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

Acute Myeloid Leukemia Clinical Trial

— PALG-AML2012  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02072811
• Other study ID #: PALG-AML2012
• Status: Recruiting
• Phase: Phase 3
• First received: February 24, 2014
• Last updated: February 25, 2014
• Start date: February 2014
• Est. completion date: February 2018

Study information

• Verified date: February 2014
• Source: Polish Adult Leukemia Group
• Contact: Agnieszka Wierzbowska, dr hab.n.med.
• Phone: +48426895191
• Email: agawierzbowska[@]wp.pl
• Is FDA regulated: No
• Health authority: Poland: Ministry of HealthPoland: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: February 2018
• Est. primary completion date: February 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

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
• 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
• 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
• II Consolidation HiDAraC
• Ara-C 3g/m2 every 12h; 3h infusion iv on 1,3,5 days (+ mobilization of CD34+)
• 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

Locations

Country	Name	City	State
Poland	Copernicus Memorial Hospital	Lodz

Sponsors (3)

Lead Sponsor	Collaborator
dr hab. n. med. Agnieszka Wierzbowska	Copernicus Memorial Hospital, Polish Adult Leukemia Group, Gliwice, Poland

Country where clinical trial is conducted

Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete remission after induction	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	No