Clinical trial NCT05054257: CART19 Cells Effects in Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia and Non-Hodgkin's Lymphoma
Official title: Safety and Efficacy of Anti-CD19 Chimeric Antigen Receptor-modified Autologous T Cells (CART19) in Patients with Relapsed/refractory CD19+ Acute Lymphoblastic Leukemia and Non-Hodgkin's Lymphoma. a Dose Escalation, Open-label, Phase I Study.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia
Non-Hodgkin's Lymphoma Refractory
Non-Hodgkin's Lymphoma, Relapsed
Keywords: B Cell
ALL
Relapsed or Refractory
B-NHL
Leukemia
Chimeric antigen receptor
CAR
CAR T cell
Lead sponsor: Institute of Hematology and Blood Transfusion, Czech Republic
Sponsor class: OTHER
First posted: 2021-09-23
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Exclusion criteria to Procurement of IMP manufacture starting material

1. Severe uncontrolled active infection.
2. Positive test results for HIV1/2, Hepatitis B/C and lues.
3. Concurrent or recent prior therapies before apheresis:

   * Autologous or allogeneic hematopoietic cell transplantation within 12 weeks.
   * Clofarabine, Fludarabine, Alemtuzumab within 8 weeks.
   * Donor lymphocyte infusions within 4 weeks.
   * Pegylated asparaginase within 4 weeks.
   * Maintenance chemotherapy within 2 weeks.
   * Long-acting Granulocyte Colony Stimulating Factor (G-CSF) within 2 weeks.
   * Vincristine within 2 weeks.
   * Intrathecal methotrexate within 1 week.
   * Granulocyte Colony Stimulating Factor (G-CSF) within 5 days.
   * Therapeutic dose of corticosteroids within 3 days.
   * Short-acting cytostatics within 3 days

Exclusion criteria to IMP administration

1. Severe, uncontrolled active infections.
2. Life expectancy \< 6 weeks.
3. Parenchymal central nervous system involvement
4. Respiratory insufficiency (need for oxygen therapy).
5. Significant liver impairment: bilirubin \> 50 µmol/L, Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) \> 4times normal upper limit.
6. Acute kidney injury with serum creatinine \> 180 µg/L, oliguria or need for acute dialysis.
7. Heart failure with Ejection Fraction (EF) \< 30% by echocardiography.
8. Presence of active grade 3 - 4 acute GvHD
9. Serious uncontrolled neurological comorbidity.

Primary outcomes:
measure: Incidence of adverse events
timeFrame: Up to 2 years post treatment
measure: Assessment of Dose-Limiting Toxicities (DLTs)
timeFrame: Up to 28 days after IMP administration
Secondary outcomes:
measure: Complete remission ( CR) rate
timeFrame: CR rate at 100 days and 6 months after IMP administration
measure: Overall Survival
timeFrame: OS at 1 year after IMP administration
measure: Quality of life using the European Organization for the Research and Treatment of Cancer 30 item questionnaire (EORTC QLQ-C30).
timeFrame: At 6 months and 1 year following IMP administration
Other outcomes:
measure: CART19 cells in peripheral blood, bone marrow and cerebrospinal fluid
timeFrame: Up to 24 months
Locations:
city: Prague
country: Czechia
facility: Institute of Hematology and Blood Transfusion, Czech Republic
Study officials:
affiliation: Institute of Hematology and Blood Transfusion, Czech Republic
name: Petr Lesny
role: STUDY_CHAIR
affiliation: Institute of Hematology and Blood Transfusion, Czech Republic
name: Jan Vydra
role: PRINCIPAL_INVESTIGATOR
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