Leukemic Stem Cell Detection for Chronic Myeloid Leukemia Patients With Major Molecular Response

NCT ID: NCT04104035

Last Updated: 2019-09-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

100 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-08-13

Study Completion Date

2021-01-31

Brief Summary

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Multi-Center, national, non-drug, prospective cohort study Target patient number is 100 The amount of CD45+/CD34+/CD38-/CD26+ levels of chronic myeloid leukemia (CML) stem cells in CML patients with and without BCR-ABL hematopoiesis will be compared.

There will be 2 arms;

1. Patients with BCR-ABL-positive hematopoiesis
2. CML patients with BCR-ABL activity inhibition under tyrosine kinase inhibitor (TKI) therapy

Detailed Description

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In the present study, its aimed to compare the amount of CD45+/CD34+/CD38-/CD26+ levels of CML stem cells in CML patients with and without BCR-ABL hematopoiesis. Therefore, the amount of CD45+/CD34+/CD38-/CD26+ levels of CML stem cells in CML patients will be analyzed using bone marrow and peripheral blood samples and whether leukemic stem cells are present in the bone marrow and at what amount, if present, although these cells are cleared from the peripheral blood, will be investigated. Additionally this study would pave the way for further cellular treatment strategies against CML stem cells, being the pioneer of development of curative treatments in CML. Until now, TKI discontinuation studies have failed in patients with long-term BCR-ABL negativity. There is a chance for cure in patients in whom the BCR-ABL status becomes negative with chimeric antigen receptor (CAR) T-cell treatment modalities which target leukemic stem cells. Also, monoclonal antibodies and/or cellular treatments targeting leukemic stem cells are the main treatment strategy is to reduce the CML treatment-related cost. In the international platform, the accurate definition of leukemic stem cell in CML and development of targeted cellular treatments have been also paid a great attention with a given priority for patent application. The primary objective of the present study is to accurately detect leukemic stem cells in CML and to estimate the threshold value for the prediction of recurrence or cure.

To the best of investigators knowledge, there is a very limited number of studies in the literature and there is no study available comparing leukemic stem cells (CD45+/CD34+/CD38-/CD26+) in patients with BCR-ABL-positive hematopoiesis and CML patients with BCR-ABL activity inhibition under TKI therapy in Turkey. Therefore,for the first time, it is planned to evaluate the prognostic value of the amount of leukemic stem cells in CML and to tailor individual treatment options.

Newly diagnosed CML patients or patients with a previous diagnosis under follow-up with or without TKIs will be included in this study. The patients will be divided into two groups as follows:

Group 1: Patients with BCR-ABL-positive hematopoiesis (newly diagnosed CML patients, CML patients with leukocytosis, CML patients without a hematological and/or cytogenetic and/or molecular response, CML patients whose BCR-ABL status becomes negative and then positive) will be included.

Group 2: Patients with CML with BCR-ABL activity inhibition under TKI therapy (patients with major molecular response (MMR) and/or deeper response) will be included.

Peripheral blood samples from 30 patients and bone marrow aspiration samples from 20 patients will be collected for each group. A total of 100 patients will be included in the study. The number of bone marrow aspiration samples is limited to 20 patients for each group, as this method is more invasive with a higher rate of complications. Peripheral blood samples will be collected simultaneously in patients in whom bone marrow samples are collected. For an accurate examination, the bone marrow samples and the peripheral blood samples will be concomitantly analyzed for each individual patient. The presence and amount of CD45+/CD34+/CD38-/CD26+ leukemic stem cells will be analyzed using multicolor flow cytometry at Ankara University, Faculty of Medicine, Ibni Sina Hospital, Hematology Lab. The peripheral blood and bone marrow samples obtained at Hacettepe University and Ege University will be transferred to Ankara University, Faculty of Medicine, Ibni Sina Hospital, Hematology Lab in accordance with the codes of the Biological Material Transfer Agreement. As bone marrow aspiration and BCR-ABL molecular testing are routinely used in the diagnosis and follow-up of CML patients, these interventions pose no additional burden for the patients.

Conditions

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Chronic Myeloid Leukemia

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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BCR-ABL-positive hematopoiesis

Patients with BCR-ABL-positive hematopoiesis (newly diagnosed CML patients, CML patients with leukocytosis, CML patients without a hematological and/or cytogenetic and/or molecular response, CML patients whose BCR-ABL status becomes negative and then positive) will be included.

No interventions assigned to this group

BCR-ABL activity inhibition under TKI

Patients with CML with BCR-ABL activity inhibition under TKI therapy (patients with MMR and/or deeper response) will be included.

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* Newly diagnosed CML patients or patients with a previous diagnosis under follow-up with TKIs

Exclusion Criteria

\-
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ankara University

OTHER

Sponsor Role lead

Responsible Party

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Osman Ilhan

Prof.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Osman Ilhan, Prof

Role: PRINCIPAL_INVESTIGATOR

Ankara University Medical Faculty Department of Hematology

Locations

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Ankara University

Ankara, , Turkey (Türkiye)

Site Status RECRUITING

Countries

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Turkey (Türkiye)

Central Contacts

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Osman Ilhan, Prof

Role: CONTACT

+905322534532

Zehra Narli

Role: CONTACT

+905556171054

Facility Contacts

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Osman Ilhan, Prof

Role: primary

Other Identifiers

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CML-BCR-ABL-TKI

Identifier Type: -

Identifier Source: org_study_id

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