NCT02842320: CAR-LMC

Targeting Leukemic Stem Cell Expressing the IL-1RAP Protein in Chronic Myelogenous Leukemia (CML)

Completed NA Last updated 1 June 2022

What this trial tests

NA trial testing biological samples in Chronic Myeloid Leukemia in 53 participants. Completed in 15 July 2020.

Timeline

14 October 2015

Primary endpoint
15 July 2020

15 July 2020

Quick facts

Lead sponsor	Centre Hospitalier Universitaire de Besancon
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	other
Enrollment	53
Start date	14 October 2015
Primary completion	15 July 2020
Estimated completion	15 July 2020
Sites	4 locations across France

Drugs / interventions tested

• biological samples — full drug profile →

Conditions studied

• Chronic Myeloid Leukemia — all drugs for Chronic Myeloid Leukemia →

Sponsor

Centre Hospitalier Universitaire de Besancon

Who can join

Adults 18 to 75, any sex, with Chronic Myeloid Leukemia. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

The tyrosine kinase inhibitor therapy (iTKs) is the first-line treatment of chronic myelogenous leukemia (CML).

Its effectiveness in controlling the progression of the disease is such that it is possible today to consider stopping treatment in patients with deep molecular response (\> RM4.0).

Only in about 50% of cases, patients relapse. It has been shown in these patients that hematopoietic stem cells (HSCs) are persistant, quiescent and insensitive to iTKs. These cells are probably at the origin of relapse. It is therefore necessary to develop complementary therapies to cure the disease and consider discontinuation iTKs The development of anti-tumor immunotherapy approach using genetically modified T cells to express a chimeric antigen receptor (CAR) and specifically targeting CML CSH + could address this issue. The membrane expression of the IL-1-RAP protein could be an interesting target.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Biology and relevance of human acute myeloid leukemia stem cells.
   Thomas D, Majeti R. · · 2017 · cited 357× · PMID 28159741 · DOI 10.1182/blood-2016-10-696054
2. CAR T Cells for Acute Myeloid Leukemia: State of the Art and Future Directions.
   Mardiana S, Gill S. · · 2020 · cited 155× · PMID 32435621 · DOI 10.3389/fonc.2020.00697
3. Dysregulated haematopoietic stem cell behaviour in myeloid leukaemogenesis.
   Yamashita M, Dellorusso PV, Olson OC, Passegué E. · · 2020 · cited 128× · PMID 32415283 · DOI 10.1038/s41568-020-0260-3
4. Current updates on generations, approvals, and clinical trials of CAR T-cell therapy.
   Asmamaw Dejenie T, Tiruneh G/Medhin M, Dessie Terefe G, Tadele Admasu F, et al · · 2022 · cited 105× · PMID 36094837 · DOI 10.1080/21645515.2022.2114254
5. SRSF10-mediated IL1RAP alternative splicing regulates cervical cancer oncogenesis via mIL1RAP-NF-κB-CD47 axis.
   Liu F, Dai M, Xu Q, Zhu X, et al · · 2018 · cited 94× · PMID 29429992 · DOI 10.1038/s41388-017-0119-6
6. Current modalities in cancer immunotherapy: Immunomodulatory antibodies, CARs and vaccines.
   Lohmueller J, Finn OJ. · · 2017 · cited 64× · PMID 28322974 · DOI 10.1016/j.pharmthera.2017.03.008
7. Therapeutic Antibodies for Myeloid Neoplasms-Current Developments and Future Directions.
   Schürch CM. · · 2018 · cited 30× · PMID 29868474 · DOI 10.3389/fonc.2018.00152
8. Therapeutic targeting of the inflammasome in myeloid malignancies.
   Chakraborty S, Shapiro LC, de Oliveira S, Rivera-Pena B, et al · · 2021 · cited 29× · PMID 34521810 · DOI 10.1038/s41408-021-00547-8