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

Summary

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

Eligibility

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.

Conditions4

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