CART19 Cells Effects in Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia and Non-Hodgkin's Lymphoma

• Status: Recruiting
• Trial end date: 2028-06-01
• Target enrollment: 0
• Participant gender: All

Summary

Phase I Dose Escalation Study of CART19 Cells for Adult Patients With Relapsed / Refractory Acute Lymphoblastic Leukemia and Non-Hodgkin's Lymphoma.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Institute of Hematology and Blood Transfusion, Czech Republic

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 < 65 years.

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. Vaccination with live virus vaccines in the 4 weeks before IMP administration and within 90 days after the IMP dose.

4. Women: pregnancy or breast-feeding.

5. 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 dialysis.

7. Heart failure with Ejection Fraction (EF) < 30% by echocardiography.

8. Presence of active grade 3 - 4 acute GvHD