Clinical Trials /

CPX-351 or CLAG-M Regimen for the Treatment of Acute Myeloid Leukemia or Other High-Grade Myeloid Neoplasms in Medically Less-Fit Patients

NCT04195945

Description:

This phase II trial studies how well CPX-351 or the CLAG-M regimen (consisting of the drugs cladribine, cytarabine, G-CSF, and mitoxantrone) works in treating medically less-fit patients with acute myeloid leukemia or other high-grade myeloid neoplasms. Drugs used in chemotherapy, such as CPX-351, cladribine, cytarabine, G-CSF, and mitoxantrone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving CPX-351 or the CLAG-M regimen at doses typically used for medically-fit patients with acute myeloid leukemia may work better than reduced doses of CPX-351 in treating medically less-fit patients with acute myeloid leukemia or other high-grade myeloid neoplasms.

Related Conditions:
  • Acute Myeloid Leukemia
  • Myeloid Neoplasm
Recruiting Status:

Recruiting

Phase:

Phase 2

URL:

https://clinicaltrials.gov/show/NCT04195945

Trial Eligibility

Document

Title

  • Brief Title: CPX-351 or CLAG-M Regimen for the Treatment of Acute Myeloid Leukemia or Other High-Grade Myeloid Neoplasms in Medically Less-Fit Patients
  • Official Title: Randomized Phase 2 Trial of CPX-351 (Vyxeos) vs. CLAG-M (Cladribine, Cytarabine, G-CSF, and Mitoxantrone) in Medically Less-Fit Adults With Acute Myeloid Leukemia (AML) or Other High-Grade Myeloid Neoplasm

Clinical Trial IDs

  • ORG STUDY ID: RG1005577
  • SECONDARY ID: NCI-2019-07640
  • SECONDARY ID: P30CA015704
  • SECONDARY ID: 10330
  • NCT ID: NCT04195945

Conditions

  • Acute Myeloid Leukemia
  • Myeloid Neoplasm

Interventions

DrugSynonymsArms
Liposome-encapsulated Daunorubicin-CytarabineCPX-351, Cytarabine-Daunorubicin Liposome for Injection, Liposomal AraC-Daunorubicin CPX-351, Liposomal Cytarabine-Daunorubicin, Liposome-encapsulated Combination of Daunorubicin and Cytarabine, Vyxeos, Daunorubicin and Cytarabine (Liposomal)Arm I (CPX-351)
Cladribine105014, 105014-F, 2-Chloro-2-Deoxyadenosine, 2-Chlorodeoxyadenosine, CdA, Cladribina, Leustat, Leustatin, Leustatine, RWJ-26251Arm II (CLAG-M)
CytarabineARA-cell, Arabine, Arabinofuranosylcytosine, Aracytidine, Beta-Cytosine Arabinoside, Cytarabinum, Cytarbel, Cytosar, Cytosine Arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920Arm II (CLAG-M)
Recombinant Granulocyte Colony-Stimulating Factor143011-72-7, Recombinant Colony-Stimulating Factor 3, rhG-CSFArm II (CLAG-M)
MitoxantroneDihydroxyanthracenedione, MitozantroneArm II (CLAG-M)

Purpose

This phase II trial studies how well CPX-351 or the CLAG-M regimen (consisting of the drugs cladribine, cytarabine, G-CSF, and mitoxantrone) works in treating medically less-fit patients with acute myeloid leukemia or other high-grade myeloid neoplasms. Drugs used in chemotherapy, such as CPX-351, cladribine, cytarabine, G-CSF, and mitoxantrone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving CPX-351 or the CLAG-M regimen at doses typically used for medically-fit patients with acute myeloid leukemia may work better than reduced doses of CPX-351 in treating medically less-fit patients with acute myeloid leukemia or other high-grade myeloid neoplasms.

Detailed Description

      OUTLINE: Patients are randomized to 1 of 2 arms in a 1:1 fashion. ARM I = CPX-351; ARM II =
      CLAG-M.

