Phase II Study of the Combination of Mitoxantrone, Etoposide and Gemtuzumab Ozogamicin (MEGO) for Patients With Acute Myeloid Leukemia Refractory to Initial Standard Induction Therapy

Prior treatment

• Prior use of mitoxantrone or etoposide or GO.
• Previous allogeneic hematopoietic cell transplantation.
• Patient may have not received any other investigational anti-neoplastic agents within 4 weeks from the start of therapy.
• Concurrent active malignancy; exceptions include patients who have been disease free for 5 years, patients with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma, or patients with another malignancy with better prognosis than AML.

Other illness

• Has known history of active Hepatitis B (HBsAg reactive) or Hepatitis C (detectable HCV RNA).
• Uncontrolled, life-threatening infection that is not responding to antimicrobial therapy.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory or cardiac disease).

Lab values

• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of treating investigator.

Other

• Patients with a diagnosis of Acute Promyelocytic Leukemia (APL) as defined by the World Health Organization.
• Relapsed acute leukemia.
• Bi-lineage or bi-phenotypic leukemia.
• First induction course of acute myeloid leukemia with CPX-351.
• Women who are pregnant or breastfeeding.

• Able to understand and have the ability to provide written consent.
• Age: ≥18 and ≤75 years-old
• Patients with newly diagnosed AML based on the World Health Organization classification who have persistent disease after their first course treatment with an anthracycline and cytarabine (the diagnosis of persistent disease, which is defined as ≥10% blasts by morphology for this trial or \>5% blasts if they have had an increase in blasts from the last bone marrow biopsy, will be based on their assessment after bone marrow aspiration and/or biopsy after initial treatment).
• Patients with myelodysplastic syndrome (MDS) based on the World Health Organization classification who have persistent disease after their treatment with an anthracycline and cytarabine (the diagnosis of persistent disease, which is defined as ≥10% blasts by morphology for this trial or \>5% blasts if they have had an increase in blasts from the last bone marrow biopsy, will be based on their assessment after bone marrow aspiration and/or biopsy after initial treatment).
• CD33 expression in ≥ 30% of leukemic blasts on the bone marrow.
• Eastern Cooperative Oncology Group Performance Status of 0 -2 (see Appendix I).
• Patients must have the following laboratory values prior to beginning protocol treatment:
  • Calculated creatinine clearance ≥ 30 mL/min (using the Cockcroft-Gault equation CL creatinine = ((140-age) x body mass X 0.85 if female)/72 x creatinine where age is given in years, body mass is given in Kg and creatinine is given in mg/dl).
  • Aspartate aminotransferase (AST) ≤ 2.5 x upper normal limit.
  • Alanine aminotransferase (ALT) ≤ 2.5 x upper normal limit.
  • Total bilirubin ≤ 2 x upper normal limit. Note: As many eligible patients will be pancytopenic secondary to their disease or prior treatments, hematologic abnormalities will not be used as criteria for entry or exclusion.
• Left ventricular ejection fraction (LVEF) ≥50 %.
• Females of child-bearing potential must have a negative pregnancy test during screening and all subjects must agree to use an effective method of contraception. A woman is eligible to enter and participate in the study if she is of:
  • Non-childbearing potential (i.e., physiologically incapable of becoming pregnant) including any female who has had a hysterectomy or has had a bilateral oophorectomy (ovariectomy).
  • Childbearing potential, has a negative serum pregnancy test during the screening period and agrees to avoid sexual activity or use contraception from screening through follow-up (method of birth control if the patient is not neutropenic include the use of a diaphragm, intrauterine device, contraceptive sponge and/or usage of male condom with a spermicide from the partner). A man with a female partner of childbearing potential is eligible to enter and participate in the study if he has either had a prior vasectomy or agrees to avoid sexual activity or use adequate contraception (as described above) from screening through follow-up.