cd5 car-t therapy for refractory/relapsed cd5+ t-cell acute lymphoblastic leukemia

Conditions: T-cell Acute Lymphoblastic Leukemia

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.

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.

Keywords: cd5 car-t t-all