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

NCT03257241 | Unknown Phase 3 DMC

• 1 other identifier: PALG-AML1/2016
• Study Type: interventional
• Target: 582
• Locations: 2 countries
• Sites: 10

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

Keywords

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

Outcome Measures

Primary Outcomes (4)

• Induction regimen efficacy (DA-90 vs DAC) - I induction

  Comparison of total remission rates after 1 induction course of DA-90 and DAC.

  On +7 day after chemotherpay

• Induction regimen efficacy (DA-90 vs DAC) - II induction

  Comparison of total remission rates after II induction course of DA-90 and DAC.

  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

  Comparison of total remission rates after I reinduction course of CLAG-M and FLAG-IDA

  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

  Comparison of total remission rates after II reinduction course of CLAG-M and FLAG-IDA

  On +28 day after chemotherapy or after complete morphology regeneration (if it occurs before day +28)

Study Arms (4)

A arm (DA-90)

ACTIVE COMPARATOR

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

Drug: A arm (DA-90)

B arm (DAC)

ACTIVE COMPARATOR

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.

Drug: B arm (DAC)

A arm (CLAG-M)

ACTIVE COMPARATOR

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).

Drug: A arm (CLAG-M)

B arm (FLAG-IDA)

ACTIVE COMPARATOR

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).

Drug: B arm (FLAG-IDA)

Interventions

A arm (DA-90) DRUG

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.

Also known as: Daunorubicin, Cytarabine

A arm (DA-90)

B arm (DAC) DRUG

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.

Also known as: Daunorubicin, Cladribine, Cytarabine

B arm (DAC)

A arm (CLAG-M) DRUG

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.

Also known as: Cladribine, Cytarabine, Mitoxantrone, G-CSF

A arm (CLAG-M)

B arm (FLAG-IDA) DRUG

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.

Also known as: Fludarabine, Cytarabine, Idarubicin, G-CSF

B arm (FLAG-IDA)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnosis of acute myeloid leukemia (≥20% of blasts in the bone marrow)
• 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.
• Age ≥ 18 years and ≤60 years while signing a written consent form
• 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)
• 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
• A negative pregnancy test result in women of reproductive age, or women after menopause

You may not qualify if:

• Diagnosis or suspicion of acute promyelocytic leukemia (APL)
• Lack of consent for participation in the study
• Active cancerous disease other than AML (with the exception of carcinoma basocellulare cutis)
• 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
• Pregnancy
• Uncontrolled mycotic, bacterial or viral systemic infection
• Active HIV, or hepatitis B or C virus infection
• The use of another form of experimental therapy within 28 days of the commencement of treatment
• The presence of another comorbidity or improper study results which could expose the patient to excessive hazard (HCT-CI\>3)
• Any other serious health disorders, abnormal results of laboratory tests or mental disorders which would interfere with participation in the study
• The presence of other comorbidities which would disturb the interpretation of the data obtained in the study.

Sponsors & Collaborators

• Polish Adult Leukemia Group: lead

Study Sites (10)

Weill Cornell Medicine

New York, New York, 10021, United States

RECRUITING

Medical University of Bialystok Clinical Hospital

Bialystok, 15-276, Poland

RECRUITING

Markiewicz Memorial Oncology Center Brzozow

Brzozów, 36-200, Poland

RECRUITING

University Clinical Centre in Gdansk

Gdansk, 80-210, Poland

RECRUITING

Holycross Cancer Center

Kielce, 25-001, Poland

RECRUITING

Ludwik Rydygier Memorial Specialized Hospital

Krakow, 30-001, Poland

RECRUITING

Regional Specialised Hospital in Legnica

Legnica, 59-220, Poland

RECRUITING

Copernicus Memorial Hospital in Lodz Comprehensive Cancer Center and Traumatology

Lodz, 93-513, Poland

RECRUITING

Independent Public University Hospital No. 1 in Lublin

Lublin, 20-001, Poland

RECRUITING

Clinical Hospital at the Karol Marcinkowski Medical University in Poznan

Poznan, 60-355, Poland

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Daunorubicin; Cytarabine; Decitabine; Cladribine; Mitoxantrone; Granulocyte Colony-Stimulating Factor; fludarabine; Idarubicin

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Azacitidine; Aza Compounds; Ribonucleosides; 2-Chloroadenosine; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyadenosines; Deoxyribonucleosides; Anthraquinones; Anthrones; Anthracenes; Quinones; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Sebastian Giebel, Prof.

  Polish Adult Leukemia Group

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Agnieszka Wierzbowska, Prof.

CONTACT

+48426895191; agawierzbowska@wp.pl

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Study Coordinator

Model Details: Comparison of the efficacy of two standard induction treatment protocols (DA-90 and DAC) in patients with newly-diagnosed AML (with the exception of acute promyelocytic leukemia). Comparison of the efficacy of two standard reinduction treatment protocols (CLAG-M and FLAG-IDA) in patients with refractory and relapsed AML.

Study Record Dates

• First Submitted: August 4, 2017
• First Posted: August 22, 2017
• Study Start: July 3, 2017
• Primary Completion: April 1, 2022
• Study Completion: December 31, 2022
• Last Updated: October 1, 2021

Record last verified: 2021-09

Locations

US (1); PL (9)