      ARM I (INDUCTION): Patients receive CPX-351 intravenously (IV) over 90 minutes on days 1, 3,
      and 5 in the absence of disease progression or unacceptable toxicity. Patients who achieve a
      response other than an MRDneg CR receive a second course of CPX-351 intravenously IV over 90
      minutes on days 1, 3, and 5 in the absence of disease progression or unacceptable toxicity.

      ARM I (POST-REMISSION): Patients who achieve a CR or CR with incomplete hematologic recovery
      (CRi) receive a reduced dose of CPX-351 IV over 90 minutes on days 1, 3, and 5 for up to 4
      additional courses in the absence of disease progression or unacceptable toxicity.

      ARM II (INDUCTION): Patients receive cladribine IV over 2 hours on days 1-5, cytarabine IV
      over 2 hours on days 1-5, G-CSF subcutaneously (SC) on days 0-5, and mitoxantrone IV over 60
      minutes on days 1-3 in the absence of disease progression or unacceptable toxicity. Patients
      who achieve a response other than an MRDneg CR receive a second course of cladribine IV over
      2 hours on days 1-5, cytarabine IV over 2 hours on days 1-5, G-CSF SC on days 0-5, and
      mitoxantrone IV over 60 minutes on days 1-3 in the absence of disease progression or
      unacceptable toxicity.

      ARM II (POST-REMISSION): Patients who achieve a CR/CRi receive an intermediate dose of
      cytarabine IV over 2 hours on days 1-6 for up to 4 additional courses in the absence of
      disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up periodically for up to 5 years.

Trial Arms

NameTypeDescriptionInterventions
Arm I (CPX-351)ExperimentalINDUCTION: Patients receive CPX-351 IV over 90 minutes on days 1, 3, and 5 in the absence of disease progression or unacceptable toxicity. Patients who achieve a response other than an MRDneg CR receive a second course of CPX-351 intravenously IV over 90 minutes on days 1, 3, and 5 in the absence of disease progression or unacceptable toxicity. POST-REMISSION: Patients who achieve a CR/CRi receive a reduced dose of CPX-351 IV over 90 minutes on days 1, 3, and 5 for up to 4 additional courses in the absence of disease progression or unacceptable toxicity.
  • Liposome-encapsulated Daunorubicin-Cytarabine
Arm II (CLAG-M)ExperimentalINDUCTION: Patients receive cladribine IV over 2 hours on days 1-5, cytarabine IV over 2 hours on days 1-5, G-CSF SC on days 0-5, and mitoxantrone IV over 60 minutes on days 1-3 in the absence of disease progression or unacceptable toxicity. Patients who achieve a response other than an MRDneg CR receive a second course of cladribine IV over 2 hours on days 1-5, cytarabine IV over 2 hours on days 1-5, G-CSF SC on days 0-5, and mitoxantrone IV over 60 minutes on days 1-3 in the absence of disease progression or unacceptable toxicity. POST-REMISSION: Patients who achieve a CR/CRi receive an intermediate dose of cytarabine IV over 2 hours on days 1-6 for up to 4 additional courses in the absence of disease progression or unacceptable toxicity.
  • Cladribine
  • Cytarabine
  • Recombinant Granulocyte Colony-Stimulating Factor
  • Mitoxantrone

Eligibility Criteria

        Inclusion Criteria:

          -  Diagnosis of untreated "high-grade" myeloid neoplasm (>=10% blasts in blood or bone
             marrow) or AML other than acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) or
             variants according to the 2016 World Health Organization (WHO) classification. Outside
             diagnostic material is acceptable to establish diagnosis; submission of peripheral
             blood specimen for flow cytometry performed at the study institution should be
             considered. Diagnostic material must have been submitted for cytogenetic and/or
             molecular testing as clinically appropriate

          -  Treatment-related mortality (TRM) score >= 13.1 as calculated with simplified model

          -  The use of hydroxyurea before enrollment is permitted; hydroxyurea should be
             discontinued prior to start of study treatment. Patients with symptoms/signs of
             hyperleukocytosis or white blood cells (WBC) > 100,000/uL or with concern for other
             complications of high tumor burden or leukostasis (e.g. hypoxia, disseminated
             intravascular coagulation) can be treated with leukapheresis or may receive up to 2
             doses of cytarabine (up to 500 mg/m^2) any time prior to enrollment

