Clinical trial NCT00660036: Phase I/II Study of Mitoxantrone, Etoposide and Gemtuzumab Ozogamicin for Acute Myeloid Leukemia
Official title: Phase I/II Study of the Combination of Mitoxantrone, Etoposide and Gemtuzumab Ozogamicin for Patients With Acute Myeloid Leukemia Refractory to Initial Standard Induction Therapy (UPCI 07-154)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Acute Myeloid Leukemia
Keywords: Acute myeloid leukemia
Refractory
Relapsed
Second line
Gemtuzumab ozogamicin
Mitoxantrone
Etoposide
Phase I
Phase II
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
First posted: 2008-04-17
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: To evaluate the toxicity and response rate of the combination therapy of mitoxantrone, etoposide and gemtuzumab ozogamicin as second line therapy in patients with acute myeloid leukemia (AML).
timeFrame: Bone marrow biopsy and aspiration 14 days after gemtuzumab ozogamicin administration, to evaluate response to the study drug regimen.
Secondary outcomes:
measure: To assess the overall survival in patients with AML treated with the combination of mitoxantrone, etoposide and gemtuzumab ozogamicin.
timeFrame: Indefinite; subjects are followed for survival.
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Institute / Hillman Cancer Center
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Michael Boyiadzis, MD
role: PRINCIPAL_INVESTIGATOR
References: