Relapsed or refractory B cell malignancies B-ALL CAR-T cells Cell Therapy
Conditions
Interventions
GNPTCD19SPA-0001 is an allogeneic CD19 CAR T cell product that is produced locally in Thailand. The plasmid containing the CD19 CAR was produced using two plasmids (CAR-CD19-TM28-Z and CAR-PSCACD28TM-
Experimental Biological/Vaccine
GNPTCD19SPA-0001
Sponsors
Genepeutic Bio, Co., Ltd
Eligibility
Sex/Gender
All
Age
3 Years to 39 Years
Inclusion criteria
Inclusion criteria: Participants need to fulfill all the following inclusion criteria to be included in this study. 1) Be between 3 - less than 40 years and diagnosed with B-ALL, 2) Has an identified matched allogeneic or haploidentical HSC donor, 3) Bone Marrow result demonstrating: Relapsed or refractory disease at one of the following levels: a. BM Blasts less than 5% but MRD positive b. BM Blasts more than or equal 5% but less than or equal 20%, Blast count on BM film (BM smears) will be read by a Thai Board-Certified Haematologist or a Thai Board-certified Paediatric haematologist (either PI or Sub-I of each site). The medical monitor will re-read and confirm the results of the smears. MRD assessment is performed through flow cytometry. Note: BM Blast less than or equal 20% or MRD positive will only be inclusion criteria at screening. This criterion does not apply at pre-lymphodepletion. Therefore, participants who previously had BM Blast less than or equal 20% or MRD positive at screening but have MRD negative at pre-lymphodepletion could be included in the trial. 4) All tests below must be met: a. Glomerular Filtration Rate (GFR) less than 60 mL/min/1.73 m2 or serum creatinine less than 1.0 mg/dL (or within normal ranges according to age and sex) b. Aspartate transaminase (AST) Alanine aminotransferase (ALT) less than 5 times the upper limit of the institutional normal ranges c. Bilirubin less than 2.0 mg/dL d. Pulse oxygenation more than or equal 95% on room air e. Left Ventricular Ejection Fraction (LVEF) more than or equal 45% by echocardiogram during the screening period and prior to the start of treatment, 5) Have a life expectancy of more than 12 weeks at the time of screening, 6) Have access to T cells from their matched related or haploidentical donor, 7) Hematologic parameters must meet the following: a. Hemoglobin more than or equal 7.0 g/dL; b. Platelets more than or equal 20,000/mm3 without transfusion support; c. Absolute neutrophil count (ANC) more than or equal 500/mm3 without growth factor support; d. No active hemolytic anemia; and e. No active coagulopathy, 8) Karnofsky (age more than or equal 16 years) or Lansky (age less than 16 years) score of more than or equal 50%, 9) No restrictive pulmonary disease as measured by FEV1/FVC ratio or if this cannot be done, respiratory exam, chest radiograph, and pulse oximetry as per the investigator judgement, 10) The patient or their legally authorized representative has understood the contents of the patient informed consent, and signed and dated the consent form voluntarily prior to all study procedures, 11) Are able to comply with study procedures and be available for all study visits, 12) Male participants should agree to not donate sperm during study period (i.e. up to 2.5 years following administration of GNPTCD19SPA-0001), 13) Male and female participants with reproductive potential must agree to use medically approved contraceptives from when they consent to the study until 12 months after administration of GNPTCD19SPA-0001.
Exclusion criteria
Exclusion criteria: Participants who meet any of the following exclusion criteria are NOT eligible for this study. 1) CD19 negative disease, 2) Relapse of the disease in other parts of the body (i.e. extramedullary relapse), 3) Detection of blast cells in the cerebrospinal fluid less than 28 days prior to the commencement of the study or displaying neurological abnormalities that may be associated with metastasis such as seizure, weakness or cranial nerve palsies on screening or prior to infusion of GNPTCD19SPA-0001 (chemotherapy given to patients to prevent disease from metastasizing is not considered as an exclusion criteria), 4) Diagnosed with chronic graft versus host disease (cGvHD) AND currently receiving immunosuppressive therapy, 5) Uncontrolled diabetes mellitus, 6) Organ transplant recipients (other than HSC), 7) Female participants who are pregnant, plan to become pregnant or return a positive serum human chorionic gonadotropin (beta-HCG) pregnancy test at screening, 8) Female participants who are breast feeding or planning to do so for the duration of the study, 9) Participants with a history of clinically significant physical or psychiatric conditions, unstable chronic or acute disease, or physical findings that in the opinion of the investigator may increase the risk of exposure to the investigational agent, compromise the safety of the participant, or interfere with any aspect of study conduct or interpretation of results, 10) Active, uncontrolled infection, including syphilis, hepatitis B, hepatitis C or human immunodeficiency virus (HIV), 11) Planning to travel out of the country during the study period, 12) History of alcohol or drug abuse that in the opinion of the investigator could affect the participant safety or compliance with study, 13) Any vaccination against infectious disease(s) (e.g., influenza, varicella, COVID-19) less than 6 weeks (42 days) of initiation of study treatment (Day 0), 14) Prior treatment with immunotherapy directly targeting T-cells (except anti-thymocyte globulin (ATG)), CD19-directed antibody-based therapies (except blinatumomab), or other gene therapy products, 15) Received any investigational drug or investigational anti-cancer therapy within 30 days prior to receiving GNPTCD19SPA-0001 (Day 0), 16) Concurrent participation in another therapeutic clinical trial. 17) Known allergy to albumin, dimethyl sulfoxide, cyclophosphamide or fludarabine.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Type and frequency of adverse events (AEs) and serious AE (SAEs), Level of cytokines, Overall response rate (ORR), Level of Minimal residual disease (MRD) 28 days (+/- 2) after treatment Descriptive and correlation statistics | — |
Secondary
| Measure | Time frame |
|---|---|
| Relapsed free rate/Event free survival, Overall survival rate, Duration of remission, Level of blast cells 42 days (+/- 7) after treatment Statistics tests for continuous variables (e.g., paired t-test, Analysis of Variance) and for categorical variables (e.g., McNemar's test, Wilcoxon signed-rank test) and descriptive statistics | — |
Countries
Thailand
Contacts
Public ContactKitipong Uaesoontrachoon
Genepeutic Bio., Co., LTD
Outcome results
None listed