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

Non-Hodgkin's Lymphoma, Relapsed Clinical Trial

— UHKT-CAR19-01  

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05054257
• Other study ID #: UHKT-CAR19-01
• Secondary ID: 2018-004789-32
• Status: Recruiting
• Phase: Phase 1
• Start date: June 2, 2021
• Est. completion date: June 1, 2025

Study information

• Verified date: September 2023
• Source: Institute of Hematology and Blood Transfusion, Czech Republic
• Contact: Jan Vydra
• Phone: +420221977182
• Email: jan.vydra[@]uhk.cz
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: June 1, 2025
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

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.

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, Non-Hodgkin
• Non-Hodgkin's Lymphoma Refractory
• Non-Hodgkin's Lymphoma, Relapsed
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia

Intervention

Drug:
• Autologous CAR19 T lymphocytes
First-in-human trial examining the safety and efficacy of CART19 in r/r B-ALL and B-NHL

Locations

Country	Name	City	State
Czechia	Institute of Hematology and Blood Transfusion, Czech Republic	Prague

Sponsors (1)

Lead Sponsor	Collaborator
Institute of Hematology and Blood Transfusion, Czech Republic

Country where clinical trial is conducted

Czechia, 

References & Publications (42)

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* Note: There are 42 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	CART19 cells in peripheral blood, bone marrow and cerebrospinal fluid	Assessment of quantity and phenotype of CART19 cells in peripheral blood, bone marrow and cerebrospinal fluid using using flow-cytometry	Up to 24 months
Primary	Incidence of adverse events	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.	Up to 2 years post treatment
Primary	Assessment of Dose-Limiting Toxicities (DLTs)	Incidence of Dose-limiting toxicities (DLTs) during the first 28 days after IMP administration	Up to 28 days after IMP administration
Secondary	Complete remission ( CR) rate	Assessment of the efficacy of IMP cells administration in patients with refractory or relapsed CD19+ NHL and B-ALL evaluated by Complete Remission rate	CR rate at 100 days and 6 months after IMP administration
Secondary	Overall Survival	Assessment of the efficacy of IMP cells administration in patients with refractory or relapsed CD19+ NHL and B-ALL evaluated by Overall Survival	OS at 1 year after IMP administration
Secondary	Quality of life using the European Organization for the Research and Treatment of Cancer 30 item questionnaire (EORTC QLQ-C30).	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.	At 6 months and 1 year following IMP administration