Clinical trial NCT05596266: CD5 CAR-T Therapy for Refractory/Relapsed CD5+ T-cell Acute Lymphoblastic Leukemia
Official title: A Phase I Study of CD5 CAR-T for Refractory/Relapsed CD5+ T-ALL Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: T-cell Acute Lymphoblastic Leukemia
Keywords: CD5 CAR-T
T-ALL
Lead sponsor: Xuanwu Hospital, Beijing
Sponsor class: OTHER
Collaborators: name: Baoding Children's Hospital
First posted: 2022-10-27
Enrollment: 20
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a phase I, interventional, single arm, open label, clinical study to evaluate the safety and tolerability of CD5 CAR-T cells in refractory/relapsed CD5+ T-ALL patients who have no available curative treatment options.

Detailed description: T-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 is 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 infusion of CAR T-cells targeting CD5 to examine the safety and, possibly the efficacy of CD5 CAR T-Cells in CD5+ relapsed or refractory acute leukemia.

Eligibility criteria: Inclusion Criteria:

1. Diagnosis of refractory or relapsed T-cell acute lymphoblastic leukemia (T-ALL) 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. CD5-positive tumor (≥70% CD5 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. Aged 1 to 18 years (including 18 years old);
4. Eastern Cooperative Oncology Group (ECOG) score 0-2;
5. Life expectancy greater than 12 weeks;
6. Oxygen saturation of blood\>90%;
7. Total bilirubin (TBil) ≤3 × upper limit normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 10 × upper limit of normal;
8. Informed consent explained to, understood by and signed by patient/guardian.

Exclusion Criteria:

1. Intracranial hypertension or brain consciousness disorder;
2. Has an active GvHD;
3. Has a history of severe pulmonary function damaging;
4. With other tumors which is/are in advanced malignant stage 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 symptomatic 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 risk for the subject or affect the results of the study.

Primary outcomes:
measure: Safety: Incidence and severity of adverse events
timeFrame: First 1 month post CAR-T cells infusion
Secondary outcomes:
measure: Efficacy: Remission Rate
timeFrame: 1 months post CAR-T cells infusion
measure: Best overall response (BOR)
timeFrame: 1 months
measure: Duration of remission (DoR)
timeFrame: 1 year
measure: Event free survival within 1 year
timeFrame: 1 year
Other outcomes:
Locations:
city: Beijing
country: China
facility: Xuanwu Hospital Capital Medical University
state: Beijing
Study officials:
affiliation: Xuanwu Hospital, Beijing
name: Zhiguo Chen, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Baoding Children's Hospital; Beijing Children's Hospital, Capital Medical University
name: Huyong Zheng, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: