Unravelling the Role of KCTD Protein Family in the Clinical Management of Childhood Acute Lymphoblastic Leukemias

March 22, 2024 updated by: IRCCS SYNLAB SDN
A transcriptomic analysis of bone marrow from B-ALL patients was performed by our research group for identifying novel protein/factor with a putative role of disease biomarker. Along with some already known B-ALL biomarkers, our analysis highlighted deregulation of some members of an emerging protein class denoted as KCTD (Potassium ChannelTetramerization Domain-containing proteins). Starting from our preliminary observations, and considering that KCTDs havenever been studied in ALL, we decided to study these proteins in B- and T-ALL affected pediatric patients, enrolled by our research group in collaboration with AORN Santobono-Pausilipon pediatric oncological hospital.Indeed, the present research program aims at opening a new scenario for the study of KCTD proteins in childhood leukemias. The final goal of the project will be to evaluate the translational relevance of selected deregulated KCTDs as novel biomarkers useful for B-ALL and T-ALL diagnostics, and patient management.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

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Intervention / Treatment

Intervention / Treatment

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Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
80

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

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Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

1 year to 18 years (Child, Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

The study foresees the possibility of recruiting approximately 60 patients with B-ALL and 15-20 patients with T-ALL. Furthermore, control subjects with age and sex comparable to those of the patients will be recruited. Finally, about 100 units of cord blood that do not meet the criteria for therapeutic cryopreservation and for which consent has been given for their use for scientific research will be used

Description

Inclusion Criteria:

  • Patients aged 1-18 years of both sexes diagnosed with B- ALL and T-ALL;
  • Patients who will have signed the informed consent

Exclusion Criteria:

  • Patients who refuse to participate in the study;
  • Patients who do not fall within the age range mentioned above

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Pediatric acute lymphoblastic leukemia patients
pediatric patients of 1-16 years old affected by acute lymphoblastic leukemia
Other: observational study
analysis of biomarkers of interest (DNA-RNA and proteins) in MNC purified from the subjects' blood
healthy subjects
cord blood from healthy donors that cannot be used for clinical purposes
Other: observational study
analysis of biomarkers of interest (DNA-RNA and proteins) in MNC purified from the subjects' blood

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
KCTD expression levels, by RNAseq approach, in a cohort of B and T cell ALL affected patients compared to unaffected controls
Time Frame: 1-12 months
We enroll during this project about 15-20 B-ALL, and 3-6 T-ALL patients.RNAseq experiments for transcriptome analysis will be performed on a study cohort of at least 8 B-ALL patients, 3-4 T-ALL patients, and naive B or T cells purified from cord blood as control for B- and T-ALL correspondingly. Raw counts will be used and an empirical Bayes approach applied (DESeq2, R package). The results will include, for each gene, log-fold change (log2), base mean, p-value and adjusted p-values (Benjamimi-Hochberg). DEgenes output will be exported into format suitable for IPA Ingenuity pathway AnalysisSoftware (Qiagen), for gene annotations, functional analysis and biomarker prediction. The KCTD proteins that will be dereguleted in B-ALL and T-ALL will be studied in detail.
1-12 months
RT-PCR validation of deregulated KCTDs and identification of possible KCTDs interactors in leukemia by functional proteomic approach
Time Frame: 13-24 months
After the interpretation of transcriptome data we will perform specific validation experiments by reat-time pcr, westernblotting, flow cytometry and microscopy. Briefly,total RNA will be purified from about 5e6 total MNC and used for RT-PCR experiments; BM smear will be collected for immunofluorescence analysis of deregulated KCTDs; protein total extract will be obtained from at least 1 e 6 total MNC and stored at -80°C until Western Blotting; finally, live mononuclear cells will be treted for permeabilization and cytoplasmic immunostaining of the KCTDs of interest. All experiments will be settled-up on B- and T-ALL in vitro human model systems and then performed on patients and controls cells. Moreover, in order to identify possible interactors of KCTDs proteins we will use B-ALL and T-ALL cell lines for functional proteomics analysis.
13-24 months
Correlation of B-ALL patients clinical data with KCTDs expression level
Time Frame: 25-36 months
Firstly, we will evaluated the usefulness of the deregulated KCTD proteins as novel markers of leukemia to be tested by multiparametric clinical flowcytometry. A specific protocol has been already setted-up by our research team, and it is able to stain cytoplasmicantigens (such as KCTD proteins) with surface antigens commonly used for to study hematoogical compartments by flowcytometry. This approach will be useful especially in monitoring patient response to treatment as well as detection of minimal residual disease. Moreover, being able to detect cytoplasmic KCTDs in combination with surface antigens, we planned to describe the KCTDs expression levels in multiple cellular population residing in marrow and peripheral blood.Secondly, the overall data obtained in this study will be also interpreted looking at the patient clinics with particular reference to the response to therapy, the risk of relapse and, when possible, resistance to therapy.
25-36 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
IRCCS SYNLAB SDN

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Santobono-Pausilipon Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 2, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2024

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 31, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 27, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 6, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 15, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 22, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 5/19

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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