Inclusion Criteria:

* Patients must give voluntary written consent before performance of any study related procedures not part of standard medical care
* Diagnosis of MDS or MDS/MPN according to 2016 WHO criteria12
* Primary therapy failure with either hypomethylating agents (decitabine or azacitidine) defined as:
* Progression (according to 2006 IWG criteria)13 after initiation of azacitidine or decitabine treatment; or
* Failure to achieve complete or partial response or hematological improvement (according to 2006 IWG)13 after at least 4-6 cycles (4-weeks cycle) of azacitidine or decitabine; or
* Relapse after initial complete or partial response or hematological improvement (according to 2006 IWG criteria)13 observed after at least 4 cycles of azacitidine or decitabine.
* Eastern Cooperative Oncology Group (ECOG) Performance Status \< 2
* Subjects must have normal organ and marrow function defined as:
* If total bilirubin \< 2x upper limit of normal (\* Calculated creatinine clearance value of \> 30ml/min AND a serum creatinine \< 1.5mg/dL
* LVEF \>/= 50%
* Female patients who:
* Are postmenopausal for at least 1 year before the screening visit, OR
* Are surgically sterile, OR
* Agree to practice true abstinence from heterosexual contact or agree to use effective contraception without interruption during the study therapy and 90 days after the last dose
* Male patients who:
* Are surgically sterile, OR
* Agree to practice true abstinence from heterosexual contact or agree to use effective contraception without interruption during the study therapy and 90 days after the last dose

Exclusion Criteria:

* Prior treatment with CPX-351, or known hypersensitivity to CPX-351 or its components.
* Prior treatment with intensive chemotherapy.
* Any serious medical condition, laboratory abnormality, or psychiatric illness that, in the view of the treating physician, would place the participant at an unacceptable risk if he or she were to participate in the study or would prevent that person from giving informed consent.
* Any active malignancy (unrelated, non-hematological malignancy) diagnosed within the past 6 months of starting the study drug (other than curatively treated carcinoma-in-situ of the cervix or non-melanoma skin cancer).
* Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Known history of HIV or active hepatitis B or C.
* Major surgery within 2 weeks prior to study enrollment.
* Pregnant or lactating females
* Male and female patients who are fertile who do not agree to use an effective barrier methods of birth control (i.e. abstinence or 2 forms of contraception) to avoid pregnancy while receiving study treatment.