Phase I/II Study of Mitoxantrone, Etoposide and Gemtuzumab Ozogamicin for Acute Myeloid Leukemia
Primary Purpose
Acute Myeloid Leukemia
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Gemtuzumab ozogamicin
Mitoxantrone
Etoposide
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring Acute myeloid leukemia, Refractory, Relapsed, Second line, Gemtuzumab ozogamicin, Mitoxantrone, Etoposide, Phase I, Phase II
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.
Sites / Locations
- University of Pittsburgh Cancer Institute / Hillman Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Gemtuzumab ozogamicin/Mitoxantrone/Etoposide
Arm Description
Outcomes
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).
Secondary Outcome Measures
To assess the overall survival in patients with AML treated with the combination of mitoxantrone, etoposide and gemtuzumab ozogamicin.
Full Information
NCT ID
NCT00660036
First Posted
April 11, 2008
Last Updated
January 14, 2016
Sponsor
University of Pittsburgh
1. Study Identification
Unique Protocol Identification Number
NCT00660036
Brief Title
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
2. Study Status
Record Verification Date
January 2016
Overall Recruitment Status
Terminated
Why Stopped
due to new safety information
Study Start Date
September 2008 (undefined)
Primary Completion Date
April 2011 (Actual)
Study Completion Date
April 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Pittsburgh
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia
Keywords
Acute myeloid leukemia, Refractory, Relapsed, Second line, Gemtuzumab ozogamicin, Mitoxantrone, Etoposide, Phase I, Phase II
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
5 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Gemtuzumab ozogamicin/Mitoxantrone/Etoposide
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Gemtuzumab ozogamicin
Other Intervention Name(s)
Mylotarg®
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Mitoxantrone
Other Intervention Name(s)
Novantrone®
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Etoposide
Other Intervention Name(s)
ToposarTM
Intervention Description
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
Primary Outcome Measure Information:
Title
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.
Secondary Outcome Measure Information:
Title
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.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Boyiadzis, MD
Organizational Affiliation
University of Pittsburgh
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Pittsburgh Cancer Institute / Hillman Cancer Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Phase I/II Study of Mitoxantrone, Etoposide and Gemtuzumab Ozogamicin for Acute Myeloid Leukemia
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