Phase I Study of Mitoxantrone and Etoposide Combined With Hydroxychloroquine, for Relapsed Acute Myelogenous Leukemia

Inclusion Criteria:

1. Able to understand and have the ability to provide written consent
2. Age > 18 years old to <80 years old
3. Patients with AML in the first morphologic relapse as defined by >5% reappearance of leukemia blasts in the bone marrow not attributable to any other cause (Appendix I) who have not yet received chemotherapy for the current relapse
4. Eastern Cooperative Oncology Group Performance Status of 0 -2 (see Appendix II)

5. Adequate organ function

   1. Serum creatinine ≤ 1.5 mg/dl and calculated creatinine clearance ≥ 50 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)
   2. Aspartate aminotransferase (AST) ≤ 5x the upper limit of normal Alanine aminotransferase (ALT) < 5x the upper limit of normal
   3. Direct bilirubin ≤ 1.5 mg/dl Note: As many eligible patients will be pancytopenic secondary to their disease or prior treatments, hematologic abnormalities will not be used as a criteria for entry or exclusion
6. Left ventricular ejection fraction (LVEF) ≥50 %

7. 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:

   1. 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).
   2. Childbearing potential, has a negative serum pregnancy test during the screening period and agrees to avoid sexual activity or use accepted methods of contraception from screening through follow-up.

Men with a female partner of childbearing potential are eligible to enroll and participate in the study if they have had either a prior vasectomy or agree to avoid sexual activity or use appropriate barrier contraception from screening through post-treatment follow-up.

Exclusion Criteria:

1. Acute promyelocytic leukemia
2. Prior chemotherapy regimen given for 1st relapse, not including the use of hydroxyurea or plasmapheresis that is used prior to the initiation of chemotherapy.
3. Previous use of mitoxantrone and etoposide combination therapy within the preceding 180 days of screening.
4. Symptomatic central nervous system (CNS) involvement
5. Uncontrolled, life-threatening infection that is not responding to antimicrobial therapy
6. History of psychiatric disorder which may compromise compliance with the protocol or which does not allow for appropriate informed consent
7. Current receiving any other anti neoplastic investigational agents
8. Prior autologous or allogeneic stem cell transplantation
9. Concurrent malignancy. Exceptions: Patients who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible. Subjects with concurrent malignancies that are indolent or definitely treated may be enrolled.
10. Women who are pregnant or breastfeeding
11. Evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory or cardiac disease)
12. Inability to take oral medications, due to impaired swallowing ability or poor absorption capacity
13. Known glucose-6-phosphate dehydrogenase (G-6PD) deficiency