Phase I/II Study of Mitoxantrone, Etoposide and Gemtuzumab Ozogamicin for Acute Myeloid Leukemia

University of Pittsburgh

Status and phase

Terminated

Phase 1

Conditions

Acute Myeloid Leukemia

Treatments

Drug: Gemtuzumab ozogamicin

Drug: Etoposide

Drug: Mitoxantrone

Study type

Interventional

Funder types

Other

Identifiers

NCT00660036

07-154

Details and patient eligibility

About

The purpose of this study is to investigate the combination of gemtuzumab ozogamicin, mitoxantrone and etoposide as second line therapy in patients with acute myeloid leukemia.

Full description

The combination of mitoxantrone and etoposide is an active regimen in refractory/relapsed AML patients. In order to improve the efficacy of mitoxantrone and etoposide as second line therapy in patients with AML we proposed to conduct a phase I/II clinical trial combining gemtuzumab ozogamicin with mitoxantrone and etoposide. The phase I portion of the trial will determine the maximum tolerated dose of gemtuzumab ozogamicin combined with mitoxantrone and etoposide and the phase II portion of the trial will determine the efficacy and safety of the combined regimen in patients with AML.

Enrollment

5 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Able to understand and have the ability to provide written consent
Between 18 and 70 years of age
Patients with CD33 positive (determined as CD33 expression in ≥ 20% of leukemic blasts) de novo AML that did not respond to first line induction therapy
ECOG Performance Status of 0-2
Patients must have the following laboratory values within 48 hours prior to beginning protocol treatment: Serum creatinine ≤ 1.5 mg/ml and calculated creatinine clearance ≥ 50mL/min (using the Cockcroft-Gault equation); AST ≤ 59 IU/L; ALT ≤ 72 IU/L; Total bilirubin ≤ 1.3 mg/ml; Note: Hematologic abnormalities will not be used as a criteria for entry or exclusion.
Patients must have 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.

Exclusion criteria

Patients with acute promyelocytic leukemia
Prior use of mitoxantrone or etoposide or gemtuzumab ozogamicin
Antecedent hematologic disorder preceding initial presentation of AML or therapy related AML
History of thromboembolic event within the past 12 months
Hepatitis B or C or HIV positive serology
Symptomatic central nervous system (CNS) involvement
History of congestive heart failure
Myocardial infarction in the past 6 months
Uncontrolled, life-threatening infection that is not responding to antimicrobial therapy
History of psychiatric disorder which may compromise compliance with the protocol or which does not allow for appropriate informed consent
Patient may not be receiving any other anti neoplastic investigational agents
INR> 1.5 or patient is receiving systemic anticoagulation (e.g warfarin)
Patient undergone autologous or allogeneic stem cell transplantation
Other active malignancies except for non-melanoma skin cancer or cervical intraepithelial neoplasia
Women who are pregnant or breastfeeding.