Acute Biphenotypic Leukemia, Acute Myeloid Leukemia, Myelodysplastic Syndrome, Untreated Adult Acute Myeloid Leukemia
Conditions
Brief summary
This randomized clinical trial studies liposomal cytarabine-daunorubicin CPX-351 in treating patients with untreated myelodysplastic syndrome or acute myeloid leukemia. Drugs used in chemotherapy, such as liposomal cytarabine-daunorubicin CPX-351, 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.
Detailed description
PRIMARY OBJECTIVES: I. Estimate whether the 32 units/m\^2 or the 64 units/m\^2 or both dose levels of CPX-351 (liposomal cytarabine-daunorubicin CPX-351) are likely to improve treatment-related mortality (TRM) rate while keeping the complete remission (CR) rate constant in patients with untreated high-risk myelodysplastic syndrome (MDS) or non-acute promyelocytic leukemia (APL) acute myeloid leukemia (AML) at high risk of TRM. SECONDARY OBJECTIVES: I. Describe the CR/CR with incomplete platelet count recovery (CRp) rate after up to 4 cycles of induction/re-induction therapy. II. Describe the event-free survival, disease-free survival, and overall survival of patients who achieve CR/CRp. III. Estimate the frequency and severity of regimen-associated toxicities. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: INDUCTION/RE-INDUCTION: Patients receive lower-dose liposomal cytarabine-daunorubicin CPX-351 intravenously (IV) over 90 minutes on days 1, 3, and 5. Treatment repeats every 40 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR or CRp continue on to consolidation. CONSOLIDATION: Patients receive lower-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1 and 3. Treatment repeats every 40 days for 4 courses in the absence of disease progression or unacceptable toxicity. ARM II: (closed to accrual effective 4/21/14) INDUCTION/RE-INDUCTION: Patients receive higher-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5. Treatment repeats every 40 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR or CRp continue on to consolidation. CONSOLIDATION: Patients receive higher-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1 and 3. Treatment repeats every 40 days for 4 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 1 month.
Interventions
OTHERLaboratory Biomarker Analysis
Correlative studies
Given IV
Sponsors
National Cancer Institute (NCI)
Fred Hutchinson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of untreated high-risk MDS (\>= 10% blasts) or AML other than acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) or variants according to the 2008 World Health Organization (WHO) classification; patients with biphenotypic AML 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 * Prior hydroxyurea for AML is permitted but should be discontinued prior to start of CPX-351 treatment * Azacitidine, decitabine, lenalidomide, and growth factors are permitted for low-risk MDS (\< 10% blasts); all treatments for MDS should be discontinued prior to start of CPX-351 treatment * Treatment-related mortality (TRM) score \>= 13.1 as calculated with simplified model * Bilirubin \< 2.0 mg/mL x upper limit of normal; this requirement reflects the excretion of CPX-351 by the liver * Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \< 4.0 x upper limit of normal; this requirement reflects the excretion of CPX-351 by the liver * Left ventricular ejection fraction (LVEF) \>= 40%, assessed within 28 days prior to registration, e.g. by multi gated acquisition (MUGA) scan or echocardiography, or other appropriate diagnostic modality * Patients with symptoms/signs of hyperleukocytosis or white blood cell (WBC) \> 100,000/uL can be treated with leukapheresis prior to enrollment * Provide signed written informed consent
Exclusion criteria
* Refractory/relapsing blast crisis of chronic myelogenous leukemia (CML) * Concomitant illness associated with a likely survival of \< 1 year * Active systemic fungal, bacterial, viral, or other infection, unless under treatment with anti-microbials and controlled/stable, as defined as being afebrile and hemodynamically stable for 24-48 hours
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-related Mortality Rate. (TRM) | Up to 1 month after completion of study treatment | Estimate whether the 32 units/m2 or the 64 units/m2 or both dose levels of CPX-351 are likely to improve treatment-related mortality (TRM) rate while keeping the CR rate constant in patients with untreated high-risk MDS or non-APL AML at high risk of TRM. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Remission Rate (CR+CRp) | Up to day 28 | Overall Remission Rate for the CR/CR with incomplete platelet count recovery (CRp) rate after up to 4 cycles of induction/re-induction therapy. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I (Lower-dose Liposomal Cytarabine-daunorubicin CPX-351) INDUCTION/RE-INDUCTION: Patients receive lower-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5. Treatment repeats every 40 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR or CRp continue on to consolidation.
CONSOLIDATION: Patients receive lower-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1 and 3. Treatment repeats every 40 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Laboratory Biomarker Analysis: Correlative studies
Liposomal Cytarabine-Daunorubicin CPX-351: Given IV | 38 |
| Arm II (Closed to Accrual Effective 4/21/14) INDUCTION/RE-INDUCTION: Patients receive higher-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5. Treatment repeats every 40 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR or CRp continue on to consolidation.
CONSOLIDATION: Patients receive higher-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1 and 3. Treatment repeats every 40 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Laboratory Biomarker Analysis: Correlative studies
Liposomal Cytarabine-Daunorubicin CPX-351: Given IV | 10 |
| Total | 48 |
Baseline characteristics
| Characteristic | Arm I (Lower-dose Liposomal Cytarabine-daunorubicin CPX-351) | Arm II (Closed to Accrual Effective 4/21/14) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 28 Participants | 8 Participants | 36 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 2 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 38 Participants | 10 Participants | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 35 Participants | 10 Participants | 45 Participants |
| Region of Enrollment United States | 38 Participants | 10 Participants | 48 Participants |
| Sex: Female, Male Female | 13 Participants | 3 Participants | 16 Participants |
| Sex: Female, Male Male | 25 Participants | 7 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 10 / 38 | 5 / 10 |
| other Total, other adverse events | 38 / 38 | 10 / 10 |
| serious Total, serious adverse events | 0 / 38 | 0 / 10 |
Outcome results
Primary
Treatment-related Mortality Rate. (TRM)
Estimate whether the 32 units/m2 or the 64 units/m2 or both dose levels of CPX-351 are likely to improve treatment-related mortality (TRM) rate while keeping the CR rate constant in patients with untreated high-risk MDS or non-APL AML at high risk of TRM.
Time frame: Up to 1 month after completion of study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (Lower-dose Liposomal Cytarabine-daunorubicin CPX-351) | Treatment-related Mortality Rate. (TRM) | 6 Participants |
| Arm II (Closed to Accrual Effective 4/21/14) | Treatment-related Mortality Rate. (TRM) | 2 Participants |
Secondary
Overall Remission Rate (CR+CRp)
Overall Remission Rate for the CR/CR with incomplete platelet count recovery (CRp) rate after up to 4 cycles of induction/re-induction therapy.
Time frame: Up to day 28
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (Lower-dose Liposomal Cytarabine-daunorubicin CPX-351) | Overall Remission Rate (CR+CRp) | 10 Participants |
| Arm II (Closed to Accrual Effective 4/21/14) | Overall Remission Rate (CR+CRp) | 1 Participants |