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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 (PALG-AML1/2016)

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ClinicalTrials.gov Identifier: NCT03257241
Recruitment Status : Recruiting
First Posted : August 22, 2017
Last Update Posted : August 23, 2017
Sponsor:
Information provided by (Responsible Party):
Agnieszka Wierzbowska, Polish Adult Leukemia Group

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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: A arm (DA-90) Drug: B arm (DAC) Drug: A arm (CLAG-M) Drug: B arm (FLAG-IDA) Phase 3

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 582 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : July 3, 2017
Estimated Primary Completion Date : April 1, 2018
Estimated Study Completion Date : December 31, 2020


Arm Intervention/treatment
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
Drug: 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.
Other Name: Daunorubicin, Cytarabine

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.
Drug: B arm (DAC)
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.
Other Name: Daunorubicin, Cladribine, Cytarabine

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).
Drug: 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.
Other Name: Cladribine, Cytarabine, Mitoxantrone, G-CSF

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).
Drug: B arm (FLAG-IDA)
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.
Other Name: Fludarabine, Cytarabine, Idarubicin, G-CSF




Primary Outcome Measures :
  1. Induction regimen efficacy (DA-90 vs DAC) - I induction [ Time Frame: On +7 day after chemotherpay ]
    Comparison of total remission rates after 1 induction course of DA-90 and DAC.

  2. 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) ]
    Comparison of total remission rates after II induction course of DA-90 and DAC.

  3. 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) ]
    Comparison of total remission rates after I reinduction course of CLAG-M and FLAG-IDA

  4. 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) ]
    Comparison of total remission rates after II reinduction course of CLAG-M and FLAG-IDA



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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03257241


Contacts
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Contact: Agnieszka Wierzbowska, Prof. +48426895191 agawierzbowska@wp.pl

Locations
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Poland
Medical University of Bialystok Clinical Hospital Recruiting
Białystok, Poland, 15-276
Contact: Jarosław Piszcz, Dr         
Markiewicz Memorial Oncology Center Brzozow Recruiting
Brzozów, Poland, 36-200
Contact: Andrzej Pluta, Dr         
University Clinical Centre in Gdansk Recruiting
Gdańsk, Poland, 80-210
Contact: Maria Bieniaszewska, Dr         
Holycross Cancer Center Recruiting
Kielce, Poland, 25-001
Contact: Marzena Wątek, Dr         
Ludwik Rydygier Memorial Specialized Hospital Recruiting
Kraków, Poland, 30-001
Contact: Małgorzata Raźny, Dr         
Regional Specialised Hospital in Legnica Recruiting
Legnica, Poland, 59-220
Contact: Jadwiga Hołojda         
Independent Public University Hospital No. 1 in Lublin Recruiting
Lublin, Poland, 20-001
Contact: Marek Hus, Prof.         
Clinical Hospital at the Karol Marcinkowski Medical University in Poznan Recruiting
Poznań, Poland, 60-355
Contact: MAciej Kaźmierczak, Dr         
Copernicus Memorial Hospital in Lodz Comprehensive Cancer Center and Traumatology Recruiting
Łódź, Poland, 93-513
Contact: Agnieszka Wierzbowska, Prof.    +48426895191    agawierzbowska@wp.pl   
Sponsors and Collaborators
Polish Adult Leukemia Group
Investigators
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Principal Investigator: Sebastian Giebel, Prof. PALG

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Responsible Party: Agnieszka Wierzbowska, Study Coordinator, Polish Adult Leukemia Group
ClinicalTrials.gov Identifier: NCT03257241     History of Changes
Other Study ID Numbers: PALG-AML1/2016
First Posted: August 22, 2017    Key Record Dates
Last Update Posted: August 23, 2017
Last Verified: August 2017

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Agnieszka Wierzbowska, Polish Adult Leukemia Group:
aml
acute myeloid leukemia
DAC
DA-90
FLAG-IDA
CLAG-M
Ara-C
HiDAC

Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia
Neoplasms by Histologic Type
Neoplasms
Fludarabine
Fludarabine phosphate
Cytarabine
Daunorubicin
Mitoxantrone
Idarubicin
Cladribine
Lenograstim
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antiviral Agents
Anti-Infective Agents
Adjuvants, Immunologic
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Analgesics
Sensory System Agents
Peripheral Nervous System Agents