Role of the Therapy Tailored to Risk Factors in Treating Adult Patients (≤60) With Acute Myeloid Leukemia (PALG-AML2012)

February 25, 2014 updated by: dr hab. n. med. Agnieszka Wierzbowska

Evaluation of the Efficacy of Induction-consolidation Treatment Using a Double Induction in Patients With AML <60 Years Old, Depending on the Percentage of Blasts in the 14 Day, Residual Disease and Leukemic Hematopoietic Cells

In view of the diversity of the biology of acute myeloid leukemia (AML) therapy in individual patients must be individualized. One of the tools for this is molecular-cytogenetic stratification. It divides patients into five categories (prognostic groups): Favorable, Intermediate-1, Intermediate-2, Adverse and Very adverse risk. After remission proceedings are tailored depending on prognostic determined groups.

Research of PALG group in the application in the second line regimen CLAG and CLAG-M proved high effectiveness of this treatment with low toxicity. Considering experience of PALG groups, it seems that the use of the schema CLAG early as the second induction therapy is a viable treatment option.

Study Overview

Status

Status

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

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

Patients with AML with one of 5 prognostic categories based on modified cytogenetic-molecular stratification (European Leukemia Net Prognostic System - ENL)

Favorable risk

t(8;21)(q22;q22); RUNX1-RUNX1T1 inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11 Mutated NPM1 without FLT3-ITD (NK) Mutated CEBPA (NK)

Intermediate I risk

Mutated NPM1 with FLT3-ITD (NK) Wild-type NPM1 and FLT3-ITD (NK) Wild-type NPM1 without FLT3-ITD (NK)

Intermediate II risk

t(9;11)(p22;q22); MLLT3-MLL cytogenic abnormalities other than favorable or adverse

Adverse risk

Inv(3)(q21q26.2) or t(3;3)(q21;q26.2); RPN-EVI1

Very adverse risk monosomal karyotype (MK): -5 or del(5q); -7; abnl(17p); complex karyotype

Goals:

  • Evaluation of the impact of therapy tailored to the risk factors on outcome of AML patients aged ≤ 60.
  • Evaluation of the possibility to improve the results of induction therapy through the use of early 2nd induction in patients with persistent leukemic infiltration of the bone marrow at the 14th day,
  • Evaluation of the impact of the minimal residual disease (MRD) presence assessed by Immunophenotyping method, on the results of treatment of AML patients aged ≤ 60,
  • Assessing the significance of monitoring the number of leukemic stem cells (LSC) in bone marrow and peripheral blood and their influence on clinical course and outcome of AML treatment,
  • Assessment of the LSC determination usefulness in MRD monitoring in patients with AML,
  • Evaluation of the prognostic significance of the expression of CXCR-4 on the surface of leukemic cells and their impact on the clinical course and outcome of AML - trying to select a group of patients who potentially would benefit from the use of chemosensitization with plerixafor,
  • Evaluation of autologous HSCT effectiveness in consolidation therapy in AML patients from 3 following cytogenetic-molecular risk groups: Favorable, Intermediate I, Intermediate II,
  • Comparison of the overall survive (OS) and leukemia-free survival after autologous and allogeneic HSCT in AML patients from Intermediate I and Intermediate II cytogenetic-molecular risk groups (biological randomization donor vs. donor).

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 (Anticipated)

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.
400

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 3

Contacts and Locations

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Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Poland
      • Lodz, Poland, 93-510
        • Recruiting
        • Copernicus Memorial Hospital
        • Principal Investigator:
          • Agnieszka Wierzbowska, Dr hab. n. med.

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

14 years to 56 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Adult acute myeloid leukemia
  • Age: ≥18 and ≤ 60
  • Clinical condition of the patient allows to carry out induction therapy: ECOG performance status: ≤ 2 and the Hematopoietic Cell Transplant-Co-morbidity Index (HCT-I): ≤3
  • Informed consent to participate in the study (ICF signed)
  • The second early induction start criteria is in addition to the listed above, the percentage of the blasts on the level >10% on 7th day.

Exclusion Criteria:

  • No informed consent for participation in the study, mental illness, which don't allow to obtain informed consent and conduct the treatment according to the protocol
  • Pregnancy
  • HIV infection
  • Active cancer
  • Active hepatitis virus infection

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: Non-Randomized
  • Interventional Model: Parallel 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.
Other: Induction, DAC

The first stage of treatment.

First DAC induction cycle is common to all patients (regardless of risk group). After completion of induction I occurs early assessment of bone marrow on the +14 day after the start of treatment (+7 day after completion of chemotherapy).
Drug: DAC
  • DNR 60 mg/m2 0,5h infusion iv on 1-3 days
  • 2-CdA 5 mg/m2 2h. infusion iv on 1-5 days
  • Ara-C 200 mg/m2 12h infusion iv 2h after end of infusion with 2CdA on 1-7 days
Other Names:
  • - Cladribine
  • - Cytosine arabinoside [Ara-C]
  • - Daunorubicin
Other: II early induction, CLAG

Patients with blasts in the bone marrow in D14> 10% receive early second induction (CLAG) which start form +16 day.

