Clinical Trials /

Higher or Lower Dose Cladribine, Cytarabine, and Mitoxantrone in Treating Medically Less Fit Patients With Newly Diagnosed Acute Myeloid Leukemia or Myeloid Neoplasm

NCT03012672

Description:

This randomized pilot trial studies how well higher or lower dose cladribine, cytarabine, and mitoxantrone work in treating medically less fit patients with newly diagnosed acute myeloid leukemia or myeloid neoplasm. Drugs used in chemotherapy, such as cladribine, cytarabine, 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. It is not yet known whether giving cladribine, cytarabine, and mitoxantrone at higher or lower dose may work better in treating patients with newly diagnosed acute myeloid leukemia.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Higher or Lower Dose Cladribine, Cytarabine, and Mitoxantrone in Treating Medically Less Fit Patients With Newly Diagnosed Acute Myeloid Leukemia or Myeloid Neoplasm
  • Official Title: Impact of Treatment Intensity on Survival, Quality of Life, and Resource Utilization in Medically Less Fit Adults With Acute Myeloid Leukemia and Analogous Myeloid Neoplasms: A Randomized Pilot Study

Clinical Trial IDs

  • ORG STUDY ID: 9759
  • SECONDARY ID: NCI-2016-02051
  • SECONDARY ID: 9759
  • SECONDARY ID: P30CA015704
  • NCT ID: NCT03012672

Conditions

  • Acute Myeloid Leukemia
  • Myeloid Neoplasm

Interventions

DrugSynonymsArms
Cladribine2-CdA, 2CDA, CdA, Cladribina, Leustat, Leustatin, Leustatine, RWJ-26251Arm I (higher-dose)
Cytarabine.beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-Cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosar-U, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453Arm I (higher-dose)
Granulocyte Colony-Stimulating FactorColony Stimulating Factor 3, Colony-Stimulating Factor (Granulocyte), Colony-Stimulating Factor 3, CSF3, G CSF, G-CSF, Granulocyte Colony Stimulating Factor, PluripoietinArm I (higher-dose)
Mitoxantrone HydrochlorideCL 232315, DHAD, DHAQ, Dihydroxyanthracenedione Dihydrochloride, Mitoxantrone Dihydrochloride, Mitoxantroni Hydrochloridum, Mitozantrone Hydrochloride, Mitroxone, Neotalem, Novantrone, Onkotrone, PralifanArm I (higher-dose)

Purpose

This randomized pilot trial studies how well higher or lower dose cladribine, cytarabine, and mitoxantrone work in treating medically less fit patients with newly diagnosed acute myeloid leukemia or myeloid neoplasm. Drugs used in chemotherapy, such as cladribine, cytarabine, 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. It is not yet known whether giving cladribine, cytarabine, and mitoxantrone at higher or lower dose may work better in treating patients with newly diagnosed acute myeloid leukemia.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To evaluate the feasibility of randomizing medically less fit adults with newly diagnosed
      acute myeloid leukemia (AML) or analogous myeloid neoplasms to either intensive or
      non-intensive induction and post remission chemotherapy.

      SECONDARY OBJECTIVES:

      I. To evaluate the attitude of patients and physicians toward randomization and explore
      reasons for treatment preference.

      II. To evaluate whether the ability to assess fitness for intensive chemotherapy can be
      improved by an augmented treatment-related mortality (TRM) score that includes additional
      (co-morbidity) factors, and to compare the ability of physicians and the prediction
      algorithm(s) to assess the likelihood of early death.

      III. To compare, within the limits of a pilot study, response, duration of response, and
      survival between patients receiving intensive and those receiving non-intensive
      chemotherapy.

      IV. To describe the impact of treatment intensity on quality of life of patients undergoing
      chemotherapy for newly diagnosed AML.

      V. To describe the impact of treatment intensity on medical resource utilization and care
      cost of patients undergoing chemotherapy for newly diagnosed AML.

      OUTLINE: Patients agreeable to randomization are randomized to 1 of 2 treatment arms.
      Patients not agreeable to randomization receive treatment based on their preference.

      ARM I (HIGHER-DOSE): Patients receive granulocyte colony-stimulating factor (G-CSF)
      subcutaneously (SC) on days 0-5, higher dose cladribine intravenously (IV) over 2 hours on
      days 1-5, higher dose cytarabine IV over 2 hours on days 1-5, and higher dose mitoxantrone
      IV over 60 minutes on days 1-3. Treatment repeats every 6 weeks for up to 4 courses in the
      absence of disease progression or unacceptable toxicity.

