Non-Hodgkin's Lymphoma Refractory, Non-Hodgkin's Lymphoma, Relapsed, Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia
Conditions
Keywords
B Cell, ALL, Relapsed or Refractory, B-NHL, Leukemia, Chimeric antigen receptor, CAR, CAR T cell
Brief summary
Phase I Dose Escalation Study of CART19 Cells for Adult Patients With Relapsed / Refractory Acute Lymphoblastic Leukemia and Non-Hodgkin's Lymphoma.
Detailed description
This is an open-label, single arm study on up to 24 adult subjects with refractory or relapsed CD19+ Non-Hodgkin's Lymphoma or B-ALL. Following lymphodepleting conditioning regimen, the patients will receive a single dose of autologous CAR19 T lymphocytes provided by the sponsor´s manufacturing facility. CART19 dose will be escalated in consecutive patients using accelerated titration design in order to establish recommended CART19 dose for further study, which will be either Maximum Tolerated Dose (MTD) or Maximum Feasible Dose (MFD), whichever is reached first.
Interventions
DRUGAutologous CAR19 T lymphocytes
First-in-human trial examining the safety and efficacy of CART19 in r/r B-ALL and B-NHL
Sponsors
Institute of Hematology and Blood Transfusion, Czech Republic
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Patient with refractory or relapsing CD19 positive B-ALL or B-NHL defined as: 1. B-ALL refractory to treatment or in the second or subsequent relapse (hematological OR molecular), OR 2. B-NHL refractory to treatment or in first relapse ineligible for autologous stem cell transplantation (ASCT) or in second to fourth relapse, OR 3. B-ALL or B-NHL relapsing after autologous or allogeneic hematopoietic cell transplantation (HCT). 2. CD19 expression on malignant cells confirmed by flow cytometry or by immunohistochemistry. 3. Age ≥18 years and ≤ 80 yearss. 4. Patient able to understand and sign informed consent. 5. Women of child-bearing potential: negative pregnancy test at enrolment (PSV) and at Visit 1. General
Exclusion criteria
1. Known hypersensitivity to any component of the Investigational Medicinal Product (IMP). 2. Autologous or allogeneic HCT in 3 months prior to IMP administration. 3. Severe, uncontrolled active infection. 4. Life expectancy \< 6 weeks. 5. Parenchymal central nervous system involvement. 6. Respiratory insufficiency (need for oxygen therapy). 7. Significant liver impairment: bilirubin \> 50 µmol/L, AST or ALT \> 4times normal upper limit. 8. Acute kidney injury with serum creatinine \> 180 µmol/L, oliguria or need for acute dialysis. 9. Heart failure with EF \< 30% by echocardiography. 10. Presence of active grade 3-4 acute GvHD. 11. Serious uncontrolled neurological comorbidity. 12. Vaccination with live virus vaccines in the 4 weeks before IMP administration and within 90 days after the IMP dose. 13. Women: pregnancy or breast-feeding. 14. Subjects of fertile age, unless permanent sexual abstinence is their lifestyle choice: * female patients of childbearing potential not willing to use a highly effective method of contraception during the study, * male patients whose sexual partner(s) are women of childbearing potential who are not willing to use a highly effective method of contraception during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events | Up to 2 years post treatment | Cumulative incidence of IMP-related adverse events (AEs) graded by ASTCT consensus grading criteria for Cytokine Release Syndrome (CRS) and Immune effector cell-associated neurotoxicity syndrome (ICANS) and by Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 for other AEs. Toxicities will be followed from the start of Blood Collection or Apheresis until the end of the study. |
| Assessment of Dose-Limiting Toxicities (DLTs) | Up to 28 days after IMP administration | Incidence of Dose-limiting toxicities (DLTs) during the first 28 days after IMP administration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete remission ( CR) rate | CR rate at 100 days and 6 months after IMP administration | Assessment of the efficacy of IMP cells administration in patients with refractory or relapsed CD19+ NHL and B-ALL evaluated by Complete Remission rate |
| Overall Survival | OS at 1 year after IMP administration | Assessment of the efficacy of IMP cells administration in patients with refractory or relapsed CD19+ NHL and B-ALL evaluated by Overall Survival |
| Quality of life using the European Organization for the Research and Treatment of Cancer 30 item questionnaire (EORTC QLQ-C30). | At 6 months and 1 year following IMP administration | EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items on a four-point scale, with 1 as not at all and 4 as very much. A change of 5 - 10 points is considered a small. A change of 10 - 20 points is considered a moderate change. |
Other
| Measure | Time frame | Description |
|---|---|---|
| CART19 cells in peripheral blood, bone marrow and cerebrospinal fluid | Up to 24 months | Assessment of quantity and phenotype of CART19 cells in peripheral blood, bone marrow and cerebrospinal fluid using using flow-cytometry |
Countries
Czechia
Contacts
Primary ContactJan Vydra
Backup ContactPetr Lesny
Outcome results
None listed