ThisCART19A Bridging to alloHSCT for R/R B-ALL
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Drug: 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.
|
Outcome Measures
Primary Outcome Measures
- ORR [4 week]
Overall response rate
- MRD Negativity [4 week]
MRD Negativity is assessed utilizing multicolor flow cytometry to detect leukemia cells with a sensitivity of 10^ (-4).
Secondary Outcome Measures
- CR [2 year]
Complete response
- CRi [2 year]
CR with incomplete hematologic recovery
- CRh [2 year]
CR with partial hematological recovery
- BFBM [2 year]
Blast-free hypoplastic or aplastic bone marrow
- PR [2 year]
Partial response
- DOR [2 year]
Duration of response
- LFS [2 year]
Leukemia-free survival
- OS [2 year]
Overall survival
Eligibility Criteria
Criteria
Inclusion Criteria:
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Voluntarily sign a documented IRB-approved ICF prior to any screening procedure.
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No gender limitation, 14 years ≤ age ≤ 65 years.
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Intention to HSCT therapy.
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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.
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Life expectancy ≥ 8 weeks at the time of enrollment.
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Eastern Cooperative Oncology Group performance status score of 0 or 1.
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Adequate bone marrow, renal, hepatic, pulmonary and cardiac function:
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Adequate marrow function for lymphodepletion chemotherapy assessed by the investigator.
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Creatinine clearance > 30 mL/min according to the Cockcroft-Gault formula;
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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.)
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Oxygen saturation (SaO2) ≥ 92% on room air.
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Cardiac function：left ventricular ejection fraction (LVEF) ≥ 40% assessed by echocardiography.
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CD19-positive leukemia obtained from bone marrow or peripheral blood confirmed by flowcytometry or biopsy during screening.
Exclusion Criteria:
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Allergic to preconditioning measures.
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History of allogeneic HSCT.
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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.)
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Severe active infection. (Simple urinary tract infection (UTI) and uncomplicated bacterial pharyngitis are permitted.)
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Pulmonary embolism within 3 months prior to enrollment.
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Severe cardiovascular and cerebrovascular diseases and hereditary diseases intolerant to CAR-T therapy assessed by the investigator prior to enrollment.
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Presence of symptomatic CNS involvement (both primary and secondary) at screening confirmed by imaging;
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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.)
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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.)
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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.
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Any conditions that would, in the investigator's assessment, increase risks in patients or interfere with the outcomes of the trial.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The First Affiliated Hospital of Soochow University | Suzhou | Jiangsu | China | 215000 |
Sponsors and Collaborators
- The First Affiliated Hospital of Soochow University
- Fundamenta Therapeutics, Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SZ4602