Patients with blasts in the bone marrow in D14 ≤ 10% do not receive early second induction and are qualified to assess the response times on +28 day or after full morphology recovery (if it occurs before the +28 day
Drug: CLAG
  • G-CSF 30MU sc, on 0-5 days
  • Mitoxantrone 10mg/m2 30 min infusion iv, on 1-3 days
  • Cladribine 5mg/m2 in 2h infusion iv, on 1-5 days
  • Ara-C 2000mg/m2 4h infusion iv, infusion start after 2h of Cladribine infusion end, on 1-5 day
Other Names:
  • - Cladribine
  • - Granulocyte-colony stimulating factor [G-CSF]
  • - Mitoxantrone
  • - Cytosine arabinoside [Ara C]
Other: Consolidation, I HAM cycle

I induction cycle starts after complete remission (CR).

- After I consolidation, patients from Intermediate I an Intermediate II group (ELN prognostic system):

If compatible donor is present - allogeneic HSCT qualification after I or II consolidation. If compatible donor for allogeneic HSCT is not present - attempt to CD34+ mobilization for autologous SCT after II consolidation

- After I consolidation, patients from Adverse risk group (ELN prognostic system):

If compatible donor is present - immediate qualification for allogeneic HSCT.

- Finding a donor should be initiated in all patients, at the latest after the end of I induction. In the first place, it should be checked whether the patient has a donor family, if not - searching start for an unrelated donor. For patients with no compatible donor for allogeneic HSCT - need to start searching for an alternative donor
Drug: Consolidation, I HAM cycle
  • Ara-C 3g/m2; 3h infusion iv every 12h on 1,2,3 days
  • Mitoxantrone 10mg/m2; 0,5h infusion iv on 3,4,5 days
Other Names:
  • - Cytosine arabinoside [Ara-C]
  • - Mitoxantrone
Other: II Consolidation HiDAraC

Patients from all 5 risk group receive second after first consolidation [Ara-C] Patient from Very adverse risk receive Ara-C + CLA (Cladribine). If it is needed - more intensive consolidation treatment with 2-Cda.

Patients form Very adverse risk receive Maintenance treatment:

Decitabine 20 mg/m2 60 min infusion iv (Intravenous injection) for 5 days every 6 weeks.

Patients from Favorable, - Intermediate I an Intermediate II risk groups: CD34+ mobilization (HSCT qualification).
Drug: II Consolidation HiDAraC
• Ara-C 3g/m2 every 12h; 3h infusion iv on 1,3,5 days (+ mobilization of CD34+)
Other Names:
  • - Cladribine
  • - Cytosine arabinoside [Ara-C]
Other: Consolidation, III HiDAraC cycle

Patients from Favorable, Intermediate I an Intermediate II risk groups receive III consolidation or autologous HSCT (depends on results of mobilization).

Patients from Adverse risk receive III Consolidation HiDAraC + Cladribina (CLA) If no CR: CLAG-M reinduction therapy and after CR - treatment according to protocol.
Drug: Consolidation, III HiDAraC cycle
  • Ara-C 3g/m2 every 12h; 3h infusion iv on 1,3,5 days
  • 2-CdA 5 mg/m2 2h infusion iv on 1,3,5 days, 2h before Ara-C
Other Names:
  • - Cytosine arabinoside [Ara-C]
  • - 2-CdA [Cladribine, 2-Chlorodeoxyadenosine]

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
Complete remission after induction
Time Frame: 28 days

Outcome measure after induction:

At +28 day after treatment or after full morphology recovery (if it occurs before the +28 day)

Complete remission, according to Cheson's CR criteria:

  • Lack of extramedullary infiltration,
  • Platelet count> 100 G / L,
  • Neutrophil count> 1.0 G / L,
  • Lack of blast cells in the blood,
  • Bone marrow blasts <5% in the cytomorphology.

After induction treatment, patients are qualified for one of the pro-remission treatment options, which is associated with cytogenetic-molecular risk groups, according to the modification of the molecular ELN / MDACC.

Therapeutic decisions are being made according to cytogenetic-molecular stratification: Favorable, Intermediate-1, Intermediate-2, Adverse and Very adverse risk.
28 days

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.
dr hab. n. med. Agnieszka Wierzbowska

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.
Copernicus Memorial Hospital
Polish Adult Leukemia Group

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

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Study Major Dates

Study Start

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.
February 1, 2014

Primary Completion (Anticipated)

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, 2018

Study Completion (Anticipated)

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.
February 1, 2018

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).
February 24, 2014

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 25, 2014

First Posted (Estimate)

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 27, 2014

Study Record Updates

Last Update Posted (Estimate)

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.
February 27, 2014

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.
February 25, 2014

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, 2014

More Information

Terms related to this study

Keywords

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.
  • PALG-AML2012

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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