Inclusion Criteria:

1. Patients must have cytologically (or by flow cytometry) documented
relapsed/refractory Acute Myeloid leukemia or Acute Lymphoid leukemia for which no
standard therapy is anticipated to result in a durable remission. Chronic Myeloid
leukemia in blast crisis who progress through Gleevec® or is intolerant to Gleevec®
or other FDA approved BCR-ABL Tyrosine Kinase Inhibitors. Patients with untreated AML
or ALL who are electing not to receive standard therapy are also eligible.
Relapsed/refractory leukemia patients may combination after 1 course of chemotherapy.
In addition,leukemia secondary to pre-existing hematologic disorders high-grade
myelodysplastic syndromes are also eligible.

2. ≥18 years of age.

3. Patients must be informed of the investigational nature of this study and must give
written informed consent in accordance with institutional and federal guidelines.

Patients who cannot provide informed consent will not be eligible for the study.

4. Prior radiotherapy, chemotherapy or biologic therapies are allowed. Previous line(s)
of systemic chemotherapy should have been completed at least 2 weeks prior to
starting protocol treatment. Concurrent hydroxyurea administration will be allowed to
control WBC count, platelet count, or symptoms and will be discontinued 24 hours
prior to the first APLIDIN® dose. For patients with CML in blast crisis, Gleevec® or
other BCR-ABL Tyrosine Kinase Inhibitors must be stopped at least 7 days prior to the
first APLIDIN® dose. t.

5. Patients must have an ECOG performance status ≤2 (Appendix C).

6. Laboratory data:

- Serum Total Bilirubin < 1.5 mg/dL X institutional ULN (except when Gilbert
syndrome is clearly documented and other LFTs are normal).

- AST (SGOT)/ALT (SGPT)/ALKP ≤ 2.5 X institutional ULN.

- Creatinine clearance > 40 ml/min, calculated according to Cockcroft and Gault's
formula (Appendix D).

7. Negative pregnancy test for women of childbearing potential.

8. Bone Marrow Assessment within two weeks before the first Aplidin® administration.

9. Estimated life expectancy of > 1 month.

10. Left ventricular ejection fraction within normal limits.

Exclusion Criteria:

1. Previous treatment with Plitidepsin.

2. Prior autologous and/or allogeneic hematopoietic stem cell transplantation (HSCT)
patients are not eligible due to higher risk of toxicity related to treatment after
such procedure.

3. Active or metastatic secondary primary malignancy.

4. Patients with known Central Nervous System involvement will be excluded from this
clinical trial because of their poor prognosis and because they often develop
progressive neurologic dysfunction that would confound the evaluation of neurologic
and other adverse events.

5. Serious concomitant systemic disorders that would compromise the safety of the
patient or compromise the patient's ability to complete the study, including the
following specific conditions:

- Uncontrolled psychiatric illness or medical illness that the principle
investigator feels will compromise the patient's tolerance of the study
medication.

- Significant non-neoplastic liver disease (e.g., cirrhosis, active chronic
hepatitis).

- Uncontrolled endocrine diseases (e.g. diabetes mellitus, hypothyroidism or
hyperthyroidism) (i.e. requiring relevant changes in medication within the last
month, or hospital admission within the last 3 months).

- Uncontrolled systemic infection.

6. Other relevant cardiac conditions:

- History or presence of unstable angina, myocardial infarction, valvular heart
disease or congestive heart failure.

- Previous mediastinal radiotherapy.

- Uncontrolled arterial hypertension despite optimal medical therapy.

- Previous treatment with doxorubicin at cumulative doses in excess of 400 mg/m².

- Any grade of cardiac arrhythmia according to CTCAE v3.0 (see appendix F) with
exception of < grade 3 supraventricular tachycardia proven to be in response to
medical conditions as anemia, fever, etc. from his/her underlying leukemia.

7. History of hypersensitivity reaction to cremophor, Cytarabine, Mannitol, or
Plitidepsin (Aplidin®).

8. Myopathy or any clinical situation that causes significant and persistent elevation
of CK (> 2.5 ULN in two different determinations performed with one week apart).

9. History of significant Cytarabine related neurotoxicity.

10. Grade >2 motor or sensory neuropathy of any cause.

11. Men and women of reproductive potential who are not using effective contraceptive
methods. The effects of Plitidepsin on the developing human fetus at the recommended
therapeutic dose are unknown. For this reason, women of child-bearing potential and
men must agree to use adequate contraception (hormonal or barrier method of birth
control; abstinence) prior to study entry, for the duration of study participation
and for 6 months after. Should a woman become pregnant or suspect she is pregnant
while participating in this study, she should inform her treating physician
immediately. Also, if the wife or female partner of a male patient becomes pregnant
during the study, the investigator must be notified promptly and the pregnant woman
will be referred for appropriate follow-up with a High-risk Obstetrician.

12. Pregnant and/or lactating women.

13. Patients with immune deficiency are at increased risk of lethal infections when
treated with marrow-suppressive therapy, therefore, known HIV-positive patients with
active HIV infection and/or receiving combination anti-retroviral therapy are
excluded from the study because of possible pharmacokinetic interactions with
Plitidepsin or other agents administered during the study. HIV testing is not
required unless infection is clinically suspected.

14. Known active HBV or HCV infection. Patients with any serological evidence of current
or past hepatitis B exposure are excluded unless the serological findings are clearly
due to vaccination. HBV or HCV testing are not required unless infection is
clinically suspected.

15. Concomitant therapy with therapeutic dose of coumadin is not permitted. A suboptimal
dose for permeability venous access devices is allowed.

16. Treatment with any investigational product in the 30 days period before inclusion in
the study. Wash-out periods since the end of the precedent therapy less than:

- 6 weeks for nitrosoureas or high dose chemotherapy.

- 2 weeks for other chemotherapies or biological agents.

- 4 weeks for radiation or radionuclide therapy (6 weeks in case of prior
extensive external beam radiation, more than 25% of bone marrow distribution).

- 24 hours for hydroxyurea.

- 7 days for Gleevec® or other BCL-ABL tyrosine Kinase inhibitors.

17. Limitation of the patient´s ability to comply with the treatment or follow-up
protocol.