thiscart19a bridging to allohsct for r/r b-all

Conditions: CAR; Refractory Acute Lymphoblastic Leukemia; Relapsed Adult ALL

Summary: this is a phase 1, open-label study to assess the efficacy, safety and pharmacokinetics of thiscart19a (allogeneic anti cd19 car-t) bridging to hsct in patients with refractory or relapsed b cell acute lymphoblastic leukemia (r/r b-all).

this is a phase 1, single-center, nonrandomized, open-label, dose-escalation study to evaluate the efficacy, safety and pharmacokinetics of thiscart19a bridging to hsct in patients with cd19 positive r/r b-all and identify a treatment regimen most likely to result in clinical efficacy while maintaining a favorable safety profile. before initiating thiscart19a infusion, subjects will be administered lymphodepletion chemotherapy composed of fludarabine、cyclophosphamide and vp-16. at day 0 of the treatment period, subjects will receive an intravenous (iv) infusion of thiscart19a. all subjects are monitored during the treatment period through day 28. all subjects who receive a dose of thiscart19a will be followed up to 2 years.

Eligibility criteria:
inclusion criteria: 1. voluntarily sign a documented irb-approved icf prior to any screening procedure. 2. no gender limitation, 14 years ≤ age ≤ 65 years. 3. intention to hsct therapy. 4. meeting the diagnostic criteria of relapsed or refractory b-all. relapsed b-all: reappearance of blasts in the blood or bone marrow (\>5%) or in any extramedullary site after a cr. refractory b-all: failure to achieve cr or cri at the end of induction therapy (general refers to a 4-week regimen or a hyper-cvad regimen); subjects with ph+ disease are eligible if they are intolerant to tki therapy, or if they have relapsed/refractory disease despite treatment with at least 2 different tkis. 5. life expectancy ≥ 8 weeks at the time of enrollment. 6. eastern cooperative oncology group performance status score of 0 or 1. 7. adequate bone marrow, renal, hepatic, pulmonary and cardiac function: 1. adequate marrow function for lymphodepletion chemotherapy assessed by the investigator. 2. creatinine clearance \> 30 ml/min according to the cockcroft-gault formula; 3. alt and ast ≤ 5 × uln (the upper limit of normal), total bilirubin ≤ 2×uln. (subjects with gilbert syndrome or liver involvement may be included if their total bilirubin is ≤ 3 × uln.) 4. oxygen saturation (sao2) ≥ 92% on room air. 5. cardiac function：left ventricular ejection fraction (lvef) ≥ 40% assessed by echocardiography. 8. cd19-positive leukemia obtained from bone marrow or peripheral blood confirmed by flowcytometry or biopsy during screening. exclusion criteria: 1. allergic to preconditioning measures. 2. history of allogeneic hsct. 3. other malignancies apart from b-cell malignancies within 5 years prior to screening. (subjects with cured skin squamous carcinoma, basal cell carcinoma, non-primary invasive bladder cancer, localized low-risk prostate cancer, in situ cervical/breast cancer can be enrolled.) 4. severe active infection. (simple urinary tract infection (uti) and uncomplicated bacterial pharyngitis are permitted.) 5. pulmonary embolism within 3 months prior to enrollment. 6. severe cardiovascular and cerebrovascular diseases and hereditary diseases intolerant to car-t therapy assessed by the investigator prior to enrollment. 7. presence of symptomatic cns involvement (both primary and secondary) at screening confirmed by imaging; 8. active hepatitis b virus (defined as serum hbv-dna ≥ 2000 iu/ml), hepatitis c virus (hcv), human immunodeficiency virus (hiv) or active syphilis infection prior to enrollment. (subjects with hbv-dna \< 2000 iu/ml can be enrolled, but should be administered antiviral drugs such as entecavir and tenofovir with relative clinical indicators monitored simultaneously during the treatment.) 9. vaccinated with influenza vaccine within 2 weeks prior to lymphodepletion chemotherapy. (subjects vaccinated with sars-cov19 vaccine or inactivated, live/non-live adjuvant vaccines can be enrolled.) 10. female subjects who are pregnant, breastfeeding or planning for pregnancy within 1 year after car-t cell infusion, or male subjects whose partners are planning for pregnancy within 1 year after car-t cell infusion. 11. any conditions that would, in the investigator's assessment, increase risks in patients or interfere with the outcomes of the trial.

Keywords: universal car-t allogeneic hct