Role of the Therapy Tailored to Risk Factors in Treating Adult Patients (≤60) With Acute Myeloid Leukemia

NCT02072811 | Unknown Phase 3 DMC

• 1 other identifier: PALG-AML2012
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Myeloid Leukemia

Keywords

AML

Outcome Measures

Primary Outcomes (1)

• Complete remission after induction

  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.

  28 days

Study Arms (5)

Induction, DAC

OTHER

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).

Drug: DAC

II early induction, CLAG

OTHER

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

Drug: CLAG

Consolidation, I HAM cycle

OTHER

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

Drug: Consolidation, I HAM cycle

II Consolidation HiDAraC

OTHER

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).

Drug: II Consolidation HiDAraC

Consolidation, III HiDAraC cycle

OTHER

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.

Drug: Consolidation, III HiDAraC cycle

Interventions

DAC DRUG

* DNR 60 mg/m2 0,5h infusion iv on 1-3 days * 2-CdA 5 mg/m2 2h. infusion iv on 1-5 days * Ara-C 200 mg/m2 12h infusion iv 2h after end of infusion with 2CdA on 1-7 days

Also known as: - Cladribine, - Cytosine arabinoside [Ara-C], - Daunorubicin

Induction, DAC

CLAG DRUG

* G-CSF 30MU sc, on 0-5 days * Mitoxantrone 10mg/m2 30 min infusion iv, on 1-3 days * Cladribine 5mg/m2 in 2h infusion iv, on 1-5 days * Ara-C 2000mg/m2 4h infusion iv, infusion start after 2h of Cladribine infusion end, on 1-5 day

Also known as: - Granulocyte-colony stimulating factor [G-CSF], - Cladribine, - Mitoxantrone, - Cytosine arabinoside [Ara C]

II early induction, CLAG

Consolidation, I HAM cycle DRUG

* Ara-C 3g/m2; 3h infusion iv every 12h on 1,2,3 days * Mitoxantrone 10mg/m2; 0,5h infusion iv on 3,4,5 days

Also known as: - Mitoxantrone, - Cytosine arabinoside [Ara-C]

Consolidation, I HAM cycle

II Consolidation HiDAraC DRUG

• Ara-C 3g/m2 every 12h; 3h infusion iv on 1,3,5 days (+ mobilization of CD34+)

Also known as: - Cytosine arabinoside [Ara-C], - Cladribine

II Consolidation HiDAraC

Consolidation, III HiDAraC cycle DRUG

* Ara-C 3g/m2 every 12h; 3h infusion iv on 1,3,5 days * 2-CdA 5 mg/m2 2h infusion iv on 1,3,5 days, 2h before Ara-C

Also known as: - Cytosine arabinoside [Ara-C], - 2-CdA [Cladribine, 2-Chlorodeoxyadenosine]

Consolidation, III HiDAraC cycle

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• dr hab. n. med. Agnieszka Wierzbowska: lead
• Polish Adult Leukemia Group: collaborator
• Copernicus Memorial Hospital: collaborator

Study Sites (1)

Copernicus Memorial Hospital

Lodz, 93-510, Poland

RECRUITING

Related Publications (1)

• Pluta A, Robak T, Brzozowski K, Stepka K, Wawrzyniak E, Krawczynska A, Czemerska M, Szmigielska-Kaplon A, Grzybowska-Izydorczyk O, Nowicki M, Stelmach P, Kuydowicz M, Gromek T, Hus M, Helbig G, Grosicki S, Bodzenta E, Razny M, Wojcik K, Bolkun L, Kloczko J, Knopinska-Posluszny W, Piekarska A, Hellman A, Sobas M, Wrobel T, Patkowska E, Lech-Maranda E, Warzocha K, Holowiecki J, Giebel S, Wierzbowska A. Early induction intensification with cladribine, cytarabine, and mitoxantrone (CLAM) in AML patients treated with the DAC induction regimen: a prospective, non-randomized, phase II study of the Polish Adult Leukemia Group (PALG). Leuk Lymphoma. 2020 Mar;61(3):588-603. doi: 10.1080/10428194.2019.1678151. Epub 2019 Oct 29.

  PMID: 31661339 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Cladribine; Cytarabine; Daunorubicin; Granulocyte Colony-Stimulating Factor; Mitoxantrone; 2'-chloro-2'-deoxyadenosine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Central Study Contacts

Agnieszka Wierzbowska, dr hab.n.med.

CONTACT

+48426895191; agawierzbowska@wp.pl

Agnieszka Pluta, dr n.med.

CONTACT

+48426895191; agnieszka.pluta@op.pl

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: PhD in Copernicus Memorial Hospital, Hematology Department

Study Record Dates

• First Submitted: February 24, 2014
• First Posted: February 27, 2014
• Study Start: February 1, 2014
• Primary Completion: February 1, 2018
• Study Completion: February 1, 2018
• Last Updated: February 27, 2014

Record last verified: 2014-02

Locations

PL (1)