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.
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
- SECONDARY ID:
RG9217016
- NCT ID:
NCT03012672
Conditions
- Acute Leukemia of Ambiguous Lineage
- Acute Myeloid Leukemia
- Myeloid Neoplasm
Interventions
Drug | Synonyms | Arms |
---|
Cladribine | 2-CdA, 2CDA, CdA, Cladribina, Leustat, Leustatin, Leustatine, RWJ-26251 | Arm 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-28453 | Arm I (higher-dose) |
Granulocyte Colony-Stimulating Factor | Colony Stimulating Factor 3, Colony-Stimulating Factor (Granulocyte), Colony-Stimulating Factor 3, CSF3, G CSF, G-CSF, Granulocyte Colony Stimulating Factor, Pluripoietin | Arm I (higher-dose) |
Mitoxantrone Hydrochloride | CL 232315, DHAD, DHAQ, Dihydroxyanthracenedione Dihydrochloride, Mitoxantrone Dihydrochloride, Mitoxantroni Hydrochloridum, Mitozantrone Hydrochloride, Mitroxone, Neotalem, Novantrone, Onkotrone, Pralifan | Arm 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):
INDUCTION: 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.
CONSOLIDATION: Patients who achieve complete response (CR)/CR with incomplete count recovery
(CRi) with up to 2 courses of Induction receive G-CSF, cladribine, and cytarabine as in
Induction. Courses repeat every 6 weeks for up to 4 courses in the absence of disease
progression or unacceptable toxicity.
ARM II (LOWER-DOSE):
INDUCTION: 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.
CONSOLIDATION: Patients who achieve complete response (CR)/CR with incomplete count recovery
(CRi) with up to 6 courses of Induction receive G-CSF, cladribine, and cytarabine as in
Induction. Courses repeat 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
Name | Type | Description | Interventions |
---|
Arm I (higher-dose) | Experimental | INDUCTION: Patients 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.
CONSOLIDATION: Patients who achieve CR/CRi with up to 2 courses of Induction receive G-CSF, cladribine, and cytarabine as in Induction. Courses repeat every 6 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. | - Cladribine
- Cytarabine
- Granulocyte Colony-Stimulating Factor
- Mitoxantrone Hydrochloride
|
Arm II (lower-dose) | Experimental | INDUCTION: 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.
CONSOLIDATION: Patients who achieve CR/CRi with up to 6 courses of Induction receive G-CSF, cladribine, and cytarabine as in Induction. Courses repeat every 6 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. | - Cladribine
- Cytarabine
- Granulocyte Colony-Stimulating Factor
- 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
leukostasis, white blood cell (WBC) > 100,000/uL, or acute symptoms felt related to
their high-grade myeloid neoplasm can be treated with leukapheresis or may receive up
to 1 dose of cytarabine (up to 500 mg/m^2) anytime prior to study day 1
- 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: | At end of enrollment |
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 |
Time Frame: | Up to 12 months |
Safety Issue: | |
Description: | Will be determined by a patient preference survey. 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 University of Washington Medical Center (UWMC) and Seattle Cancer Care Alliance (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: | Will be evaluated. |
Measure: | Event-free survival |
Time Frame: | Up to 5 years |
Safety Issue: | |
Description: | Will be determined by peripheral blood count and bone marrow evaluation and categorized according to criteria recommended by International Working Groups. |
Measure: | Fitness for intensive chemotherapy as measured by a treatment-related mortality (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 University of Washington Medical Center (UWMC) and Seattle Cancer Care Alliance (SCCA). |
Measure: | Overall survival |
Time Frame: | Up to 5 years |
Safety Issue: | |
Description: | Will be assessed for all patients. Will be determined by peripheral blood count and bone marrow evaluation and categorized according to criteria recommended by International Working Groups. |
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: | Will be measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30. Exploratory, descriptive, and observational methods will be used. |
Measure: | Relapse-free survival |
Time Frame: | Up to 5 years |
Safety Issue: | |
Description: | Will be determined by peripheral blood count and bone marrow evaluation and categorized according to criteria recommended by International Working Groups. |
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. |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | University of Washington |
Last Updated
January 7, 2021