Infliximab in Treating Patients With Myelodysplastic Syndrome

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies, such as infliximab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. PURPOSE: Randomized phase II trial to study the effectiveness of infliximab in treating patients who have myelodysplastic syndrome.

Detailed Description
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OBJECTIVES: Determine the therapeutic activity of 2 different doses of infliximab on peripheral blood cell count and peripheral and bone marrow blast cell count in patients with low- or intermediate-risk myelodysplastic syndromes. Determine the subjective and objective toxicity of these regimens in these patients. Determine the response rates (complete and partial response and hematological improvement) in patients treated with these regimens. Determine the duration of response in patients treated with these regimens. OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to cytogenetics (good vs intermediate vs unknown due to failure), overall International Prognostic Scoring System score (low [0] vs intermediate 1 [0.5-1.0] vs intermediate 2 [1.5-2.0]), and participating center. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive infliximab IV on days 1, 15, 43, 71, 99, 127, 155, and 183 in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive a higher dose of infliximab as in arm I. Patients achieving response (complete or partial response or hematological improvement) continue therapy beyond day 183 in the absence of disease progression. Patients are followed at 2 weeks and then every 3 months thereafter. PROJECTED ACCRUAL: A total of 80 patients (40 per treatment arm) will be accrued for this study within 2 years.

Official Title
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Randomized Phase II Trial With Infliximab (Remicade) in Patients With Myelodysplastic Syndrome and a Relatively Low Risk of Developing Acute Leukemia

Conditions
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Myelodysplastic Syndromes

Intervention / Treatment
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* Biological: infliximab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: infliximab|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best response as measured by Cheson response criteria |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of highest grade toxicity as assessed by CTCAE v3.0 after response |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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refractory anemia with excess blasts, refractory anemia with ringed sideroblasts, refractory anemia, de novo myelodysplastic syndromes, secondary myelodysplastic syndromes, previously treated myelodysplastic syndromes