Effects of CART19 Cells in Patients with Certain Blood Cancers

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.

This study is testing a new treatment using modified immune cells to see if it can help adults with certain types of blood cancers that haven't responded to other therapies.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Institute of Hematology and Blood Transfusion, Czech Republic (Academic / other)
• Drugs / interventions: Alemtuzumab, chemotherapy, methotrexate, Fludarabine
• Locations: 1 site (Prague)
• Trial ID: NCT05054257 on ClinicalTrials.gov

What this trial studies

This is a Phase I open-label, single-arm study evaluating the safety and efficacy of autologous CAR19 T lymphocytes in adult patients with relapsed or refractory CD19+ Non-Hodgkin's Lymphoma or B-cell Acute Lymphoblastic Leukemia. The study will involve up to 24 participants who will undergo a lymphodepleting conditioning regimen followed by a single dose of CART19 cells. The dose will be escalated in consecutive patients using an accelerated titration design to determine the maximum tolerated or feasible dose for further studies.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 80 with relapsed or refractory CD19 positive B-ALL or Non-Hodgkin's Lymphoma.

Not a fit: Patients with severe uncontrolled infections or those who have had recent hematopoietic cell transplantation may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat blood cancers.

How similar studies have performed: Other studies using CAR T-cell therapies have shown promising results, indicating potential success for this approach.

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.

Where this trial is running

Prague

• Institute of Hematology and Blood Transfusion, Czech Republic — Prague, Czechia (Recruiting)

Study contacts

• Principal investigator: Jan Vydra — Institute of Hematology and Blood Transfusion, Czech Republic
• Study coordinator: Jan Vydra

Conditions Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia; Non-Hodgkin's Lymphoma Refractory; Non-Hodgkin's Lymphoma, Relapsed; B Cell; ALL; Relapsed or Refractory; B-NHL; Leukemia