanced malignant and has/have systemic metastasis;
- Severe or persistent infection that cannot be effectively controlled；
- Presence of severe autoimmune diseases or immunodeficiency disease;
- Patients with active hepatitis B or hepatitis C([HBVDNA+]or [HCVRNA+]);
- Patients with HIV infection or syphilis infection;
- Has a history of serious allergies to biological products (including antibiotics);
- Clinically significant viral infection or uncontrolled viral reactivation of EBV(Epstein-Barr virus), CMV(cytomegalovirus), ADV(adenovirus), BK-virus, or HHV(human herpesvirus)-6.
- Presence of any symtomatic CNS disorder such as an uncontrolled seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement;
- Received allogeneic hematopoietic stem cell transplantation within 6 months;
- Being pregnant and lactating or having pregnancy within 12 months;
- Any situations that the researchers believe will increase the risks for the subject or affect the results of the study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description CD7 CAR-T CD7 CAR-T Patients will be treated with CD7 CAR-T cells
- Primary Outcome Measures
Name Time Method Safety: Incidence and severity of adverse events First 1 month post CAR-T cells infusion To evaluate the possible adverse events occurred within the 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 Remission Rate including complete remission(CR)、CR with incomplete blood count recovery(CRi)、partial remission(PR), No remission(NR), overall remission (OR)
- Secondary Outcome Measures
Name Time Method 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 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: Long time 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
Trial Locations
- Locations (1)
Hebei yanda Ludaopei Hospital
🇨🇳Yanda, Hebei, China