Dynamic Changes in the Levels of sCD62L and SPARC in Chronic Myeloid Leukemia Patients During Imatinib Treatment

Sponsor
Tanta University (Other)
Overall Status
Completed
CT.gov ID
NCT05387330
Collaborator
(none)
35
1
44.9
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Study Details

Study Description

Brief Summary

This study aims to monitor the levels of soluble L-selectin (sCD62L) and secreted protein acidic rich in cysteine (SPARC) in chronic phase chronic myeloid leukemia (CP-CML) patients at baseline and after three and six months of imatinib therapy and evaluated the effect of imatinib on their levels and correlated their levels to clinical and laboratory parameters.

Condition or Disease Intervention/Treatment Phase
  • Diagnostic Test: ELISA kit

Detailed Description

Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disorder characterized by the reciprocal t (9:22) chromosomal translocation. This rearrangement produces abnormal chromosome called Philadelphia chromosome carrying the chimeric BCR-ABL oncoprotein which encodes for tyrosine kinase (TK). The Break Point Cluster Region- Abelson (BCR-ABL) fusion oncoprotein activates the various downstream signaling pathways causing reduced hematopoietic cell differentiation, decreased apoptosis, enhance proliferation and survival of leukemic cells. CML remains incurable for the most part, and only allogeneic hematopoietic stem cell transplantation can eradicate and cure CML. This is probably because quiescent leukemic stem cells are resistant to tyrosine kinase inhibitors (TKIs).

Imatinib (IM) was the first tyrosine kinase inhibitor to receive approval by the Food and Drug Administration for the treatment of patients with CML-CP. It acts via competitive inhibition at the ATP - binding site of the BCR-ABL protein, which results in the inhibition of phosphorylation of proteins involved in signal transduction. It inhibits the BCR-ABL kinase.

L-selectin is a glycoprotein which is one of three members in a family of cell adhesion molecules called selectins. L-selectin is expressed on most leukocytes and it appears to play an important role in the early stages of leukocyte-endothelial cell interaction. L-selectin is a critical molecule for the leukocyte-endothelial cell interaction that results in migration of naïve T-cells into peripheral lymph nodes and inflammatory locales such as: tumor microenvironment.

Secreted Protein, Acidic Rich in Cysteine (SPARC) is a multi-functional matricellular glycoprotein with growth inhibitory and anti-angiogenic activity in some cell types. This protein has counter adhesive properties, has effects on cell shape, immune surveillance, angiogenesis and inhibits cell proliferation. SPARC is multifunctional calcium binding matricellular glycoprotein, participates in tissue remodeling, morphogenesis and bone mineralization and is secreted by different types of cells such as: osteoblasts, fibroblasts and endothelial cells. SPARC binds Vascular Endothelial Growth Factor (VEGF), preventing VEGF induced tyrosine phosphorylation of VEGFR1 and antagonizing its pro-angiogenic effects. The role of SPARC in tumor genesis appears to be cell-type specific due to its diverse function in given microenvironment.

sCD62L and SPARC analyzed using commercially available ELISA kit.

Study Design

Study Type:
Observational
Actual Enrollment :
35 participants
Observational Model:
Cohort
Time Perspective:
Prospective
Official Title:
Monitoring of Soluble L-selectin (sCD62L) and Secreted Protein Acidic Rich in Cysteine in Chronic Myeloid Leukemia Patients Treated by Imatinib
Actual Study Start Date :
Apr 1, 2018
Actual Primary Completion Date :
Jul 25, 2021
Actual Study Completion Date :
Dec 28, 2021

Arms and Interventions

Arm Intervention/Treatment
CP-CML patients

Twenty five newly diagnosed CP-CML patients. Plasma sCD62L and serum SPARC levels were measured using commercially available ELISA kits

Diagnostic Test: ELISA kit
Sandwich ELISA kit for the accurate quantitative detection of sCD62L and SPARC in human plasma and serum samples.

Control

Ten matched controls were enrolled. Plasma sCD62L and serum SPARC levels were measured using commercially available ELISA kits

Diagnostic Test: ELISA kit
Sandwich ELISA kit for the accurate quantitative detection of sCD62L and SPARC in human plasma and serum samples.

Outcome Measures

Primary Outcome Measures

  1. Dynamic changes of sCD62L and SPARC levels in CP-CML patients during imatinib treatment [Baseline and after three and six months of treatment]

    Monitoring the changes in sCD62L and SPARC levels at baseline and after three and six months of imatinib treatment

Secondary Outcome Measures

  1. Correlations of sCD62L or SPARC levels with laboratory and clinical parameters [Baseline and after three and six months of treatment]

    Correlations of sCD62L or SPARC levels with BCR-ABL1%, sokal risk score, spleen size, age and white blood cells, neutrophils, monocytes and lymphocytes counts at baseline and after three and six months of imatinib treatment

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
  • Both sexes.

  • Newly diagnosed patient with chronic phase, Philadelphia chromosome positive (Ph+) CML.

  • Age ≥ 18 years.

Exclusion Criteria:
  • Patients in blastic or accelerated phase of chronic myeloid leukemia.

  • Previous treatment with Imatinib.

  • Pregnancy and lactation.

  • Severe hepatic dysfunction.

  • Kidney dysfunction.

  • Intolerant or incompliant to imatinib.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Tanta University Tanta Egypt 31511

Sponsors and Collaborators

  • Tanta University

Investigators

  • Principal Investigator: Mahmoud M Elkholy, Bachelor, Clinical Pharmacy Department, Faculty of Pharmacy, Al Salam University in Egypt
  • Principal Investigator: Sahar M El-Haggar, Ph D, Clinical Pharmacy Department, Faculty of Pharmacy, Tanta University
  • Principal Investigator: Maryan W Fahmi, Ph D, Medical oncology unit, Internal medicine Department, Faculty of medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Mahmoud Mohamed Elkholy, Instructor of Clinical Pharmacy, Tanta University
ClinicalTrials.gov Identifier:
NCT05387330
Other Study ID Numbers:
  • 9093595
First Posted:
May 24, 2022
Last Update Posted:
May 24, 2022
Last Verified:
May 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Mahmoud Mohamed Elkholy, Instructor of Clinical Pharmacy, Tanta University
Additional relevant MeSH terms:

Study Results

No Results Posted as of May 24, 2022