Arsenic Trioxide and Gemtuzumab Ozogamicin in Treating Patients With Advanced Myelodysplastic Syndromes

NCT ID: NCT00274781

Last Updated: 2015-07-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-02-29
• Study Completion Date: 2010-11-30

Brief Summary

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.

Detailed Description

OBJECTIVES:

Primary

• Determine the efficacy of arsenic trioxide and gemtuzumab ozogamicin to achieve complete and partial remissions in patients with advanced myelodysplastic syndromes.

Secondary

• 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.

Conditions

Leukemia; Myelodysplastic Syndromes

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

arsenic trioxide

Intervention Type: DRUG

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).

gemtuzumab ozogamicin

Intervention Type: DRUG

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

Interventions

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).

Intervention Type: DRUG

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

Intervention Type: DRUG

Other Intervention Names

Trisenox; Mylotarg

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of one of the following hematologic malignancies:

• Myelodysplastic syndromes (MDS) of one of the following French-American-British (FAB) classifications:

• Refractory anemia with excess blasts (RAEB) (WHO RAEB-1)
• RAEB in transformation (RAEB-t) (RAEB-2)
• Chronic myelomonocytic leukemia (CMML) with > 5% myeloblasts (WHO CMML-2)
• International Prognostic Scoring System (IPSS) score of intermediate-2 or higher in the setting of > 5% myeloblasts
• Acute myeloid leukemia that has evolved from MDS
• Must not be a candidate for bone marrow transplantation as first-line therapy or must have declined bone marrow transplantation

PATIENT CHARACTERISTICS:

• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Life expectancy of at least 4 months
• Serum potassium ≥ 4.0 milliequivalent (mEq/dL) and serum magnesium ≥ 1.8 mg/dL (supplemental electrolytes allowed)
• Absolute corrected QT interval (QTc) interval < 460 msec
• No serious medical condition, laboratory abnormality, or psychiatric illness that, in the view of the treating physician, would place the patient at an unacceptable risk if he or she were to participate in the study or would prevent that person from giving informed consent
• Not pregnant or nursing
• Fertile patients must be willing to use adequate contraception (barrier method with spermicidal jelly, intrauterine device (IUD), or oral contraceptives)
• Negative pregnancy test
• Creatinine > 2.5 mg/dL
• serum glutamate oxaloacetate transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) > 1.5 times upper limit of normal
• Bilirubin > 2.0 mg/dL
• No history of malignancy within the past 3 years other than MDS except basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast
• Arsenic trioxide is contraindicated in patients who are hypersensitive to arsenic

PRIOR CONCURRENT THERAPY:

• No prior bone marrow transplantation
• Must not receive another investigational or approved therapy for MDS within 4 weeks of study enrollment, including growth factors (within 1 week of study enrollment)
• No prior arsenic trioxide or gemtuzumab ozogamicin
• No other concurrent cytotoxic drugs or investigational agents

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Michigan

OTHER

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

The Cleveland Clinic

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mikkael A. Sekeres, MD, MS

Role: STUDY_CHAIR

The Cleveland Clinic

Locations

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States

Countries

United States

Other Identifiers

P30CA043703

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CCF-6818

Identifier Type: OTHER

Identifier Source: secondary_id

CCF6818

Identifier Type: -

Identifier Source: org_study_id