Asciminib as Maintenance Treatment After Cellular Therapies for Adults With Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

June 18, 2025 updated by: City of Hope Medical Center

Pilot Study of Asciminib as a Maintenance Treatment Post Cellular Therapies in Adults With Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

This phase I trial tests the safety, side effects and best dose of asciminib as maintenance treatment for adults with Philadelphia chromosome positive acute lymphoblastic leukemia (ALL) who have undergone cellular therapies such as hematopoietic stem cell transplantation (HSCT) or chimeric antigen receptor (CAR) T cell therapy. Maintenance treatment is given to help keep cancer from coming back after it has disappeared following initial therapy. Asciminib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving asciminib may be safe and tolerable as maintenance treatment for adult patients with Philadelphia chromosome positive ALL who have undergone cellular therapies.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

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.

Detailed Description

PRIMARY OBJECTIVES:

I. Evaluate the safety of asciminib maintenance in adults with Philadelphia chromosome (Ph)+ acute lymphoblastic leukemia (ALL) in morphological complete remission (CR) post hematopoietic stem cell transplantation (HSCT; Arm 1) or chimeric antigen receptor (CAR) T cell therapy (Arm 2).

II. Determine the recommended phase 2 dosing (RP2D) of asciminib maintenance post cellular therapies in Ph+ ALL in each arm.

SECONDARY OBJECTIVES:

I. Evaluate feasibility of asciminib maintenance measured as the number of patients who continue asciminib > 3 cycles post cellular therapy.

II. Duration of response. III. Timing for minimal residual disease (MRD) and full relapse. IV. Relapse free survival at 1 year post cellular therapy. V. Overall survival at 1 year post cellular therapy. VI. Non-relapse mortality at 1 year post cellular therapy. VII. Relapse at 1 year post cellular therapy. VIII. Rates of asciminib discontinuation and interruption due to toxicity at 1 year post cellular therapy.

IX. Rate of switching to another tyrosine kinase inhibitor (TKI) at 1 year post cellular therapy X. Rate and grade of acute graft-versus-host disease (GVHD) at 180 days post initiation of asciminib maintenance post HSCT. (Arm 1) XI. Rate and grade of chronic GVHD at 1 year post initiation of asciminib maintenance post HSCT. (Arm 1) XII. GVHD-free, relapse-free survival (GRFS) at 1 year post HSCT. (Arm 1)

EXPLORATORY OBJECTIVES:

I. For patients who are MRD-negative, evaluate MRD relapse by clonoSEQ during therapy.

II. Evaluate immune cell populations and immune reconstitution post-transplant during asciminib therapy.

III. Evaluate the impact of prevalent BCR-ABL mutations and treatment emergent BCR-ABL mutations.

IV. Evaluate B-cell aplasia and CAR T cell persistence during asciminib therapy. (Arm 2) V. Quality of life assessments using Patient Reported Outcomes Measurement Information System (PROMIS).

OUTLINE: This is a dose-escalation study of asciminib followed by a dose-expansion study.

Patients receive asciminib orally (PO) once daily (QD) or twice daily (BID) on days 1-28 of each cycle. Cycles repeat every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography during screening and as clinically indicated, and bone marrow biopsy, bone marrow aspirate and blood sample collection throughout the study.

After completion of study treatment, patients are followed up at 30 days then every 3 months for 1 year.

