A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Allogeneic Anti CD19 CAR-T Bridging to Hematopoietic Stem Cell Transplantation in Patients With Refractory or Relapsed B Cell Acute Lymphoblastic Leukemia
Overview
- Phase
- Phase 1
- Intervention
- Treatment
- Conditions
- CAR
- Sponsor
- The First Affiliated Hospital of Soochow University
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- ORR
- Status
- Recruiting
- Last Updated
- 3 years ago
Overview
Brief 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).
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Voluntarily sign a documented IRB-approved ICF prior to any screening procedure.
- •No gender limitation, 14 years ≤ age ≤ 65 years.
- •Intention to HSCT therapy.
- •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.
- •Life expectancy ≥ 8 weeks at the time of enrollment.
- •Eastern Cooperative Oncology Group performance status score of 0 or
- •Adequate bone marrow, renal, hepatic, pulmonary and cardiac function:
- •Adequate marrow function for lymphodepletion chemotherapy assessed by the investigator.
- •Creatinine clearance \> 30 mL/min according to the Cockcroft-Gault formula;
- •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.)
Exclusion Criteria
- •Allergic to preconditioning measures.
- •History of allogeneic HSCT.
- •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.)
- •Severe active infection. (Simple urinary tract infection (UTI) and uncomplicated bacterial pharyngitis are permitted.)
- •Pulmonary embolism within 3 months prior to enrollment.
- •Severe cardiovascular and cerebrovascular diseases and hereditary diseases intolerant to CAR-T therapy assessed by the investigator prior to enrollment.
- •Presence of symptomatic CNS involvement (both primary and secondary) at screening confirmed by imaging;
- •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.)
- •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.)
- •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.
Arms & Interventions
Treatment
In this study, allogeneic anti-CD19 CAR T cells (ThisCART19A) infusion is used as a bridge therapy to hematopoietic stem cell transplantation to treat patients with refractory or relapsed CD19 positive B cell acute lymphoblastic leukemia. Lymphodepletion conditioning before CAR T cell infusion consists of fludarabine, CTX and VP-16.
Intervention: Treatment
Outcomes
Primary Outcomes
ORR
Time Frame: 4 week
Overall response rate
MRD Negativity
Time Frame: 4 week
MRD Negativity is assessed utilizing multicolor flow cytometry to detect leukemia cells with a sensitivity of 10\^ (-4).
Secondary Outcomes
- LFS(2 year)
- BFBM(2 year)
- PR(2 year)
- DOR(2 year)
- CRi(2 year)
- CR(2 year)
- CRh(2 year)
- OS(2 year)