Assessment of Safety and Efficacy of ThisCART19A in Adult Patients With B Cell Malignancies After Failure of Autologous Chimeric Antigen Receptor T- Cell(CAR-T) Therapy
Study Details
Study Description
Brief Summary
This is a a phase 1, open label study to assess the safety and efficacy of ThisCART19 (Allogeneic CAR-T targeting CD19) in adult patients with B cell malignancies after failure of autologous chimeric antigen receptor T- cell(CAR-T) therapy in china.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
This is a phase 1, single-center, nonrandomized, open-label, dose-escalation and dose expansion study to evaluate the safety and efficacy of ThisCART19A in adult patients with B cell malignancies after failure of autologous chimeric antigen receptor T- cell(CAR-T) therapy and identify a treatment regimen most likely to result in clinical efficacy while maintaining a favorable safety profile.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: ThisCART19A cells infusion In this study, allogeneic anti-CD19 CAR T cell (ThisCART19A) infusion is used to treat patients with refractory or relapsed CD19 positive B cell acute lymphoblastic leukemia. |
Drug: ThisCART19A
ThisCART19A is a new type CAR-T therapy for patients with r/r B Cell Malignancy .
Drug: Fludarabine Pill
Fludarabine is used for lymphodepletion.
Drug: Cyclophosphamide
Cyclophosphamide is used for lymphodepletion.
Drug: VP-16 Protocol
VP-16 is used for lymphodepletion.
|
Outcome Measures
Primary Outcome Measures
- Dose limited toxicity(DLT) observation in patient with B Cell Malignancy in each dose level during dose escalation stage [28 days]
DLT is defined as the incidence of severe adverse events related to ThisCART19A more than 33% in each dose level.
- Objective Response Rate within 3 months during dose expansion stage [3 months]
For Acute Lymphoblastic Leukemia (ALL), Objective response rate(ORR) is the percentage of patients who achieve Complete Response (CR) or Complete Response With Incomplete Hematologic Recovery (CRi); for lymphoma, ORR is the incidence of either a complete response (CR) or a partial response (PR).
- Minimum Residual Disease (MRD) Negative Remission Rate within 3 months during dose expansion stage [3 months]
MRD was assessed utilizing multicolor flow cytometry to detect residual cancerous cells with a sensitivity of 10^-4. MRD negative remission was defined as MRD < 10^-4 threshold. Percentage of participants with MRD negative remission was reported.
Secondary Outcome Measures
- Duration of response(DOR) during dose escalation stage and expansion stage [24 months]
DOR was defined as the time from first CR/CRi or PR to relapse or any death in the absence of documented relapse.
- Relapse-free Survival (RFS) [24 months]
RFS is defined as the time from the date of ThisCART19A infusion to the date of disease relapse or death from any cause.
- Event-free Survival (EFS) [24 months]
EFS is defined as the time from the date of ThisCART19A infusion to the date of disease relapse, progression, genetic relapse or death from any cause.
- Overall Survival (OS) [24 months]
OS is defined as the time from the date of ThisCART19A infusion to the date of death from any cause.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patient with relapsed or refractory acute lymphocytic leukemia, or lymphoma；
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No gender limitation, Age 14 years to 75 years (both upper and lower limits included)；
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Failing to autologous CAR-T therapy；
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Should be confirmed Cluster of differentiation(CD)19 positive；
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The expected survival time is ≥12 weeks;
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ECOG score 0-1;
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Measurable or detectble disease at time of enrollment.
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Adequate bone marrow, renal, hepatic, pulmonary and cardiac function；
Exclusion Criteria:
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Allergic to preconditioning measures；
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Patients with other malignancies other than B-cell malignancies within 5 years prior to screening. Patients with cured skin squamous carcinoma, basal carcinoma, non-primary invasive bladder cancer, localized low-risk prostate cancer, in situ cervical/breast cancer can be recruited；
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Uncontrollable bacterial, fungal and viral infection during screening；
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Patients had pulmonary embolism (PE) and/or deep vein thrombosis (DVT) within 3 months prior to enrollment;
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Had intolerant severe cardiovascular and cerebrovascular diseases and hereditary diseases prior to enrollment；
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The presence of central nervous system involvement；
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Active hepatitis B virus (HBV) or hepatitis C virus (HCV) or Human immunodeficiency virus (HIV) or Syphilis infection. HBV-DNA < 2000 IU/mL can be enrolled, but should admitted to use anti-virus drugs such as entecavir, tenofovir, etc, and supervisory the relative indication during the treatment；
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Had big lesion(single lesion diameter ≥10 cm)；
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Receive allogeneic hematopoietic stem cell transplantation less than 100 days；
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Vaccinated with influenza vaccine within 2 weeks prior to cleansing (SARS-COV19 can be included, inactivated, live/non-live adjuvant vaccinations allowed to be included)；
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Patients who are receiving GvHD treatment; Patients without GvHD and who had stopped immunosuppressive drugs for at least 1 month were eligible for inclusion；
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Women who are in pregnant or lactating, and female subjects or partners who plan to be pregnant within 1 year after cell infusion. Male subjects who plan pregnancy within 1 year after infusion.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Henan cancer hospital | Zhengzhou | Henan | China |
Sponsors and Collaborators
- Henan Cancer Hospital
- Fundamenta Therapeutics, Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ThisCART19A （FT400-011）