      ARM II (LOWER-DOSE): Patients receive G-CSF SC on days 0-5, lower dose cladribine IV over 2
      hours on days 1-5, lower dose cytarabine IV over 1 hour on days 1-5, and lower dose
      mitoxantrone IV over 60 minutes on days 1-3. Treatment repeats every 6 weeks for up to 12
      courses in the absence of disease progression or unacceptable toxicity.

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

Trial Arms

NameTypeDescriptionInterventions
Arm I (higher-dose)ExperimentalPatients receive G-CSF SC on days 0-5, higher dose cladribine IV over 2 hours on days 1-5, higher dose cytarabine IV over 2 hours on days 1-5, and higher dose mitoxantrone IV over 60 minutes on days 1-3. Treatment repeats every 6 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
  • Cladribine
  • Cytarabine
  • Mitoxantrone Hydrochloride
Arm II (lower-dose)ExperimentalPatients receive G-CSF SC on days 0-5, lower dose cladribine IV over 2 hours on days 1-5, lower dose cytarabine IV over 1 hour on days 1-5, and lower dose mitoxantrone IV over 60 minutes on days 1-3. Treatment repeats every 6 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
  • Cladribine
  • Cytarabine
  • Mitoxantrone Hydrochloride

Eligibility Criteria

        Inclusion Criteria:

          -  Diagnosis of untreated "high-grade" myeloid neoplasm (>= 10% myeloid blasts by
             morphology in bone marrow and/or peripheral blood) 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; patients with acute leukemias of
             ambiguous lineage are eligible; outside diagnostic material is acceptable as long as
             peripheral blood and/or bone marrow slides are reviewed at the study institution and
             cytogenetic/molecular information is available

          -  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 cell count (WBC) >100,000/uL can be treated with
             leukapheresis or may receive up to 1 dose of cytarabine (up to 500 mg/m^2) anytime
             prior to enrollment

          -  Patients may have received treatment (e.g. azacitidine/decitabine, lenalidomide,
             growth factors) for antecedent low-grade myeloid neoplasm

          -  Left ventricular ejection fraction (LVEF) >= 45%, assessed within 3 months prior to
             registration, e.g. by multigated acquisition (MUGA) scan or echocardiography, or
             other 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

          -  Known hypersensitivity to any study drug used in this trial

          -  Pregnancy or lactation

          -  Concurrent treatment with any other anti-leukemia agent
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Feasibility defined as proportion of patients willing to be randomized to either intensive or non-intensive induction and post remission chemotherapy
Time Frame:Up to 5 years
Safety Issue:
Description:Randomizing patients to either intensive or non-intensive induction and post remission chemotherapy will be considered feasible if the true proportion of patients willing to be randomized is 60% or higher.

Secondary Outcome Measures

Measure:Attitude of patients toward randomization as determined by a patient preference survey
Time Frame:Up to 12 months
Safety Issue:
Description:Exploratory, descriptive, and observational methods will be used.
Measure:Care costs
Time Frame:Up to 5 years
Safety Issue:
Description:The costs associated with inpatient and outpatient management will be calculated using electronic billing information from the UWMC and SCCA. Costs will be converted from charges using departmental cost-to-charge ratios. Descriptive information identifying major cost drivers and total/subset costs per phase of treatment will be reported.
Measure:Duration of response
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:Fitness for intensive chemotherapy as measured by a TRM score that includes additional co-morbidity factors
Time Frame:Up to 12 months
Safety Issue:
Description:The ability of physicians and the prediction algorithm(s) to assess the likelihood of early death will be compared.
Measure:Medical complications
Time Frame:Up to 5 years
Safety Issue:
Description:Information on medical complications (e.g. need for intensive care unit (ICU) level care, length of ICU stay, neutropenic fever, documented infections, bleeding, reasons for hospitalization) will be collected from the medical records from the University of Washington Medical Center (UWMC) and Seattle Cancer Care Alliance (SCCA).
Measure:Medical resource utilization
Time Frame:Up to 5 years
Safety Issue:
Description:Information on use of medical resources (e.g. platelet transfusions; days of IV antimicrobial therapy, total hospital length of stay) will be collected from the medical records from the UWMC and SCCA.
Measure:Quality of life as measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30
Time Frame:Up to 12 months
Safety Issue:
Description:Exploratory, descriptive, and observational methods will be used.
Measure:Response
Time Frame:Up to 5 years
Safety Issue:
Description:The differences in anti-leukemic efficacy between patients treated with lower-intensity chemotherapy and those treated with higher-intensity chemotherapy will be estimated. Exploratory, descriptive, and observational methods will be used.
Measure:Overall survival
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:Relapse-free survival
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:Event-free survival
Time Frame:Up to 5 years
Safety Issue:
Description:

Details

Phase:N/A
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Fred Hutchinson Cancer Research Center

Last Updated

February 10, 2017