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.
Interventional

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.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

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

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010
        • City of Hope Medical Center
        • Principal Investigator:
          • Ibrahim Aldoss
        • Contact:

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • PRE-SCREENING: Documented informed consent of the participant and/or legally authorized representative
  • PRE-SCREENING: Age ≥ 18 years
  • PRE-SCREENING: Participant was diagnosed with Ph+ ALL according to World Health Organization criteria. The BCR::ABL1 translocation may be detected by fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR), next generation sequencing (NGS), or cytogenetics at least once any time prior to cellular therapy. Participants may have p190 or p220 isoform, and participants with T315I mutation are not excluded

  • PRE-SCREENING: Participant meets one of the following criteria:

    • Arm 1: Have a date for HSCT scheduled within the next 30 days or have received HSCT within the last 30 days. Note: all HSCT donors, conditioning regimens, and GVHD prophylaxis regimens will be acceptable.
    • Arm 2: Have a date for CAR T cell infusion scheduled within the next 30 days or have received CAR T cell infusion within the last 30 days
  • PRE-SCREENING: History of pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis
  • PRE-SCREENING: History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent

  • PATIENTS AFTER DAY +30 FOLLOWING CELLULAR THERAPY: Documented informed consent of the participant and/or legally authorized representative.

    • Assent, when appropriate, will be obtained per institutional guidelines
  • PATIENTS AFTER DAY +30 FOLLOWING CELLULAR THERAPY: Eastern Cooperative Oncology Group (ECOG) ≤ 2

  • PATIENTS AFTER DAY +30 FOLLOWING CELLULAR THERAPY: Participant is between day +30 and +150 after one of the following cellular therapies:

    • Arm 1: HSCT

      • Participants on Arm 1 must be fully engrafted post-HSCT.

    • Arm 2: CD19-targeted CAR T cell therapy (brexucabtagene autoleucel, tisagenlecleucel, obecabtagene autoleucel, investigational CD19 CAR T cell therapy)

      • Participants on Arm 2 must be fully recovered from cytopenia
  • PATIENTS AFTER DAY +30 FOLLOWING CELLULAR THERAPY: Day 30 (+/- 5 days) marrow post cellular therapy should show evidence of complete morphologic remission defined as < 5% bone marrow (BM) blasts, no extramedullary disease, and transfusion independence
  • PATIENTS AFTER DAY +30 FOLLOWING CELLULAR THERAPY: Participant should have no morphological evidence of relapse

  • PATIENTS AFTER DAY +30 FOLLOWING CELLULAR THERAPY: Absolute neutrophil count (ANC) ≥ 500/mm^3 for 3 days

    • NOTE: Patients are allowed growth factors
  • PATIENTS AFTER DAY +30 FOLLOWING CELLULAR THERAPY: Platelets ≥ 75,000/mm^3
  • PATIENTS AFTER DAY +30 FOLLOWING CELLULAR THERAPY: Hemoglobin ≥ 9g/dL
  • PATIENTS AFTER DAY +30 FOLLOWING CELLULAR THERAPY: Total bilirubin ≤ 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease)
  • PATIENTS AFTER DAY +30 FOLLOWING CELLULAR THERAPY: Aspartate aminotransferase (AST) ≤ 3.0 x ULN
  • PATIENTS AFTER DAY +30 FOLLOWING CELLULAR THERAPY: Alanine aminotransferase (ALT) ≤ 3.0 x ULN
  • PATIENTS AFTER DAY +30 FOLLOWING CELLULAR THERAPY: serum creatinine <1.5 mg/dL

  • PATIENTS AFTER DAY +30 FOLLOWING CELLULAR THERAPY: Left ventricular ejection fraction (LVEF) ≥ 50%

    • Note: To be performed within 28 days prior to day 1 of protocol therapy

  • PATIENTS AFTER DAY +30 FOLLOWING CELLULAR THERAPY: Bazett's corrected QT interval (QTcB) ≤ 480 ms

    • Note: To be performed within 28 days prior to day 1 of protocol therapy
  • PATIENTS AFTER DAY +30 FOLLOWING CELLULAR THERAPY: Oxygen (O2) saturation > 90% on room air

  • PATIENTS AFTER DAY +30 FOLLOWING CELLULAR THERAPY: Seronegative for HIV antigen (Ag)/antibody (Ab) combination (combo), hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative) OR

    • If seropositive for HIV, HCV or HBV, nucleic acid quantitation must be performed. Viral load must be undetectable. HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial

  • PATIENTS AFTER DAY +30 FOLLOWING CELLULAR THERAPY: Meets other institutional and federal requirements for infectious disease titer requirements

    • Note Infectious disease testing to be performed within 28 days prior to day 1 of protocol therapy
  • PATIENTS AFTER DAY +30 FOLLOWING CELLULAR THERAPY: Women of childbearing potential (WOCBP): Negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

  • PATIENTS AFTER DAY +30 FOLLOWING CELLULAR THERAPY: Agreement by females and males of childbearing potential* to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 120 days after the last dose of protocol therapy.

    • Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)

Exclusion Criteria:

  • Prior treatment failure with asciminib
  • Treatment with strong inducers of CYP3A is not allowed and should be switched to an alternative at least 1 week prior to the start of study treatment
  • ARM 1: Treatment with prior HSCT is allowed
  • ARM 2: Treatment with prior CAR T cell therapy is allowed

  • Cardiac or cardiac repolarization abnormality, including any of the following:

    • History within 6 months prior to starting study treatment of myocardial infarction (MI), or coronary artery bypass graft (CABG)
    • Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II and third-degree AV block)
    • Fridericia's corrected QT interval (QTcF) at screening ≥ 450 msec (male patients), ≥ 470 msec (female patients)
    • Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome
  • History of pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis
  • ARM 1: Active grade 3 or higher graft-versus-host disease (GVHD) after allogeneic HSCT within 14 days of enrollment. Note: prednisone administration (flat dose of 0.5 mg/kg) is allowed. Patients receiving any other medication to control active/progressive GVHD will be excluded
  • Clinically significant uncontrolled illness
  • Active infection not responding to treatment
  • Other active malignancy. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  • Females only: Pregnant or breastfeeding
  • Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
  • Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

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

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
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.
Experimental: Treatment (Asciminib)
Patients receive asciminib PO QD or BID on days 1-28 of each cycle. Cycles repeat every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography during screening and as clinically indicated, and bone marrow biopsy, bone marrow aspirate and blood sample collection throughout the study.
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Other: Survey Administration
Ancillary studies
Procedure: Bone Marrow Aspiration
Undergo bone marrow aspiration
Drug: Asciminib
Given PO
Other Names:
  • ABL001
  • ABL-001
  • ABL 001
Procedure: Bone Marrow Biopsy
Undergo bone marrow biopsy
Other Names:
  • Biopsy of Bone Marrow
  • Biopsy, Bone Marrow
Procedure: Echocardiography Test
Undergo echocardiography
Other Names:
  • Echocardiography
  • EC

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
Incidence of adverse events
Time Frame: From start of treatment on day 1 to the end of cycle 1 on day 28
Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. The toxicity/adverse event information recorded on each subject will include type, severity, duration, attribution/ association with the study agent by arm and cycle. Tables will be constructed to summarize the observed incidence, severity and type of toxicity, including infection. Point estimates and 90% confidence intervals will be provided.
From start of treatment on day 1 to the end of cycle 1 on day 28

