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

January 14, 2016 updated by: Michael Boyiadzis, University of Pittsburgh

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)

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

5

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • University of Pittsburgh Cancer Institute / Hillman Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Gemtuzumab ozogamicin/Mitoxantrone/Etoposide
Drug: Gemtuzumab ozogamicin
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.
Other Names:
  • Mylotarg®
Drug: Mitoxantrone
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
Other Names:
  • Novantrone®
Drug: Etoposide
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
Other Names:
  • ToposarTM

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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.
Bone marrow biopsy and aspiration 14 days after gemtuzumab ozogamicin administration, to evaluate response to the study drug regimen.

Secondary Outcome Measures

Outcome Measure
Time Frame
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.
Indefinite; subjects are followed for survival.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Pittsburgh

Investigators

  • Principal Investigator: Michael Boyiadzis, MD, University of Pittsburgh

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2008

Primary Completion (Actual)

April 1, 2011

Study Completion (Actual)

April 1, 2011

Study Registration Dates

First Submitted

April 11, 2008

First Submitted That Met QC Criteria

April 11, 2008

First Posted (Estimate)

April 17, 2008

Study Record Updates

Last Update Posted (Estimate)

January 15, 2016

Last Update Submitted That Met QC Criteria

January 14, 2016

Last Verified

January 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 07-154

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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