Description:
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).
Title
- Brief Title: Cell Therapy for CD7 Positive T-cell Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma Using CD7-Specific CAR-T Cells
- Official Title: Cell Therapy for CD7 Positive T-cell Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma Using CD7-Specific CAR-T Cells
Clinical Trial IDs
- ORG STUDY ID:
CD7 CAR-T for T-ALL/T-LBL
- NCT ID:
NCT04572308
Conditions
- T-cell Acute Lymphoblastic Leukemia/Lymphoma
Interventions
Drug | Synonyms | Arms |
---|
CD7 CAR-T | | CD7 CAR-T |
Purpose
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
Trial Arms
Name | Type | Description | Interventions |
---|
CD7 CAR-T | Experimental | Patients will be treated with CD7 CAR-T cells | |
Eligibility Criteria
Inclusion Criteria:
1. 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.
2. 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.
3. Life expectancy greater than 12 weeks
4. KPS or Lansky score≥60
5. HGB≥70g/L
6. oxygen saturation of blood>90%
7. Total bilirubin (TBil)≤3 × upper limit normal, aspartate aminotransferase (AST) and
alanine aminotransferase (ALT) ≤ 5×upper limit of normal
8. Informed consent explained to, understood by and signed by patient/guardian.
Exclusion Criteria:
1. 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)
2. Has an active GvHD;
3. Has a history of severe pulmonary function damaging;
4. With other tumors which is/are in advanced malignant and has/have systemic metastasis;
5. Severe or persistent infection that cannot be effectively controlled;
6. Presence of severe autoimmune diseases or immunodeficiency disease;
7. Patients with active hepatitis B or hepatitis C([HBVDNA+]or [HCVRNA+]);
8. Patients with HIV infection or syphilis infection;
9. Has a history of serious allergies to biological products (including antibiotics);
10. Clinically significant viral infection or uncontrolled viral reactivation of
EBV(Epstein-Barr virus), CMV(cytomegalovirus), ADV(adenovirus), BK-virus, or HHV(human
herpesvirus)-6.
11. 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;
12. Received allogeneic hematopoietic stem cell transplantation within 6 months;
13. Being pregnant and lactating or having pregnancy within 12 months;
14. Any situations that the researchers believe will increase the risks for the subject or
affect the results of the study.
Maximum Eligible Age: | 65 Years |
Minimum Eligible Age: | 2 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Safety: Incidence and severity of adverse events |
Time Frame: | First 1 month post CAR-T cells infusion |
Safety Issue: | |
Description: | 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 |
Secondary Outcome Measures
Measure: | duration of response (DOR) |
Time Frame: | 24 months post CAR-T cells infusion |
Safety Issue: | |
Description: | duration of response (DOR) |
Measure: | Efficacy: progression-free survival (PFS) |
Time Frame: | 24 months post CAR-T cells infusion |
Safety Issue: | |
Description: | progression-free survival (PFS) time |
Measure: | CAR-T proliferation |
Time Frame: | 3 months post CAR-T cells infusion |
Safety Issue: | |
Description: | the copy number of CD7 CAR- T cells in the genomes of PBMC by qPCR method |
Measure: | CAR-T proliferation |
Time Frame: | 3 months post CAR-T cells infusion |
Safety Issue: | |
Description: | percentage of CD7 CAR- T cells measured by flow cytometry method |
Measure: | Cytokine release |
Time Frame: | First 1 month post CAR-T cells infusion |
Safety Issue: | |
Description: | Cytokine( IL-6,IL-10,IFN-γ,TNF-α ) concentration (pg/mL) by flow cytometry method |
Measure: | Pharmacokinetics (PK) indicators: |
Time Frame: | Long time |
Safety Issue: | |
Description: | 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; |
Measure: | Pharmacodynamic (PD) indicators: |
Time Frame: | First 1 month post CAR-T cells infusion |
Safety Issue: | |
Description: | the pharmacodynamic change in the clearance of peripheral blood CD7+ cells and the release of the cytokines at each observation time point |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | Hebei Senlang Biotechnology Inc., Ltd. |
Trial Keywords
Last Updated
June 29, 2021