Mitoxantrone, Etoposide, and Gemtuzumab Ozogamicin in Treating Patients with Refractory Acute Myeloid Leukemia

Status: Active


This phase II trial studies the side effects of mitoxantrone, etoposide, and gemtuzumab ozogamicin and to see how well they work in treating patients acute myeloid leukemia that does not respond to initial standard induction therapy. Drugs used in chemotherapy, such as mitoxantrone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Etoposide may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Gemtuzumab ozogamicin is a monoclonal antibody, gemtuzumab, linked to a toxic agent called ozogamicin. Gemtuzumab attaches to CD33 positive cancer cells in a targeted way and delivers ozogamicin to kill them. This study is being done to see if the combination of mitoxantone, etoposide, and gemtuzumab ozogamicin improves the response rate in patients with acute myeloid leukemia that did not respond after a course of induction chemotherapy.

Eligibility Criteria

Inclusion Criteria

  • Able to understand and have the ability to provide written consent
  • 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, will be based on their assessment after bone marrow aspiration and/or biopsy after initial treatment). The bone marrow aspiration and/or biopsy will be evaluated by the Hematopathology Division of the University of Pittsburgh. In order to prevent any delays in starting therapy for eligible patients, a preliminary evaluation of the bone marrow will be sent by the hematopathologist via e-mail to the investigator
  • CD33 expression in >= 30% of leukemic blasts on the bone marrow
  • Eastern Cooperative Oncology Group performance status of 0-2
  • Calculated creatinine clearance >= 30 mL/min (using the Cockcroft-Gault equation clearance) (prior to beginning protocol treatment)
  • Aspartate aminotransferase (AST) =< 2.5 x upper normal limit (prior to beginning protocol treatment)
  • Alanine aminotransferase (ALT) =< 2.5 x upper normal limit (prior to beginning protocol treatment)
  • Total bilirubin =< 2 x upper normal limit (prior to beginning protocol treatment) * 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

Exclusion Criteria

  • 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
  • Prior use of mitoxantrone or etoposide or gemtuzumab ozogamicin (GO)
  • Previous allogeneic or autologous hematopoietic cell transplantation or solid organ transplantation
  • First induction course of acute myeloid leukemia with liposome-encapsulated daunorubicin-cytarabine (CPX-351)
  • Prior use of a FLT3 inhibitor
  • 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
  • Has known history of active hepatitis B (hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (detectable hepatitis C virus [HCV] ribonucleic acid [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
  • 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 that is indolent or definitively treated
  • Women who are pregnant or breastfeeding
  • Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory or cardiac disease)

Locations & Contacts


University of Pittsburgh Cancer Institute (UPCI)
Status: Active
Contact: Michael Boyiadzis
Phone: 412-648-6589

Trial Objectives and Outline


I. To evaluate the response rate and toxicity of the combination of mitoxantrone hydrochloride (mitoxantrone), etoposide and gemtuzumab ozogamicin as second line therapy in patients with acute myeloid leukemia (AML) who have failed the first induction therapy.


I. To assess the progression-free survival, overall survival and treatment related mortality in patients with AML treated with the combination of mitoxantrone, etoposide and gemtuzumab ozogamicin.

II. To explore if age, cytogenetic status, percent of blast in the bone marrow prior to therapy or percent expression of CD33 in the leukemia blasts are predictive of complete remission, overall survival or progression-free survival in patients with AML treated with the combination of mitoxantrone, etoposide and gemtuzumab ozogamicin.


Patients receive mitoxantrone hydrochloride intravenously (IV) over 15 minutes on days 1-5, etoposide IV over 2 hours on days 1-5, and gemtuzumab ozogamicin IV over 2 hours on day 6 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically for up to 5 years.

Trial Phase & Type

Trial Phase

Phase II

Trial Type


Lead Organization

Lead Organization
University of Pittsburgh Cancer Institute (UPCI)

Principal Investigator
Michael Boyiadzis

Trial IDs

Primary ID 18-111
Secondary IDs NCI-2019-02782 ID NCT03839446