Clinical trial NCT06420076: Sequential CAR-T Cells Therapy for CD5/CD7 Positive T-cell Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma Using CD5/CD7-Specific CAR-T Cells
Official title: This is an Open, Single-arm, Clinical Study to Evaluate the Efficacy and Safety of Anti-CD7/CD5 CAR-T Cells in the Treatment of Relapsed or Refractory T-cell Acute Lymphoblastic Leukemia (T-ALL), ETP-ALL, and Lymphoblastic Lymphoma (TLBL).
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: T Cell Lymphoma
T Cell Leukemia
T-cell Acute Lymphoblastic Leukemia
T-Cell Lymphoma of CNS
T Cell Prolymphocytic Leukemia
T Cell Childhood ALL
Keywords: CAR-T
CD5
CD7
ETP-ALL
Lead sponsor: Essen Biotech
Sponsor class: OTHER
First posted: 2024-05-17
Enrollment: 60
Sex: ALL
Minimum age (years): 2
Maximum age (years): 90
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Patients enrolled in this clinical trial will receive a carefully designed treatment regimen. Prior to the infusion of CD5 and CD7 CAR-T cells, participants will undergo preconditioning chemotherapy. This chemotherapy serves to create an optimal environment for CAR-T cell therapy to effectively target and eliminate malignant B cells. Following chemotherapy, participants will receive the infusion of CD5 and CD7 CAR-T cells.
Primary purpose: TREATMENT

Brief summary: Chimeric antigen receptor (CAR)-modified T cells targeted against CD19 have demonstrated unprecedented successes in treating patients with hematopoietic and lymphoid malignancies. Besides CD19, many other molecules such as CD22, CD30,BCMA,CD123, etc. may be the potential to develop the corresponding CAR-T cells to treat patients whose tumors express those markers. In this study, investigators will evaluate the safety and efficacy of Sequential CAR-T Cells Targeting CD5/CD7 in patients with patients with relapsed or refractory T-ALL/LBL/ETP-ALL. The primary goal is safety assessment including cytokine storm response and any other adverse effects. In addition, disease status after treatment will also be evaluated.

Detailed description: Acute lymphoblast leukemia (T-ALL) is a neoplastic lymphoid leukemia characterized by the proliferation of immature precursor T cells. The combined chemotherapy has significantly improved the prognosis of T-acute lymphoblast leukemia/lymphoma. However, once the disease appears to be relapsed/refractory, there are limited treatment options, and the overall prognosis is extremely poor. Therefore, exploring safe and effective treatments is a critical unmet medical need. The patients will receive Sequential CAR-T Cells Targeting CD5/CD7 to examine the safety and, possibly the efficacy of CD5 CAR T-Cells in CD5+ CD7+ relapsed or refractory acute leukemia.

Eligibility criteria: Inclusion Criteria:

* Signed written informed consent; Patients volunteer to participate in the clinical trial;
* Diagnosis is mainly based on the World Health Organization (WHO) 2008;
* Complete remission cannot be achieved after induction therapy; recurrence occurs after completion remission; the burden of leukemic blasts in the peripheral blood or bone marrow is greater than 5%;
* Leukemic blast cells express CD7/CD5 (CD7 OR CD5 positive by flow cytometry or immunohistochemistry ≥70%);
* The expected survival period is greater than 12 weeks;
* ECOG score ≤2;
* Age 2-60 years old;
* HGB≥70g/L (can be transfused);
* Total bilirubin does not exceed 3 times the upper limit of normal value, and AST and ALT do not exceed 5 times the upper limit of normal value.

Exclusion Criteria:

* Patients declining to consent for treatment
* Prior solid organ transplantation
* One of the following cardiac issues: atrial fibrillation; myocardial infarction within the past 12 months; prolonged QT syndrome or secondary QT prolongation; clinically significant pericardial effusion; cardiac insufficiency NYHA (New York Heart Association) III or IV;
* History of severe pulmonary dysfunction diseases;
* Severe infection or persistent infection cannot be effectively controlled;
* Severe autoimmune disease or congenital immunodeficiency;
* Active hepatitis;
* Human immunodeficiency virus (HIV) infection;
* Clinically significant viral infections, or uncontrollable viral reactivation, including EBV (Epstein-Barr virus).

Primary outcomes:
measure: The number and incidence of adverse events after CD7/CD5 CAR infusion.
timeFrame: 28 days
measure: Disease response to CD7/CD5 CAR T cells
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Beijing
country: China
facility: District One Hospital
state: Beijing
Study officials:
References: