Allogeneic, CAR-T, Protein Sequestration, Non-gene Edited
Conditions
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.
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.
Interventions
DRUGThisCART19A
ThisCART19A is a new type CAR-T therapy for patients with r/r B Cell Malignancy .
DRUGFludarabine Pill
Fludarabine is used for lymphodepletion.
DRUGCyclophosphamide
Cyclophosphamide is used for lymphodepletion.
DRUGVP-16 Protocol
VP-16 is used for lymphodepletion.
Sponsors
Fundamenta Therapeutics, Ltd.
Henan Cancer Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Patient with relapsed or refractory acute lymphocytic leukemia, or lymphoma； 2. No gender limitation, Age 14 years to 75 years (both upper and lower limits included)； 3. Failing to autologous CAR-T therapy； 4. Should be confirmed Cluster of differentiation(CD)19 positive； 5. The expected survival time is ≥12 weeks; 6. ECOG score 0-1; 7. Measurable or detectble disease at time of enrollment. 8. Adequate bone marrow, renal, hepatic, pulmonary and cardiac function；
Exclusion criteria
1. Allergic to preconditioning measures； 2. 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； 3. Uncontrollable bacterial, fungal and viral infection during screening； 4. Patients had pulmonary embolism (PE) and/or deep vein thrombosis (DVT) within 3 months prior to enrollment; 5. Had intolerant severe cardiovascular and cerebrovascular diseases and hereditary diseases prior to enrollment； 6. The presence of central nervous system involvement； 7. 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； 8. Had big lesion(single lesion diameter ≥10 cm)； 9. Receive allogeneic hematopoietic stem cell transplantation less than 100 days； 10. 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)； 11. Patients who are receiving GvHD treatment; Patients without GvHD and who had stopped immunosuppressive drugs for at least 1 month were eligible for inclusion； 12. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
Countries
China
Contacts
Primary ContactKeshu zhou, Dr.
Backup ContactJun Li, Ph.D
Outcome results
None listed