CPX-351 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome
Condition: Adult Acute Erythroid Leukemia (M6); Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Leukemia, Monocytic, Acute; Leukemia, Myelomonocytic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Erythroblastic, Acute; Myelodysplastic Syndromes; Syndrome
Intervention: liposomal cytarabine-daunorubicin CPX-351
Intervention description: Given IV
Intervention MeSH terms: Cytarabine; Daunorubicin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 60 Years
Healthy volunteers: No

Summary:

      This phase 2 clinical trial studies how well CPX-351 (liposomal cytarabine-daunorubicin)
      works in treating patients with relapsed or refractory acute myeloid leukemia or
      myelodysplastic syndrome. Drugs used in chemotherapy, such as CPX-351, work in different ways
      to stop the growth of cancer cells, either by killing the cells or by stopping them from
      dividing.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Ability to understand and voluntarily give informed consent

          -  Age ≥ 60

          -  Pathological diagnosis of AML (by WHO criteria) or higher risk MDS (includes int-2 and
             high risk MDS by IPSS) along with one of the following:

               -  Patients with de novo or secondary MDS with progression/refractoriness after HMA
                  treatment who have not transformed to AML

               -  Patients with MDS and prior HMA treatment for MDS who transform to AML

               -  Patients with AML who are refractory/relapsed after HMA therapy for their AML are
                  eligible

          -  Life expectancy > 1 month

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2

          -  Able to adhere to the study visit schedule and other protocol requirements

          -  Laboratory values fulfilling the following:

               -  Serum creatinine < 2.0 mg/dL

               -  Serum total bilirubin ≤ 2.5 mg/dL. Note, patients with Gilbert's syndrome may
                  have elevated bilirubin at baseline prior to diagnosis with AML or MDS. Patients
                  with Gilbert's syndrome are included if their total bilirubin is ≤ 2 times their
                  baseline total bilirubin.

               -  Serum alanine aminotransferase or aspartate aminotransferase < 3 times ULN

          -  Cardiac ejection fraction ≥ 45% by echocardiography (transthoracic echocardiography)
             or MUGA scan

          -  Patients with second malignancies may be eligible at discretion of PI given acute life
             threatening nature of untreated AML or higher risk MDS. Patients maintained on
             long-term non-chemotherapy treatment, e.g., hormonal therapy, are also eligible.

        Exclusion Criteria:

          -  Patients who have previously undergone allogeneic hematopoietic stem cell transplant
             will be excluded from this study

          -  Patients who have previously had > 368 mg/m2 cumulative dose of daunorubicin or > 368
             mg/m2 daunorubicin-equivalent anthracycline therapy (for example, from prior treatment
             of solid tumors). See appendix for anthracycline equivalence table.

          -  Acute promyelocytic leukemia [t(15;17)]

          -  Any serious medical condition, laboratory abnormality or psychiatric illness that
             would prevent obtaining informed consent

          -  Patients who have had conventional intensive cytotoxic induction chemotherapy for
             treatment of specifically MDS or AML are excluded.

          -  Patients who have not previously been treated with HMA therapy will be excluded

          -  Clinical evidence of active CNS leukemia

          -  Patients with evidence of uncontrolled current myocardial impairment (e.g. unstable
             ischemic heart disease, uncontrolled arrhythmia, symptomatic valvular dysfunction not
             controlled on medical therapy, uncontrolled hypertensive heart disease, and
             uncontrolled congestive heart failure)

          -  Active and uncontrolled infection. Patients with an active infection receiving
             treatment and hemodynamically stable for 48 hours may be entered into the study

          -  Known active uncontrolled HIV or hepatitis C infection

          -  Known hypersensitivity to cytarabine, daunorubicin or liposomal products

          -  Known history of Wilson's disease or other copper-related disorders

          -  Other medical or psychiatric illness or organ dysfunction or laboratory abnormality
             which in the opinion of the investigator would compromise the patient's safety or
             interfere with data interpretation

          -  Laboratory abnormalities:

               -  Serum creatinine ≥ 2.0 mg/dL

               -  Serum total bilirubin > 2.5 mg/dL. Note, patients with Gilbert's syndrome may
                  have elevated bilirubin at baseline prior to diagnosis with AML or MDS. Patients
                  with Gilbert's syndrome are excluded if their total bilirubin is > 2 times their
                  baseline total bilirubin.

               -  Serum alanine aminotransferase or aspartate aminotransferase > 3 times ULN