Inclusion Criteria:
- Acute myeloid leukemia (AML) other than acute promyelocytic leukemia (APL),
myelodysplastic syndrome with excess blasts-2 (MDS-EB2), or another high-risk myeloid
neoplasm (>= 10% blasts in the blood or marrow), having completed at least one cycle
of chemotherapy intended to induce remission
- Subjects must have MRD, defined as the presence of original disease detected by
multi-parameter flow cytometry and cytogenetic/molecular assessment within 90 days of
chemotherapy intended to induce remission:
- Abnormal cells identified by multiparameter flow cytometry, present at a
frequency of between 0% and 5% of total nucleated cells, judged in the opinion of
the hematopathologist to represent continued presence of malignant cells
- Abnormal karyotype; present in any number of metaphase cells
- Abnormal fluorescence in-situ hybridization; judged in the opinion of the
hematopathologist to represent continued presence of malignant cells
- The presence of any leukemia associated mutation as detected by DNA sequencing,
except mutations in DNMT3A, TET2, or ASXL1. This includes (but is not limited to)
the following genes: CBL (CDS), CSF3R (exons 14, 15, 17), EZH2 (exons 15-20),
FBXW7 (CDS), FGFR1 (exons 4, 11-17, partial 18), FLT3 (p.D835H), GATA1 (exons
2-3), GATA2 (exons 3-5), HRAS (exon 1-2), IDH1(p.R132), IDH2 (exon 4), JAK2 (exon
12, 14, 16), KIT (8-18), KMT2A (CDS), KRAS (CDS), MAP2K1 (exons 2, 3, 6), MPL
(exon 10), MYD88 (exon 3-5), NOTCH1 (exons 20, 26, 27), NPM1 (exon 12), NRAS
(CDS), PDGFRA (exons 12-18), PHF6 (CDS), PTEN (CDS), RB1 (CDS), RUNX1 (exon 4-8),
SF3B1 (exon 14-16), SRSF2 (exon 1), STAG2 (CDS), STAT3 (exons 20-21), TP53 (CDS),
U2AF1 (exons 2, 6), WT1 (CDS), and ZRSR2 (CDS)
- Allowable prior therapy:
- For the purposes of this study intensive chemotherapy will include regimens
listed below. Additional regimens may be included at the discretion of the study
principal investigator (PI)
- Any regimen including cytarabine at a dose of 100 mg/m^2/day for at least 7
days and an anthracycline at any dose +/- gemtuzumab ozogamicin (GO)
- Any regimen including cytarabine at a dose of at least 100 mg/m^2/day for at
least 5 days and a purine analog at any dose (e.g. clofarabine, fludarabine,
cladribine) +/- GO
- Ability to understand and voluntarily sign a written informed consent document (ICF)
- Absence of a concomitant illness with a likely survival of < 1 year
- Medically fit, defined as a treatment related mortality score (TRM) of =< 13.1
calculated according to Walter et al, Journal of Clinical Oncology (JCO) 2011
- Additionally, subjects should be eligible in the opinion of their treating physician
for allogeneic transplantation
- Bilirubin =< 2.5 x institutional upper limit of normal, unless elevation is thought to
be due to Gilberts syndrome or hemolysis (within 14 days of study start [unless
otherwise noted] to be enrolled in the study)
- Left ventricular ejection fraction >= 40% assessed by multiple gated acquisition scan
(MUGA), echocardiography or other appropriate diagnostic modality within 12 months of
enrollment with no clinical evidence of decompensated congestive heart failure
- Creatinine clearance of >= 30 mL/min as measured by Cockcroft Gault equation (within
14 days of study start [unless otherwise noted] to be enrolled in the study)
- Consent of female patients with a negative serum or urine pregnancy test to use a
medically acceptable method of contraception throughout the entire study period and
for 6 months following the last dose of CPX-351
- Male patients must be willing to refrain from sperm donation for 6 months following
the last dose of CPX-351 and must use adequate contraception throughout the entire
study period and for 6 months following the last dose of CPX-351
- Patients enrolling in this trial should intend to complete the treatments described
and should be eligible in the opinion of the treating physician for allogeneic
transplantation
- Patients must have a caregiver capable of providing post-HCT care, who will be present
once conditioning therapy begins
- The informed consent document (ICF) must be signed and dated by the subject or by the
subject's legally authorized representative if the subject is unable to sign
Exclusion Criteria:
- Allogeneic myeloablative hematopoietic cell transplant within 6 months
- Autologous hematopoietic cell transplant within 6 months
- Known Hypersensitivity to CPX-351
- Patients may not have known hypersensitivity to CPX-351, daunorubicin,
cytarabine, or liposomal products
- Prior treatment with two or more cycles of CPX-351
- Treatment within the last 30 days of other investigational antineoplastic agents
- Evidence of organ dysfunction likely to preclude safe transplantation including the
following:
- Symptomatic coronary artery disease or uncontrolled arrhythmia within the prior 3
months and since most recent anthracycline exposure
- Myocardial impairment of any cause resulting in heart failure as determined by
New York (NY) Heart Association Criteria (class III or IV)
- Corrected diffusion capacity of the lung for carbon monoxide (DLCOc) < 40% or
forced expiratory volume in 1 second (FEV1) < 50%
- Need for supplemental oxygen
- Active systemic fungal, bacterial, viral or other infection, unless under treatment
with anti-microbials and/or controlled or stable (e.g. if specific, effective therapy
is not available/feasible or desired [e.g. chronic viral hepatitis, human
immunodeficiency virus (HIV)])
- Female patients who are pregnant, nursing, or lactating
- Patients with an inability to accept blood transfusions
- Inability to give informed consent, or unable to comply with the treatment protocol
including appropriate supportive care, follow-up and tests
- Any other condition that would cause a risk to patients if they participate in the
trial
