Arsenic Trioxide and Gemtuzumab Ozogamicin in Treating Patients With Advanced Myelodysplastic Syndromes
RATIONALE: Drugs used in chemotherapy, such as arsenic trioxide and gemtuzumab ozogamicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.
PURPOSE: This phase II trial is studying how well giving arsenic trioxide together with gemtuzumab ozogamicin works in treating patients with advanced myelodysplastic syndromes.
Drug: arsenic trioxide
Drug: gemtuzumab ozogamicin
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Trial of Combination Therapy With Arsenic Trioxide (Trisenox) and Gemtuzumab Ozogamicin (Mylotarg) for the Treatment of Adult Patients With Advanced Myelodysplastic Syndrome|
- Complete and Partial Remission Per the International Working Group (IWG) Criteria for Myelodysplastic Syndromes (MDS) or Acute Myeloid Leukemia (AML) [ Time Frame: at 12 weeks post treatment ] [ Designated as safety issue: No ]The null hypothesis to be tested was the percentage who will respond to combination arsenic trioxide (ATO) and gemtuzumab ozogamicin (GO) therapy is <10%. A total of >/= 9 responses observed in 30 evaluable patients was taken as evidence warranting further study of the regimen, provided the toxicity profile also appears favorable. The IWG Criteria standardizes the clinical responses in MDS and AML based upon hematologic improvement, quality of life and cytogenic improvement. These standardizations allow for the responses to be determined as either complete responses or partial responses.
- Overall Survival [ Time Frame: From date of enrollment to a minimum of three years for survival ] [ Designated as safety issue: No ]Patient's Overall Survival from date of enrollment to a minimum of three years for survival.
- Tolerability [ Time Frame: 12 Weeks ] [ Designated as safety issue: Yes ]Tolerability of Therapy was assessed through use of the National Cancer Institute Common Toxicity Criteria (version 3.0). Treatment tolerability was determined based upon whether or not the physician determined therapy was in the patient's best interest, whether the patient wanted to continue therapy or not, whether patients discontinued treatment due to progressive disease, or whether patients discontinued treatment due to toxicity.
|Study Start Date:||February 2004|
|Study Completion Date:||November 2010|
|Primary Completion Date:||December 2008 (Final data collection date for primary outcome measure)|
Experimental: ATO + GO
Arsenic Trioxide 0.25 mg/kg D1-5 Week 1/Twice Weekly W2-12 + Gemtuzumab Ozogamicin 3 mg/m^2 D8 for 1 or 2 Cycles of 12 Weeks each
Drug: arsenic trioxide
Arsenic trioxide will be administered at a dose of 0.25 mg/kg/day IV over 1-2 hours for 5 consecutive days during the first week. Subsequently, arsenic trioxide will be given at a dose of 0.25mg/kg/day twice a week for 11 additional weeks (weeks 2-12).
Other Name: TrisenoxDrug: gemtuzumab ozogamicin
Gemtuzumab ozogamicin consists of a 2 hr infusion at a dose of 3mg/m2 on day 8 of each 12-week cycle. Gemtuzumab ozogamicin should be administered at a minimum of one hour after the completion of the arsenic trioxide infusion
Other Name: Mylotarg
- Determine the efficacy of arsenic trioxide and gemtuzumab ozogamicin to achieve complete and partial remissions in patients with advanced myelodysplastic syndromes.
- Determine the efficacy of this regimen, in terms of 50% decrease in Red Blood Cell (RBC) transfusion requirements and change in hemoglobin concentration from baseline in patients treated with this regimen.
- Determine the platelet, neutrophil, bone marrow, and cytogenic response in patients treated with this regimen.
- Determine the response duration in patients treated with this regimen.
- Determine the quality of life of patients treated with this regimen.
- Determine the safety and toxicity of this regimen in these patients.
OUTLINE: This is a multicenter, open-label study.
Patients receive arsenic trioxide IV over 1 hour once daily on days 1-5 in week 1 and then twice weekly in weeks 2-12. They also receive gemtuzumab ozogamicin IV over 2 hours on day 8. Treatment repeats every 12 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Quality of life is assessed at baseline, every 12 weeks during study treatment, and then 4 weeks after the completion of study treatment.
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00274781
|United States, Ohio|
|Cleveland Clinic Taussig Cancer Center|
|Cleveland, Ohio, United States, 44195|
|Study Chair:||Mikkael A. Sekeres, MD, MS||The Cleveland Clinic|