CART19 Cells Effects in Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia and Non-Hodgkin's Lymphoma (UHKT-CAR19-01)

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.

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

Study Overview

• Status: Recruiting
• Conditions: Non-Hodgkin's Lymphoma, Relapsed; Non-Hodgkin's Lymphoma Refractory; Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia
• Intervention / Treatment: Drug: Autologous CAR19 T lymphocytes

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.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jan Vydra; Phone Number: +420221977182; Email: jan.vydra@uhk.cz
• Study Contact Backup: Name: Petr Lesny; Phone Number: +420221977629; Email: petr.lesny@uhkt.cz

Study Locations

• Czechia
  • Prague, Czechia, 12800
    • Recruiting
    • Institute of Hematology and Blood Transfusion, Czech Republic
    • Contact: Jan Vydra, MD; Phone Number: +420 221977182; Email: jan.vydra@uhkt.cz
    • Contact: Petr Lesny, MD; Phone Number: +420221977629; Email: petr.lesny@uhkt.cz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Autologous CAR19 T lymphocytes; Human Autologous T Lymphocytes Expressing the Chimeric Antigen Receptor Specific to CD19	Drug: Autologous CAR19 T lymphocytes; First-in-human trial examining the safety and efficacy of CART19 in r/r B-ALL and B-NHL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Institute of Hematology and Blood Transfusion, Czech Republic
• Investigators: Study Chair: Petr Lesny, Institute of Hematology and Blood Transfusion, Czech Republic; Principal Investigator: Jan Vydra, Institute of Hematology and Blood Transfusion, Czech Republic

Publications and helpful links

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Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2021
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): December 12, 2025

Study Registration Dates

• First Submitted: July 19, 2021
• First Submitted That Met QC Criteria: September 13, 2021
• First Posted (Actual): September 23, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 3, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: CAR T cell; ALL; Leukemia; Relapsed or Refractory; Chimeric antigen receptor; CAR; B Cell; B-NHL
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia; Lymphoma; Leukemia, Lymphoid; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: UHKT-CAR19-01; 2018-004789-32 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No