Arsenic Trioxide and Gemtuzumab Ozogamicin in Treating Patients With Advanced Myelodysplastic Syndromes
Condition: Leukemia; Myelodysplastic Syndromes
MeSH terms: Leukemia; Preleukemia; Myelodysplastic Syndromes; Syndrome
Intervention: arsenic trioxide; gemtuzumab ozogamicin
Intervention description: 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 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 MeSH terms: Arsenic Trioxide; Gemtuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: refractory anemia with excess blasts in transformation; refractory anemia with excess blasts; chronic myelomonocytic leukemia; secondary acute myeloid leukemia; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; de novo myelodysplastic syndromes

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.
    

Eligibility 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