Randomized Phase II Trial With Infliximab (Remicade) in Patients With Myelodysplastic Syndrome and a Relatively Low Risk of Developing Acute Leukemia
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Confirmed diagnosis (within the past month) of low- or intermediate-risk
myelodysplastic syndromes (MDS) meeting all of the following criteria:
- No more than 10% bone marrow blasts (corresponding to refractory anemia [RA], RA
with ringed sideroblasts, or RA with excess blasts)
- Meets at least 1 of the following hematopoietic criteria:
- Hemoglobin no greater than 10 g/dL OR red blood cell transfusion dependent
- Neutrophil count no greater than 1,500/mm^3
- Platelet count no greater than 100,000/mm^3 OR platelet transfusion
dependent
- No poor cytogenetics (complex abnormalities or involvement of chromosome 7)
- Patients with unknown cytogenetics may be eligible provided reasonable
efforts have been made for determining the cytogenetic profile and the
results are considered a failure (e.g., normal karyotype [NN] with no more
than 10 metaphases)
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- WHO 0-2
Life expectancy
- Not specified
Hematopoietic
- See Disease Characteristics
Hepatic
- No history of documented hepatitis C
- No documented active hepatitis B
- Bilirubin no greater than 1.5 times upper limit of normal (ULN)
- ALT less than 2.5 times ULN
Renal
- Creatinine less than 1.5 times ULN
Cardiovascular
- No New York Heart Association class III or IV heart disease
- No clinical history or evidence of congestive heart failure
- No severe cardiac dysfunction
- LVEF greater than 35%
Pulmonary
- No prior or concurrent active or latent tuberculosis (TB)
- No evidence of prior or concurrent active TB (i.e., fibrotic or pleural
scarring, pulmonary nodules, mediastinal and/or hilar lymphadenopathy, upper
lobe volume loss, or cavitation) by chest x-ray
- Negative intradermal tuberculin skin test (i.e., induration less than 5 mm)
- No severe pulmonary dysfunction
Immunologic
- No prior or concurrent opportunistic infection (e.g., herpes zoster, cytomegalovirus,
Pneumocystic carinii, aspergillosis, histoplasmosis, or mycobacteria other than TB)
within the past 6 months
- No concurrent severe (CTC grade III or IV) active, chronic, or recurrent infections
- No recent history of allergies
- HIV negative
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 6 months after study
participation
- No prior clinically significant adverse event to murine or chimeric proteins or
human/murine recombinant products
- No recent contact with an individual with active TB
- No poor medical risk due to other systemic disease
- No multiple sclerosis or other demyelinating disorder
- No peripheral neuropathy greater than CTC grade 1
- No other malignancy within the past 5 years except adequately treated carcinoma in
situ of the cervix or nonmelanoma skin cancer
- No psychological, familial, sociological, or geographical condition that would
preclude study compliance
PRIOR CONCURRENT THERAPY:
Biologic therapy
- No prior infliximab or other monoclonal antibodies
- At least 6 weeks since prior hematopoietic growth factors for MDS
- At least 3 months since prior therapy targeted at reducing tumor necrosis factor
(TNF) alpha (e.g., pentoxifylline, thalidomide, or etanercept)
- No concurrent epoetin alfa, filgrastim (G-CSF), or sargramostim (GM-CSF)
- No other concurrent drugs targeted at reducing TNF alpha (e.g., pentoxifylline,
thalidomide, or etanercept)
Chemotherapy
- Not specified
Endocrine therapy
- Not specified
Radiotherapy
- Not specified
Surgery
- No prior solid organ transplantation
- Corneal transplantation more than 3 months ago allowed
Other
- No prior randomization to this clinical trial
- At least 6 weeks since prior treatment for MDS (except supportive care)
- No other concurrent investigational agents
- No other concurrent anticancer therapy
- No concurrent therapeutic-dose nonsteroidal anti-inflammatory drugs (NSAIDs)
- Concurrent sporadic (no more than 3 tablets/week) over-the-counter NSAIDs
allowed
- Concurrent cardioprotective doses (80 mg/day or equivalent) of aspirin allowed
