CLAG-GO for Patients With Persistent, Relapsed or Refractory AML

Inclusion Criteria:

1. Adult patients age 18 years or older, with a pathologically confirmed diagnosis ofAML [excluding acute promyelocytic leukemia (APL)] according to WHO criteria. AMLmay be de novo, or following a prior hematologic disease and/or therapy-related.

2. Patients must have relapsed after or be refractory to at least one course of anintensive chemotherapy regimen, for example anthracycline/cytarabine ("7+3" ordaunorubicin and cytarabine liposome). Patients with residual disease on day 13-22of initial induction chemotherapy are eligible, provided the bone marrow cellularityis ≥ 30% AND bone marrow blasts are ≥ 20%. Hypomethylating agents such asazacitidine or decitabine are allowed as a prior therapy, but are not considered anintensive chemotherapy regimen.

3. Eastern Cooperative Oncology Group performance status of 0-2.

4. Any systemic chemotherapy and any radiotherapy must be completed at least 7 daysprior to initiation of protocol therapy, with the exception of hydroxyurea or 6-mercaptopurine for cytoreduction.

5. At least 20% expression of CD33 as determined by flow cytometry orimmunohistochemical staining.

6. Adequate renal function, defined as a serum creatinine less than 1.8 mg/dL.

7. Adequate hepatic function, defined as a direct bilirubin less than 2 times theinstitutional upper limit of normal (ULN) and AST, ALT and Alkaline Phosphatase lessthan 3 times the ULN.

8. Patients who relapse after allogeneic hematopoietic stem cell transplantation areeligible, 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 therapyfor at least 2 weeks.

9. Female patients of childbearing potential must have a negative pregnancy test andagree to use an adequate method of contraception as defined by the protocol. Thismust persist through the treatment period until at least 6 months after the lastdose of chemotherapy or GO.

10. Male subjects who are able to father children and are having intercourse withfemales of childbearing potential must also agree to an acceptable method ofcontraception through the treatment period until at least 3 months after the lastdose of chemotherapy or GO, and must refrain from sperm donation during this period.

11. Ability to give written informed consent.

Exclusion Criteria:

1. Patients with acute promyelocytic leukemia (FAB-M3) or chronic myelogenous leukemiain blast phase.

2. Isolated myeloid sarcoma. Patients must have marrow involvement with AML to enterthe study.

3. Patients with known active AML involvement of the central nervous system.

4. Prior treatment with gemtuzumab ozogamicin or cladribine for AML. Prior treatmentwith cytarabine is permitted.

5. As patients will be receiving G-CSF prior to chemotherapy, patients presenting withsymptomatic leukostasis (as judged by the investigator) are excluded. Hydroxyurea, 6-mercaptopurine and/or leukapheresis for blast count control (see inclusioncriterion #4) for patients with asymptomatic hyperleukocytosis is permitted beforestarting treatment, but must be stopped for at least 24 hours prior to startingprotocol treatment.

6. Active uncontrolled infection. Patients on prophylactic antibacterial, antifungal,and/or antiviral agents and patients whose infections are controlled with theseagents are eligible.

7. Known active hepatitis B or C or other known active hepatic disorder.

8. Any history of veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS).

9. Active concurrent malignancy, unless disease-free for at least 3 years. Subjectswith treated non-melanoma skin cancer, in situ carcinoma or cervical intraepithelialneoplasia, regardless of the disease-free duration, are eligible for this study ifdefinitive treatment for the condition has been completed. Patients withorgan-confined prostate cancer with no evidence of recurrent or progressive diseaseare eligible if hormonal therapy has been initiated or the malignancy has beentreated surgically or with definitive radiotherapy.

10. Uncontrolled intercurrent illness including, but not limited to, symptomaticcongestive heart failure, unstable angina pectoris, cardiac arrhythmia, orpsychiatric illness/social situations that per investigator's judgment would limitcompliance with study requirements.