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

NeuroTherapia, Inc.

Status and phase

Completed

Phase 2

Conditions

Leukemia

Myelodysplastic Syndromes

Treatments

Drug: gemtuzumab ozogamicin

Drug: arsenic trioxide

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00274781

P30CA043703 (U.S. NIH Grant/Contract)

CCF6818

CCF-6818 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

30 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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