          -  Patients may have received low-intensity treatment (e.g. azacitidine/decitabine,
             lenalidomide, growth factors) for antecedent low-grade myeloid neoplasm (i.e. < 10%
             blasts in blood and bone marrow)

          -  Bilirubin < 2.0 mg/mL unless elevation is thought to be due to hepatic infiltration by
             neoplastic cells, Gilbert's syndrome, or hemolysis (assessed within 14 days prior to
             study day 0)

          -  Left ventricular ejection fraction (LVEF) >= 45%, assessed within 12 months prior to
             registration, e.g. by multigated acquisition scan (MUGA) scan or echocardiography or
             another appropriate diagnostic modality

          -  Women of childbearing potential and men must agree to use adequate contraception
             beginning at the signing of the consent until at least 4 weeks after the last dose of
             study drug

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Myeloid blast crisis of chronic myeloid leukemia (CML), unless patient is not
             considered candidate for tyrosine kinase inhibitor treatment

          -  Concomitant illness associated with a likely survival of < 1 year

          -  Active systemic fungal, bacterial, viral, or other infection, unless disease is under
             treatment with anti-microbials and/or controlled or stable. Patients with fever
             thought to be likely secondary to leukemia are eligible

          -  Known hypersensitivity to any study drug used in this trial

          -  Pregnancy or active breast feeding

          -  Concurrent treatment with any other approved or investigational anti-leukemia agent.
             Treatment with a FLT3-inhibitor for FLT3-mutated AML is permissible
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:3-month overall survival (OS)
Time Frame:Up to 3 months from date of start of protocol therapy
Safety Issue:
Description:Will evaluate whether CPX-351 or cladribine, cytarabine, granulocyte colony-stimulating factor (G-CSF), and mitoxantrone (CLAG-M), at doses typically used for medically-fit adults with AML, improve 3-month overall survival in medically-unfit adults with AML compared to attenuated dose CPX-351 as used in our previous institutional trial (32 units/m2 per dose).

Secondary Outcome Measures

Measure:Complete remission (CR) rates
Time Frame:Up to 5 years post treatment
Safety Issue:
Description:Will compare CR rates between the study arms.
Measure:MRDneg CR rates
Time Frame:Up to 5 years post treatment
Safety Issue:
Description:Will compare MRDneg CR rates between the study arms.
Measure:Response duration
Time Frame:Up to 5 years post treatment
Safety Issue:
Description:Will compare response duration between the study arms.
Measure:Relapse-free survival
Time Frame:Up to 5 years post treatment
Safety Issue:
Description:Will compare RFS between the study arms.
Measure:Incidence of adverse events
Time Frame:Up to 5 years post treatment
Safety Issue:
Description:Will use the CTCAE (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events) version 5.0 for toxicity and adverse event reporting. Will describe the toxicity profile and infectious complications of each study treatment.
Measure:30-day mortality rate
Time Frame:At 30 days
Safety Issue:
Description:
Measure:60-day mortality
Time Frame:At 60 days
Safety Issue:
Description:
Measure:Quality of life (QOL): questionnaire
Time Frame:Up to 5 years post treatment
Safety Issue:
Description:QOL of patients will be assessed longitudinally using the European Organization for Research and Treatment of Cancer (EORTC) core QOL questionnaire (QLQ-C30) and the newly developed acute myeloid leukemia-specific QOL instrument.
Measure:Patient use of medical resources (e.g. transfusions)
Time Frame:Up to 5 years post treatment
Safety Issue:
Description:Electronic medical chart review to enumerate the number of platelet and red blood cell transfusions administered, the number of days spent on IV antimicrobial therapy, and the number of days spent in the ICU

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Fred Hutchinson Cancer Research Center

Trial Keywords

  • Myeloid and Monocytic Leukemia
  • Other Hematopoietic

Last Updated

March 17, 2021