Recruiting

Phase 3

DA-90 vs. DAC, FLAG-IDA vs. CLAG-MA 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

Sponsor:

Polish Adult Leukemia Group

Code:

NCT03257241

Conditions

Acute Myeloid Leukemia

Eligibility Criteria

Sex: All

Age: 18 - 60

Healthy Volunteers: Not accepted

Interventions

A arm (DA-90)

B arm (DAC)

A arm (CLAG-M)

B arm (FLAG-IDA)

Study Details

Brief 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.

Conditions

Acute Myeloid Leukemia

Study ID

NCT03257241

Start date

Jul 3, 2017

Status verified date

Sep, 2021

Completion date

Dec 31, 2022

Anticipated

Primary completion date

Apr 1, 2022

Anticipated

Eligibility Criteria

Sex: All

Age: 18 - 60

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

582 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: A arm (DA-90)

Induction I:

DNR 90 mg/m2 D 1-3 in 30-60 min i.v. infusion
Ara-C 100 mg/m2 D 1-7 in 24 h i.v. infusion

active comparator: B arm (DAC)

Induction I:

DNR 60 mg/m2 D 1-3 in 30-60 min i.v. infusion
cladribine 5 mg/m2 D 1-5 in 2 h i.v. infusion prior to Ara-C
Ara-C 200 mg/m2 D 1-7 in 22 h i.v. infusion.

active comparator: A arm (CLAG-M)

Cladribine 5mg/m2 in 2 h i.v. infusion on days (1-5) Ara-C 2 g/m2 in 4 h i.v. infusion, 2 h after cladribine infusion on days (1-5) Mitoxantrone 10 mg/m2 i.v. 1xd on days (1-3) G-CSF 30MU s.c. 1xd from day 0 to 5 of the treatment (6 doses).

active comparator: B arm (FLAG-IDA)

Fludarabine 30 mg/m2 in 30-min i.v. infusion on days (1-5) Ara-C 2 g/m2 in 4 h i.v. infusion, 2 h after fludarabine infusion on days (1-5). Idarubicin 8 mg/m2 i.v. 1xd on days (1-3) G-CSF 30MU s.c. 1xd from day 0 to 5 of the treatment (6 doses).

Interventions

A arm (DA-90)

After confirming the diagnosis, assuming the inclusion criteria and exclusion criteria are respected, the patients are randomized to one of two standard induction treatment protocols (A arm: DA-90 vs B arm: DAC). After completing induction I, an early bone marrow assessment is performed on day 14 from the beginning of the treatment (+ day 7 after finishing chemotherapy) using the cytological method and MRD is assessed by the immunophenotyping method. Therapeutic decision is taken on the basis of the cytological assessment. Patients, in whom the percentage of blasts in the bone marrow on day 14 is > 10%, receive early induction II from day 16. An Immunophenotype test is a complementary examination.

B arm (DAC)

A arm (CLAG-M)

Patients who do not achieve CR after two courses of induction therapy or patients with relapsed leukemia are eligible for emergency treatment ("salvage") according to the CLAG- M or FLAG-IDA protocol.

B arm (FLAG-IDA)

Primary outcome measure

Induction regimen efficacy (DA-90 vs DAC) - I induction [ Time Frame: On +7 day after chemotherpay ]
Induction regimen efficacy (DA-90 vs DAC) - II induction [ Time Frame: On +28 day after chemotherapy or after complete morphology regeneration (if it occurs before day +28) ]
Salvage regimen efficacy (CLAG-M vs FLAG-IDA) - I reinduction [ Time Frame: On +28 day after chemotherapy or after complete morphology regeneration (if it occurs before day +28) ]
Salvage regimen efficacy (CLAG-M vs FLAG-IDA) - II reinduction [ Time Frame: On +28 day after chemotherapy or after complete morphology regeneration (if it occurs before day +28) ]

Central Contacts and Locations

Central contacts

Agnieszka Wierzbowska, Prof.

+48426895191 agawierzbowska@wp.pl

Locations

Weill Cornell Medicine

Recruiting

New York, New York, United States, 10021

Principal Investigator:

Gail Roboz, Prof.

More Information

Sponsor

Polish Adult Leukemia Group

Last update posted

Oct 1, 2021

Last verified

Sep, 2021

Keywords

aml
acute myeloid leukemia
DAC
DA-90
FLAG-IDA
CLAG-M
Ara-C
HiDAC

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Polish Adult Leukemia Group on 2021-10-01.