Clinical trial NCT02072811: Role of the Therapy Tailored to Risk Factors in Treating Adult Patients (≤60) With Acute Myeloid Leukemia
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Acute Myeloid Leukemia
Keywords: AML
Lead sponsor: Polish Adult Leukemia Group
Sponsor class: OTHER
Collaborators: name: Polish Adult Leukemia Group
name: Copernicus Memorial Hospital
First posted: 2014-02-27
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: Complete remission after induction
timeFrame: 28 days
Secondary outcomes:
Other outcomes:
Locations:
city: Lodz
country: Poland
facility: Copernicus Memorial Hospital
Study officials:
References:
citation: Pluta A, Robak T, Brzozowski K, Stepka K, Wawrzyniak E, Krawczynska A, Czemerska M, Szmigielska-Kaplon A, Grzybowska-Izydorczyk O, Nowicki M, Stelmach P, Kuydowicz M, Gromek T, Hus M, Helbig G, Grosicki S, Bodzenta E, Razny M, Wojcik K, Bolkun L, Kloczko J, Knopinska-Posluszny W, Piekarska A, Hellman A, Sobas M, Wrobel T, Patkowska E, Lech-Maranda E, Warzocha K, Holowiecki J, Giebel S, Wierzbowska A. Early induction intensification with cladribine, cytarabine, and mitoxantrone (CLAM) in AML patients treated with the DAC induction regimen: a prospective, non-randomized, phase II study of the Polish Adult Leukemia Group (PALG). Leuk Lymphoma. 2020 Mar;61(3):588-603. doi: 10.1080/10428194.2019.1678151. Epub 2019 Oct 29.