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
Trial Snapshot
- Phase
- Phase 3
- Sponsor
- Enrollment
- 400
- Locations
- 1
- Primary Endpoint
- Complete remission after induction
Study Overview
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)
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 60 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
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).
Intervention: DAC (Drug)
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
Intervention: CLAG (Drug)
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
Intervention: Consolidation, I HAM cycle (Drug)
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).
Intervention: II Consolidation HiDAraC (Drug)
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.
Intervention: Consolidation, III HiDAraC cycle (Drug)
Outcomes
Primary Outcomes
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.
Secondary Outcomes
No secondary outcomes reported
Investigators
dr hab. n. med. Agnieszka Wierzbowska
PhD in Copernicus Memorial Hospital, Hematology Department
Polish Adult Leukemia Group