A PALG Prospective Multicenter Clinical Trial to Compare the Efficacy of Two Standard Induction Therapies (DA-90 vs DAC) and Two Standard Salvage Regimens (FLAG-IDA vs CLAG-M) in AML Patients ≤ 60 Years Old

• Status: Recruiting
• Trial end date: 2022-12-31
• Target enrollment: 0
• Participant gender: All

Summary

The study will include newly-diagnosed AML patients, not suffering acute promyelocytic leukemia; aged 18-60 years, who are eligible for standard induction chemotherapy. The patients will be randomized to one standard induction regimen (DAC or DA-90). At day seven after completion of induction, a bone marrow aspiration with MRD will be performed for an early evaluation of response to treatment. Patients without bone marrow blast reduction below 10% at day seven after induction will be given a second early induction course. Patients who do not achieve CR after two induction courses will be randomized to one of the standard salvage regimens (FLAG-IDA or CLAG-M). Postremission treatment intensity will be adjusted to risk group based on cytogenetic and molecular risk factors at diagnosis and AML biology (secondary AML, therapy related AML). Patients with a low risk of relapse will be allocated to consolidation, with three courses of high doses of Ara-C (HiDAC), or two courses of HiDAC with subsequent autologous stem cell transplantation. Intermediate- or high-risk patients will be referred for allogeneic stem cell transplantation, if they have a matched donor. Until transplantation, consolidation with HiDAC will be continued.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Polish Adult Leukemia Group
• Treatments: Cladribine; Cytarabine; Daunorubicin; Fludarabine; Fludarabine phosphate; Idarubicin; Lenograstim; Mitoxantrone

Criteria

Inclusion Criteria:

1. Diagnosis of acute myeloid leukemia (≥20% of blasts in the bone marrow)

2. Previously untreated AML

• AML de novo

• AML secondary to the myelodysplastic syndromes (MDS)

• AML secondary towards used therapies or agents, which can induce leukemia (e.g., irradiation, alkylating drugs, topoisomerase II inhibitors) with a primary tumor in remission for at least 2 years.

3. Age ≥ 18 years and ≤60 years while signing a written consent form

4. A clinical condition allowing induction treatment to be performed

• General state according to the ECOG ≤ 2 scale (Annex 1)

• Index of comorbidities, HCT-CI ≤ 3, according to Sorror et al. (43) (Annex 2)

5. Normal function of the liver and kidneys defined as:

• Bilirubin of ≤1.5 of the upper limit of the normal range

• ALT ≤2.5 x of the upper limit of the normal range

• AST ≤2.5 x of the upper limit of the normal range

• Creatinine ≤1.5 of the upper limit of the normal range

6. A negative pregnancy test result in women of reproductive age, or women after menopause

7. The patient has understood and signed an informed consent form (Annex 3)

8. The patient has given consent to adhere to scheduled appointments in the study and the remaining protocol requirements.

Exclusion Criteria:

1. Diagnosis or suspicion of acute promyelocytic leukemia (APL)

2. Lack of consent for participation in the study

3. Active cancerous disease other than AML (with the exception of carcinoma basocellulare cutis)

4. Diagnosis of unstable angina pectoris, significant cardiac arrhythmia or class III or IV congestive heart failure according to the New York Heart Association (NYHA) functional classification

5. Pregnancy

6. Uncontrolled mycotic, bacterial or viral systemic infection

7. Active HIV, or hepatitis B or C virus infection

8. The use of another form of experimental therapy within 28 days of the commencement of treatment

9. The presence of another comorbidity or improper study results which could expose the patient to excessive hazard (HCT-CI>3)

10. Any other serious health disorders, abnormal results of laboratory tests or mental disorders which would interfere with participation in the study

11. The presence of other comorbidities which would disturb the interpretation of the data obtained in the study.