Cell Therapy for CD7 Positive T-cell Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma Using CD7-Specific CAR-T Cells
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- T-cell Acute Lymphoblastic Leukemia/Lymphoma
- Sponsor
- Hebei Senlang Biotechnology Inc., Ltd.
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Safety: Incidence and severity of adverse events
- Status
- Completed
- Last Updated
- 4 years ago
Overview
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
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
- •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.
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)
- •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)-
Outcomes
Primary Outcomes
Safety: Incidence and severity of adverse events
Time Frame: 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
Time Frame: 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 Outcomes
- duration of response (DOR)(24 months post CAR-T cells infusion)
- Efficacy: progression-free survival (PFS)(24 months post CAR-T cells infusion)
- CAR-T proliferation(3 months post CAR-T cells infusion)
- Cytokine release(First 1 month post CAR-T cells infusion)
- Pharmacokinetics (PK) indicators:(Long time)
- Pharmacodynamic (PD) indicators:(First 1 month post CAR-T cells infusion)