CPX-351 as a Novel Approach for the Treatment of Older Patients With AML and MDS

The purpose of this study is to evaluate how effective lower doses of CPX-351 are in older participants with relapsed/refractory acute myeloid leukemia (AML) who are not eligible to receive intensive chemotherapy and in participants with myelodysplastic syndromes (MDS) after Hypomethylating Agents (HMA) failure.

Currently, elderly patients with AML and high risk MDS, who are ineligible to receive induction chemotherapy and fail HMA +/- combination, have very poor outcomes and there is no FDA-approved therapy outside of some targeted therapies which can only be applied to a small patient population. CPX-351 is an investigational (experimental) drug that works by combining two anti-cancer drugs cytarabine and daunorubicin. CPX-351 is experimental because it is only FDA approved for the treatment of adults with two types of AML: newly diagnosed therapy-related AML or AML with myelodysplasia-related changes.

This is an open label clinical trial of lower doses of CPX-351 in relapsed/primary refractory older AML and MDS patients ineligible to receive intensive chemotherapy. The first arm is for particpants with primary refractory/relapsed AML and the second arm is for higher risk MDS participants after HMA failure.

Eligibility Criteria:
Inclusion Criteria:

* Primary refractory or relapsed AML (defined by 2016 World Health Organization \[WHO\] criteria) patients who are not suitable for or not willing to receive intensive chemotherapy as evaluated by the treating physician. Primary refractory disease is defined as:

  * Failure to achieve a CR, CRi, or mLFS (defined as \<5% Bone Marrow (BM) blasts) after receiving 1 or 2 cycles of remission induction chemotherapy.
  * Failure to achieve a CR, CRi, or MLFS (defined as \<5% BM blasts) after receiving 4 cycles of non-intensive chemotherapy or whose disease progressed at any time point during the treatment.
* Participants with MDS (according to 2016 WHO criteria) who did not respond to treatment with azacitidine, decitabine, or combination of HMA with another drug or lost their response to initial therapy with HMA.
* Eastern Cooperative Oncology Group (ECOG) performance status \<=2
* Adequate hepatic (serum total bilirubin \< 1.5 x ULN, Serum glutamic pyruvic transaminase (SGPT) and/or serum glutamate oxaloacetate transaminase (SGOT) \<2.5 x ULN) and renal function (creatinine \< 1.5mg/dL).
* Participants must be willing and able to review, understand, and provide written consent before starting therapy.

Exclusion Criteria:

* Active signs or symptoms of central nervous system (CNS) involvement by malignancy (lumbar puncture \[LP\] not required).
* Prior 7+3 remission induction chemotherapy for MDS or AML
* More than 2 lines of prior non-intensive therapy.
* New York Heart Association (NYHA) class III or IV heart disease, active ischemia or any other uncontrolled cardiac condition such as angina pectoris, clinically significant cardiac arrhythmia on rhythm control strategy or on pacemaker, uncontrolled hypertension (blood pressure \> 160 systolic and \> 110 diastolic not responsive to antihypertensive medication)
* Acute myocardial infarction in the previous 12 weeks (from the start of treatment).
* 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).
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to CPX-351.
* Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Known history of HIV or active hepatitis B or C.
* No major surgery within 2 weeks prior to study enrollment.
* Pregnant or breast feeding
* Male and female participants who are fertile who do not agree to use an effective barrier methods of birth control (i.e. abstinence) to avoid pregnancy while receiving study treatment and for 30 days after last dose of study treatment. Non-childbearing is defined as \> 1 year postmenopausal or surgically sterilized.
* Acute promyelocytic leukemia (APL)