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of patients who have completed at least 3 cycles of asciminib and have taken ≥ 70% planned doses in each cycle post cellular therapy
Time Frame: Up to completion of 3 cycles (cycle length= 28 days)
The protocol therapy will be deemed feasible if > 70% or higher of patients meet this feasibility criteria. Point estimates and 90% confidence intervals will be provided.
Up to completion of 3 cycles (cycle length= 28 days)
Duration of remission
Time Frame: Up to 1 year after completion of study treatment
Point estimates and 90% confidence intervals will be provided.
Up to 1 year after completion of study treatment
Relapse including minimal residual disease (MRD) relapsed
Time Frame: Up to 1 year after completion of study treatment
MRD relapse assed by polymerase chain reaction (PCR) and flow cytometry. MRD relapse is defined as detectable leukemic cells at > 0.01% in morphological remission bone marrow. However, due to rate of false positivity of PCR BCR::ABL1, confirmation is required by either positive MRD flow or/and clonoSEQ > 0.01%. Will be calculated using the competing risk method. Point estimates and 90% confidence intervals will be provided.
Up to 1 year after completion of study treatment
Relapse free survival
Time Frame: From start of protocol therapy to relapse, or death, up to 1 year after completion of study treatment
Kaplan-Meier curves will be used for survival endpoints. Point estimates and 90% confidence intervals will be provided.
From start of protocol therapy to relapse, or death, up to 1 year after completion of study treatment
Overall survival
Time Frame: From start of protocol therapy to death regardless of cause, up to 1 year after completion of study treatment
Kaplan-Meier curves will be used for survival endpoints. Point estimates and 90% confidence intervals will be provided.
From start of protocol therapy to death regardless of cause, up to 1 year after completion of study treatment
Non-relapse mortality
Time Frame: From start of protocol therapy to death without relapse/progression, up to 1 year after completion of study treatment
Will be calculated using the competing risk method. Point estimates and 90% confidence intervals will be provided.
From start of protocol therapy to death without relapse/progression, up to 1 year after completion of study treatment
Switching tyrosine kinase inhibitors (TKI)
Time Frame: Up to 1 year after completion of study treatment
Defined as changing treatment to a different TKI due to asciminib toxicity or intolerability per the treating physician judgment. Point estimates and 90% confidence intervals will be provided.
Up to 1 year after completion of study treatment
Asciminib discontinuation
Time Frame: Up to 1 year
Discontinuation is defined as not taking asciminib > 28 days due to treatment-related toxicity. Point estimates and 90% confidence intervals will be provided.
Up to 1 year
Asciminib interruption
Time Frame: Up to 1 year
Interruption is defined as not taking asciminib for > 7 days because of treatment-related toxicity. Point estimates and 90% confidence intervals will be provided.
Up to 1 year
Rate of acute graft versus host disease (aGVHD) of grades 2-4 (arm 1)
Time Frame: From hematopoietic stem cell transplantation (HSCT) to day 180 post HSCT
Documented/biopsy proven aGVHD is graded according to Mount Sinai Acute graft versus host disease (GVHD) International Consortium (MAGIC) grading. Point estimates and 90% confidence intervals will be provided.
From hematopoietic stem cell transplantation (HSCT) to day 180 post HSCT
Rate of aGVHD of grades 3-4 (Arm 1)
Time Frame: From HSCT to day 180 post HSCT
Documented/biopsy proven aGVHD is graded according to MAGIC Grading. Point estimates and 90% confidence intervals will be provided.
From HSCT to day 180 post HSCT
GVHD-free, relapse-free survival (Arm 1)
Time Frame: From start of protocol therapy to the first observation of developing grade 3-4 aGVHD, chronic (c) GVHD requiring systemic therapy, relapse/progression, or death, whichever comes first, up to 1 year after completion of study treatment
Kaplan-Meier curves will be used for survival endpoints. Point estimates and 90% confidence intervals will be provided.
From start of protocol therapy to the first observation of developing grade 3-4 aGVHD, chronic (c) GVHD requiring systemic therapy, relapse/progression, or death, whichever comes first, up to 1 year after completion of study treatment

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.
City of Hope Medical Center

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.
National Cancer Institute (NCI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Ibrahim Aldoss, City of Hope Comprehensive Cancer Center

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 (Estimated)

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.
May 1, 2026

Primary Completion (Estimated)

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.
June 13, 2028

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.
June 13, 2028

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).
June 18, 2025

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.
June 18, 2025

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.
June 27, 2025

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.
June 27, 2025

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.
June 18, 2025

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.
June 1, 2025

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.
  • 25023 (Other Identifier: City of Hope Medical center)
  • P30CA033572 (U.S. NIH Grant/Contract)
  • NCI-2025-04103 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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.

Clinical Trials on B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1

Clinical Trials on Biospecimen Collection

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings