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

Sponsored by:	University of Pittsburgh
Information provided by:	University of Pittsburgh
ClinicalTrials.gov Identifier:	NCT00660036

Purpose

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.

Condition	Intervention	Phase
Acute Myeloid Leukemia	Drug: Gemtuzumab ozogamicin Drug: Mitoxantrone Drug: Etoposide	Phase I Phase II

MedlinePlus related topics: Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Etoposide Mitoxantrone hydrochloride Mitoxantrone Gemtuzumab ozogamicin Etoposide phosphate Sodium chloride Chlorides

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Single Group Assignment, Safety/Efficacy Study
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)

Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:

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). [ Time Frame: Bone marrow biopsy and aspiration 14 days after gemtuzumab ozogamicin administration, to evaluate response to the study drug regimen. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To assess the overall survival in patients with AML treated with the combination of mitoxantrone, etoposide and gemtuzumab ozogamicin. [ Time Frame: Indefinite; subjects are followed for survival. ] [ Designated as safety issue: No ]

Estimated Enrollment:	56
Study Start Date:	September 2008
Estimated Study Completion Date:	April 2011
Estimated Primary Completion Date:	April 2010 (Final data collection date for primary outcome measure)

Intervention Details:

On Day 6 of an inpatient hospital stay: Based on the study design patients will be treated with one of three doses (3 mg/m^2, 6 mg/m^2 or 9 mg/m^2), administered intravenously in 100 ml of 0.9% sodium chloride over 2 hours.

On Days 1-3 of an inpatient hospital stay: 10 mg/m^2 administered via IVPB (intravenous piggy-back) in 50ml normal saline (NS) over 15 minutes

On Days 1-5 of an inpatient hospital stay: 100 mg/m^2 administered intravenously in 500 ml of 0.9% sodium chloride over 2 hours

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

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00660036

Contacts

Contact: Michael Boyiadzis, MD

412-648-6589

boyiadzism@upmc.edu

Locations

United States, Pennsylvania
University of Pittsburgh Cancer Institute / Hillman Cancer Center	Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Principal Investigator: Michael Boyiadzis, MD
Sub-Investigator: Kenneth Foon, MD
Sub-Investigator: Mounzer Agha, MD
Sub-Investigator: Anastasios Raptis, MD
Sub-Investigator: Preet M. Chaudhary, MD, PhD
Sub-Investigator: Suzanne Lentzsch, MD, PhD
Sub-Investigator: Markus Y. Mapara, MD, PhD
Sub-Investigator: David Roodman, MD, PhD
Sub-Investigator: Roy Smith, MD
Sub-Investigator: Ahmad A. Tarhini, MD, MSc
Sub-Investigator: Robert L. Redner, MD
Sub-Investigator: Jing-Zhou Hou, MD

Sponsors and Collaborators

University of Pittsburgh

Investigators

Principal Investigator:

Michael Boyiadzis, MD

University of Pittsburgh

More Information

Responsible Party:	University of Pittsburgh ( Michael Boyiadzis, MD )
Study ID Numbers:	07-154
Study First Received:	April 11, 2008
Last Updated:	October 3, 2008
ClinicalTrials.gov Identifier:	NCT00660036
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Pittsburgh:

Acute myeloid leukemia
Refractory
Relapsed
Second line
Gemtuzumab ozogamicin

Mitoxantrone
Etoposide
Phase I
Phase II

Study placed in the following topic categories:

Antibodies, Monoclonal
Leukemia
Antibodies
Acute myelogenous leukemia
Mitoxantrone
Leukemia, Myeloid

Gemtuzumab
Leukemia, Myeloid, Acute
Etoposide phosphate
Etoposide
Acute myelocytic leukemia
Immunoglobulins

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Histologic Type
Immunologic Factors
Sensory System Agents
Antineoplastic Agents
Therapeutic Uses

Physiological Effects of Drugs
Peripheral Nervous System Agents
Analgesics
Central Nervous System Agents
Antineoplastic Agents, Phytogenic
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 15, 2009