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

Sponsor

University of Pittsburgh (Other)

Overall Status

Terminated

CT.gov ID

NCT00660036

Collaborator

(none)

Enrollment

Location

Arm

30.9

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia	Drug: Gemtuzumab ozogamicin Drug: Mitoxantrone Drug: Etoposide	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

5 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (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)

Study Start Date :

Sep 1, 2008

Actual Primary Completion Date :

Apr 1, 2011

Actual Study Completion Date :

Apr 1, 2011

Arms and Interventions

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

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

Outcome Measures

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). [Bone marrow biopsy and aspiration 14 days after gemtuzumab ozogamicin administration, to evaluate response to the study drug regimen.]

Secondary Outcome Measures

To assess the overall survival in patients with AML treated with the combination of mitoxantrone, etoposide and gemtuzumab ozogamicin. [Indefinite; subjects are followed for survival.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.