This phase I trial studies best dose and side effects of liposome-encapsulated daunorubicin-cytarabine (CPX-351) and how well it works in treating patients with high risk myelodysplastic syndrome or chronic myelomonocytic leukemia that has come back or has not responded to treatment. Drugs used in chemotherapy, such as liposome-encapsulated daunorubicin-cytarabine, 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.
PRIMARY OBJECTIVES: I. To characterize the safety and tolerability of CPX-351 in patients with intermediate-2 or high-risk myelodysplastic syndrome (MDS). (Dose Escalation Stage) II. To determine the maximum tolerated dose (MTD) of intravenous CPX-351 in patients with intermediate-2 or high-risk MDS. (Dose Escalation Stage) III. To further characterize the safety and tolerability of CPX-351 in patients with intermediate-2 and high-risk MDS. (Dose-Expansion Stage) IV. To evaluate preliminary efficacy of CPX-351 in patients with intermediate-2 or high-risk MDS. (Dose-Expansion Stage) SECONDARY OBJECTIVES: I. To assess overall response (OR) rate. II. To assess overall survival. III. To assess duration of response. IV. To assess relapse-free survival. V. To assess safety profile. OUTLINE: This is a dose-escalation study. INDUCTION THERAPY: Patients receive liposome-encapsulated daunorubicin-cytarabine intravenously (IV) over 90 minutes on days 1, 3, and 5 in the absence of disease progression or unacceptable toxicity. After 2-5 weeks, patients who do not achieve a complete response (CR)/CR with incomplete bone marrow recovery (CRi)/CR with incomplete platelet recovery (CRp), have acceptable or no toxicity, and have stable disease and no disease progression may receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3 in the absence of disease progression or unacceptable toxicity. CONSOLIDATION THERAPY: Patients who achieve at least a hematological improvement (HI) response, receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. After 5-8 weeks, patients who do not show clinically significant disease progression or unacceptable toxicity may receive liposome-encapsulated daunorubicin-cytarabine for up to 12 additional cycles. After completion of study treatment, patients are followed up at 30 days and then every 6 months thereafter.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
38
Given IV
M D Anderson Cancer Center
Houston, Texas, United States
RECRUITINGIncidence of adverse events (dose-escalation stage)
Safety data of the patients will be summarized using descriptive statistics such as mean, standard deviation, median, and range. Toxicity type, severity, and attribution will be summarized for each patient using frequency tables.
Time frame: Up to 30 days
Maximum-tolerated dose (MTD) of liposome-encapsulated daunorubicin-cytarabine (dose-escalation stage)
Defined as the highest dose level in which a dose-limiting toxicity (DLT) occurs within at most 1 out of 6 patients treated. DLTs are defined as any related non-hematological Common Terminology Criteria for Adverse Events grade \>= 3 adverse events that prevent further administration of the agent at that same dose level.
Time frame: Up to 28 days
Incidence of adverse events (dose-expansion stage)
Safety data of the patients will be summarized using descriptive statistics such as mean, standard deviation, median, and range. Toxicity type, severity, and attribution will be summarized for each patient using frequency tables.
Time frame: Up to 30 days
Objective response rate (ORR) (dose-expansion stage)
Defined as complete response (CR), partial response, CR with incomplete bone marrow recovery, marrow CR or hematological improvement. Will be estimated along with 95% confidence intervals treated at the MTD (i.e., including those treated at the MTD during dose escalation and dose expansion phases). The association between ORR and patient's clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test, as appropriate.
Time frame: Up to 1.5 years
Overall response rate
Time frame: Up to 1.5 years
Overall survival
The distribution of time-to-event endpoints will be estimated using the method of Kaplan and Meier. Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests.
Time frame: Up to 1.5 years
Duration of response
Will be summarized using descriptive statistics such as mean, standard deviation, median and range.
Time frame: Up to 1.5 years
Relapse-free survival
The distribution of time-to-event endpoints will be estimated using the method of Kaplan and Meier. Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests.
Time frame: Up to 1.5 years
Incidence of adverse events
Safety data of the patients will be summarized using descriptive statistics such as mean, standard deviation, median, and range. Toxicity type, severity, and attribution will be summarized for each patient using frequency tables.
Time frame: Up to 1.5 years
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