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Recruiting NCT05054257

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

Phase I Interventional Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia Non-Hodgkin's Lymphoma Refractory Non-Hodgkin's Lymphoma, Relapsed

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Autologous CAR19 T lymphocytes.
Who it may be relevant to
Registry conditions: Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia, Non-Hodgkin's Lymphoma Refractory, Non-Hodgkin's Lymphoma, Relapsed. Basic parameters: 18 years — 80 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
Czechia
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

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.

Overview

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

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.

Interventions

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

Primary outcome measures

  • Incidence of adverse events [Time frame: Up to 2 years post treatment]
  • Assessment of Dose-Limiting Toxicities (DLTs) [Time frame: Up to 28 days after IMP administration]
Secondary outcome measures (3)
  • Complete remission ( CR) rate [Time frame: CR rate at 100 days and 6 months after IMP administration]
  • Overall Survival [Time frame: 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). [Time frame: At 6 months and 1 year following IMP administration]

Eligibility criteria

Inclusion criteria

  • Patient with refractory or relapsing CD19 positive B-ALL or B-NHL defined as:
  • B-ALL refractory to treatment or in the second or subsequent relapse (hematological OR molecular), OR
  • B-NHL refractory to treatment or in first relapse ineligible for autologous stem cell transplantation (ASCT) or in second to fourth relapse, OR
  • B-ALL or B-NHL relapsing after autologous or allogeneic hematopoietic cell transplantation (HCT).
  • CD19 expression on malignant cells confirmed by flow cytometry or by immunohistochemistry.
  • Age ≥18 years and ≤ 80 yearss.
  • Patient able to understand and sign informed consent.
  • Women of child-bearing potential: negative pregnancy test at enrolment (PSV) and at Visit 1.

General Exclusion Criteria:

  • Known hypersensitivity to any component of the Investigational Medicinal Product (IMP).
  • Autologous or allogeneic HCT in 3 months prior to IMP administration.
  • Severe, uncontrolled active infection.
  • Life expectancy < 6 weeks.
  • Parenchymal central nervous system involvement.
  • Respiratory insufficiency (need for oxygen therapy).
  • Significant liver impairment: bilirubin > 50 µmol/L, AST or ALT > 4times normal upper limit.
  • Acute kidney injury with serum creatinine > 180 µmol/L, oliguria or need for acute dialysis.
  • Heart failure with EF < 30% by echocardiography.
  • Presence of active grade 3-4 acute GvHD.
  • Serious uncontrolled neurological comorbidity.
  • Vaccination with live virus vaccines in the 4 weeks before IMP administration and within 90 days after the IMP dose.
  • Women: pregnancy or breast-feeding.
  • 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

  • Severe uncontrolled active infection.
  • Positive test results for HIV1/2, Hepatitis B/C and lues.
  • 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

  • Severe, uncontrolled active infections.
  • Life expectancy < 6 weeks.
  • Parenchymal central nervous system involvement
  • Respiratory insufficiency (need for oxygen therapy).
  • Significant liver impairment: bilirubin > 50 µmol/L, Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) > 4times normal upper limit.
  • Acute kidney injury with serum creatinine > 180 µg/L, oliguria or need for acute dialysis.
  • Heart failure with Ejection Fraction (EF) < 30% by echocardiography.
  • Presence of active grade 3 - 4 acute GvHD
  • Serious uncontrolled neurological comorbidity.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
N/A
Model
Single group
Masking
Open label
Primary purpose
Treatment

Study locations

Czechia · 1 center
  • Institute of Hematology and Blood Transfusion, Czech Republic — Prague

Publications

  • Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, Chew A, Gonzalez VE, Zheng Z, Lacey SF, Mahnke YD, Melenhorst JJ, Rheingold SR, Shen A, Teachey DT, Levine BL, June CH, Porter DL, Grupp SA. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014 Oct 16;371(16):1507-17. doi: 10.1056/NEJMoa1407222. PMID 25317870
  • Porter DL, Hwang WT, Frey NV, Lacey SF, Shaw PA, Loren AW, Bagg A, Marcucci KT, Shen A, Gonzalez V, Ambrose D, Grupp SA, Chew A, Zheng Z, Milone MC, Levine BL, Melenhorst JJ, June CH. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med. 2015 Sep 2;7(303):303ra139. doi: 10.1126/scitranslmed.aac5415. PMID 26333935
  • Hartmann J, Schussler-Lenz M, Bondanza A, Buchholz CJ. Clinical development of CAR T cells-challenges and opportunities in translating innovative treatment concepts. EMBO Mol Med. 2017 Sep;9(9):1183-1197. doi: 10.15252/emmm.201607485. PMID 28765140
  • Hamada M, Nishio N, Okuno Y, Suzuki S, Kawashima N, Muramatsu H, Tsubota S, Wilson MH, Morita D, Kataoka S, Ichikawa D, Murakami N, Taniguchi R, Suzuki K, Kojima D, Sekiya Y, Nishikawa E, Narita A, Hama A, Kojima S, Nakazawa Y, Takahashi Y. Integration Mapping of piggyBac-Mediated CD19 Chimeric Antigen Receptor T Cells Analyzed by Novel Tagmentation-Assisted PCR. EBioMedicine. 2018 Aug;34:18-26. d PMID 30082227
  • Tipanee J, VandenDriessche T, Chuah MK. Transposons: Moving Forward from Preclinical Studies to Clinical Trials. Hum Gene Ther. 2017 Nov;28(11):1087-1104. doi: 10.1089/hum.2017.128. Epub 2017 Aug 22. PMID 28920716
  • Kebriaei P, Singh H, Huls MH, Figliola MJ, Bassett R, Olivares S, Jena B, Dawson MJ, Kumaresan PR, Su S, Maiti S, Dai J, Moriarity B, Forget MA, Senyukov V, Orozco A, Liu T, McCarty J, Jackson RN, Moyes JS, Rondon G, Qazilbash M, Ciurea S, Alousi A, Nieto Y, Rezvani K, Marin D, Popat U, Hosing C, Shpall EJ, Kantarjian H, Keating M, Wierda W, Do KA, Largaespada DA, Lee DA, Hackett PB, Champlin RE, PMID 27482888
  • Otahal P, Prukova D, Kral V, Fabry M, Vockova P, Lateckova L, Trneny M, Klener P. Lenalidomide enhances antitumor functions of chimeric antigen receptor modified T cells. Oncoimmunology. 2015 Dec 3;5(4):e1115940. doi: 10.1080/2162402X.2015.1115940. eCollection 2016 Apr. PMID 27141398
  • Yusa K, Zhou L, Li MA, Bradley A, Craig NL. A hyperactive piggyBac transposase for mammalian applications. Proc Natl Acad Sci U S A. 2011 Jan 25;108(4):1531-6. doi: 10.1073/pnas.1008322108. Epub 2011 Jan 4. PMID 21205896

Identifiers

NCT: NCT05054257 · UHKT-CAR19-01 · 2018-004789-32

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