Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Azacitidine and Lintuzumab in Treating Patients With Previously Untreated Myelodysplastic Syndromes

Basic Trial Information

Objectives

Primary

1. To determine the complete response rate of the combination of lintuzumab and azacitidine in patients with myelodysplastic syndromes.

Secondary

1. To define the specific toxicities of this regimen.
2. To determine the overall response rate.
3. To determine the relationship between pretreatment expression of Syk and clinical response.
4. To determine whether the investigational agents modulate Syk expression and to correlate drug-induced changes in Syk with response to treatment.
5. To provide preliminary data on the biological activity of azacitidine as a demethylating agent (changes in target gene methylation and gene expression, DNMT1 protein expression, global methylation).
6. To perform exploratory studies of azacitidine-triphosphate with global DNA methylation.
7. To explore the biologic role of microRNA in determining clinical response to this regimen and achievement of the other pharmacodynamic endpoints.

Entry Criteria

Disease Characteristics:

• Diagnosis of myelodysplastic syndromes (MDS) by FAB or WHO criteria (FAB criteria for MDS includes ≤ 29% blasts and chronic myelomonocytic leukemia)
  • Previously untreated disease
    • Patients who have initiated azacytidine (1 course only) are eligible provided that the second course will begin on study within 5 weeks from the initiation of the first course
    • Prior cytokine therapy allowed
• Patients with therapy-related MDS are eligible
• No granulocytic sarcoma as the sole site of disease
• Patients with refractory anemia or refractory anemia with ringed sideroblasts must have significant marrow dysfunction as defined by meeting 1 of the following criteria:
  • Symptomatic anemia requiring RBC transfusions for ≥ 3 months
  • Platelet count < 50,000/mm³ on 2 occasions or clinically significant hemorrhage requiring transfusion
  • Neutrophil count < 1,000/mm³
  • No infection requiring IV antibiotics
• CD33 expression required on ≥ 25% of left-shifted dysplastic myeloid cells, including blasts
  • Testing will be done on bone marrow aspirate (testing on peripheral blood is allowed for patients whose CD33 expression in this cellular compartment cannot be ascertained)
• No active CNS disease

Prior/Concurrent Therapy:

• See Disease Characteristics
• No prior lenalidomide or thalidomide
• More than 6 months since prior chemotherapy or radiotherapy (for other cancers)
• More than 1 month since prior and no other concurrent investigational agents
• No concurrent ongoing therapeutic anticoagulation with warfarin, Lovenox, or similar agent
  • Low-dose prophylaxis therapy allowed
• No concurrent ongoing clopidogrel therapy
  • Patients who were using clopidogrel at screening and subsequently discontinued use due to ongoing or future risk of dug- and treatment-related cytopenias are eligible
• No other concurrent anticancer agents or therapies

Patient Characteristics:

• See Disease Characteristics
• Life expectancy attributed to a co-morbid medical illness > 6 months (if applicable)
• ECOG performance status 0-2
• Platelet count ≥ 10,000/mm³ with transfusion
• Total bilirubin < 2.0 mg/dL
• AST/ALT < 2.5 times upper limit of normal
• Creatinine < 2.0 mg/dL
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception before and during study treatment
• No uncontrolled concurrent illness including, but not limited to, any of the following:
  • NYHA class III-IV congestive heart failure
  • Unstable angina pectoris
  • Serious cardiac or ventricular arrhythmia
  • Uncontrolled active infection
  • Myocardial infarction within the past 6 months
  • Electrocardiographic evidence of acute ischemia or active conduction system abnormalities
  • Serious medical or psychiatric illness or social situations that are likely to interfere with participation in this study
• No baseline fibrinogen < 100 mg/dL or clinically significant disseminated intravascular coagulation
• More than 3 years since prior diagnosis or treatment of another malignancy except for any of the following:
  • Basal cell carcinoma or squamous cell carcinoma of the skin
  • In situ malignancy
  • Low-risk prostate cancer
• No HIV positivity requiring combination antiretroviral therapy
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to azacitidine or lintuzumab that are not easily managed
• No hypersensitivity to mannitol

Expected Enrollment

Outcomes

Complete response rate

Overall response rate

Outline

Patients receive azacitidine IV or subcutaneously once daily on days 1-7 and lintuzumab IV on days 2, 7, 15, and 22 (days 2 and 15 of course 1 only). Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Treatment modifications may apply according to response.

Blood and bone marrow samples are collected periodically for pharmacodynamic studies.

After completion of study treatment, patients are followed up for 5 years.

Trial Contact Information

Trial Lead Organizations

Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center

Alison Walker, MD, Principal investigator		Ph: 614-293-3196

Registry Information
Official Title		Phase II study of 5-azacytidine and lintuzumab in myelodysplastic syndromes (MDS)
Trial Start Date		2009-11-09 (estimated)
Trial Completion Date		2014-11-09 (estimated)
Registered in ClinicalTrials.gov		NCT00997243
Date Submitted to PDQ		2009-10-12
Information Last Verified		2009-10-15
NCI Grant/Contract Number		CA16058

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