Combination Chemotherapy with Gemtuzumab Ozogamicin for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia

Inclusion Criteria

• Patients with a pathologically confirmed diagnosis of AML (excluding acute promyelocytic leukemia [APL]) according to World Health Organization (WHO) criteria. AML may be de novo, or following a prior hematologic disease and/or therapy-related
• Patients must have relapsed after or be refractory to at least one course of an intensive chemotherapy regimen, for example anthracycline/cytarabine (“7+3” or daunorubicin and cytarabine liposome). Patients with residual disease on day 13-22 of initial induction chemotherapy are eligible, provided the bone marrow cellularity is >= 30% AND bone marrow blasts are >= 20%. Hypomethylating agents such as azacitidine or decitabine are allowed as a prior therapy, but are not considered an intensive chemotherapy regimen
• Eastern Cooperative Oncology Group performance status of 0-2
• Any systemic chemotherapy and any radiotherapy must be completed at least 7 days prior to initiation of protocol therapy, with the exception of hydroxyurea or 6-mercaptopurine for cytoreduction
• At least 20% expression of CD33 as determined by flow cytometry or immunohistochemical staining
• Serum creatinine less than 1.8 mg/dL
• Direct bilirubin less than 2 times the institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) less than 3 times the ULN
• Alkaline phosphatase less than 3 times the ULN
• Patients who relapse after allogeneic hematopoietic stem cell transplantation are eligible, provided they are at least 60 days from stem cell infusion, do not have > grade 1 graft versus host disease, and have been off all immunosuppressive therapy for at least 2 weeks
• Female patients of childbearing potential must have a negative pregnancy test and agree to use an adequate method of contraception as defined by the protocol. This must persist through the treatment period until at least 6 months after the last dose of chemotherapy or GO
• Male subjects who are able to father children and are having intercourse with females of childbearing potential must also agree to an acceptable method of contraception through the treatment period until at least 3 months after the last dose of chemotherapy or GO, and must refrain from sperm donation during this period
• Ability to give written informed consent

Exclusion Criteria

• Patients with acute promyelocytic leukemia (FAB-M3) or chronic myelogenous leukemia in blast phase
• Isolated myeloid sarcoma. Patients must have marrow involvement with AML to enter the study
• Patients with known active AML involvement of the central nervous system
• Prior treatment with gemtuzumab ozogamicin or cladribine for AML. Prior treatment with cytarabine is permitted
• As patients will be receiving granulocyte-colony stimulating factor (G-CSF) prior to chemotherapy, patients presenting with symptomatic leukostasis (as judged by the investigator) are excluded. Hydroxyurea, 6-mercaptopurine and/or leukapheresis for blast count control for patients with asymptomatic hyperleukocytosis is permitted before starting treatment, but must be stopped for at least 24 hours prior to starting protocol treatment
• Active uncontrolled infection. Patients on prophylactic antibacterial, antifungal, and/or antiviral agents and patients whose infections are controlled with these agents are eligible
• Known active hepatitis B or C or other known active hepatic disorder
• Any history of veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS)
• Active concurrent malignancy, unless disease-free for at least 3 years. Subjects with treated non-melanoma skin cancer, in situ carcinoma or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed. Patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease are eligible if hormonal therapy has been initiated or the malignancy has been treated surgically or with definitive radiotherapy
• Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that per investigator’s judgment would limit compliance with study requirements