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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2011 by University of Pittsburgh.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT00660036
First received: April 11, 2008
Last updated: April 28, 2011
Last verified: April 2011
  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 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


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 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    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 Name: 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 Name: 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 Name: ToposarTM
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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: Mounzer Agha, MD         
Sub-Investigator: Anastasios Raptis, MD         
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

No publications provided

Responsible Party: Michael Boyiadzis, MD, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT00660036     History of Changes
Other Study ID Numbers: 07-154
Study First Received: April 11, 2008
Last Updated: April 28, 2011
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

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia
Neoplasms by Histologic Type
Neoplasms
Etoposide
Mitoxantrone
Etoposide phosphate
Gemtuzumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 22, 2014