RATIONALE: Monoclonal antibodies such as gemtuzumab ozogamicin can locate tumor cells and
either kill them or deliver tumor-killing substances to them without harming normal cells.
Oblimersen may help gemtuzumab ozogamicin kill more cancer cells by making cancer cells more
sensitive to the drug.
PURPOSE: Phase II trial to study the effectiveness of combining oblimersen and gemtuzumab
ozogamicin in treating older patients who have relapsed acute myeloid leukemia.
- Determine the complete response rate of elderly patients with relapsed CD33-positive
acute myeloid leukemia treated with oblimersen and gemtuzumab ozogamicin.
- Determine the overall response rate and duration of response of patients treated with
- Determine the safety of this regimen in these patients.
OUTLINE: This is a multicenter study.
Patients receive oblimersen IV continuously on days 1-7 and 15-22 and gemtuzumab ozogamicin
IV over 2 hours on days 4 and 18.
Patients are followed monthly for 6 months.
PROJECTED ACCRUAL: A total of 20-100 patients will be accrued for this study within 1 year.
- Histologically confirmed CD33+ acute myeloid leukemia (AML)
- In first relapse from chemotherapy
- Complete response lasting at least 3 months before relapse
- No CNS leukemia
- No secondary leukemia or history of antecedent hematologic disorder prior to initial
onset of AML (e.g., myelodysplasia)
- 60 and over
- ECOG 0-2
- Not specified
- WBC less than 30,000/mm^3
- No bleeding or coagulation disorder except disease-related disseminated intravascular
- Bilirubin no greater than 1.5 mg/dL
- PT and PTT no greater than 1.5 times upper limit of normal OR
- INR no greater than 1.3
- No history of chronic hepatitis or cirrhosis
- Creatinine no greater than 2.0 mg/dL
- No uncontrolled congestive heart failure
- No New York Heart Association class III or IV heart disease
- No severe pulmonary disease
- HIV negative
- No other concurrent medical disease that would preclude study entry
- No known hypersensitivity to phosphorothioate-containing oligonucleotides, gemtuzumab
ozogamicin or any of its components, E. coli protein, or any product produced in E.
- No other concurrent malignancy
- No known human anti-human antibodies
- No uncontrolled seizure disorder
- No active uncontrolled infection
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
- No prior allogeneic or autologous stem cell transplantation
- No prior therapy with an anti-CD33 antibody (e.g., gemtuzumab ozogamicin or M195)
- See Disease Characteristics
- At least 2 weeks since prior cancer chemotherapy except intrathecal chemotherapy or
- Not specified
- At least 2 weeks since prior systemic radiotherapy
- At least 2 weeks since prior major surgery
- No prior organ allograft
- At least 3 weeks since prior antileukemic therapy and recovered
- No other concurrent investigational therapy
- No concurrent immunosuppressive therapy