Azacitidine and Lintuzumab in Treating Patients With Previously Untreated Myelodysplastic Syndromes
RATIONALE: Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as lintuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving chemotherapy together with monoclonal antibodies may be a better way to block cancer growth.
PURPOSE: This phase II trial is studying the side effects and how well giving azacitidine together with lintuzumab works in treating patients with previously untreated myelodysplastic syndromes.
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of 5-azacytidine and Lintuzumab in Myelodysplastic Syndromes (MDS)|
- Complete Response Rate [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]Response to therapy was determined based on percentage of blasts in bone marrow, hematopoiesis, and requirement for supportive care (i.e., transfusions or cytokine growth factors). The modified International Working Group response criteria was used, based on Cheson, et al.
- Overall Response Rate [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]Response to therapy was determined based on percentage of blasts in bone marrow, hematopoiesis, and requirement for supportive care (i.e., transfusions or cytokine growth factors). The modified International Working Group response criteria was used, based on Cheson, et al.
- Toxicities of the Combination [ Time Frame: up to 5 years ] [ Designated as safety issue: Yes ]All patients who received study drug were closely monitored for adverse events (AEs). All AEs that occured during study period were reported and the investigator determined the severity and relationship to study drug (unrelated, unlikely, possibly, probably, or definitely related). The NCI's CTCAE(Common Toxicity Criteria for Adverse Effects)v3.0 was used for grading AEs.
- Determine the Relationship Between Pretreatment Expression of Syk and Clinical Response; to Determine Whether the Investigational Agents Modulate Syk Expression and Correlate Drug-induced Changes in Syk With Response to Treatment [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
- Provide Preliminary Data on the Biological Activity of AZA as a Demethylating Agent (Changes in Target Gene Methylation and Gene Expression, DNMT1[Deoxyribonucleic Acid Methyltransferase 1 DNA Methyltransferase 1]Protein Expression, Global Methylation) [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
- Perform Exploratory Studies of AZA-triphosphate With Global DNA Methylation [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
- Explore the Biologic Role of microRNAs in Determining Clinical Response to the AZA Plus Lintuzumab Combination and Achievement of the Other Pharmacodynamic Endpoints [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
|Study Start Date:||November 2009|
|Study Completion Date:||May 2011|
|Primary Completion Date:||September 2010 (Final data collection date for primary outcome measure)|
Experimental: 5-azacytidine and Lintuzumab
Cycle 1- 5-azacytidine (Vidaza, AZA) 75mg/m2 IV/SC(subcutaneous)daily on days 1-7.
Subsequent Cycles (cycles to be repeated every 28 days) AZA 75mg/m2 IV/SC daily on days 1-7.
Cycle 1 600mg as an IV infusion (flat dose for all), given on days 2, 7, 15, and 22. Subsequent Cycles (cycles to be repeated every 28 days) 600mg as an IV infusion, given every other week, twice during each cycle, including one dose given during AZA therapy. Doses should be given at least 12 days apart. By convention, dosing on days 7 and 22 of each cycle will be encouraged, but due to expected issues of patient convenience (time, travel, etc.), the study requirements are every other week, twice during each cycle, with one dose during AZA treatment.
Other Name: SGN-33Drug: 5-azacytidine
75mg/m2 IV/SC daily on days 1-7.
- To determine the complete response rate of the combination of lintuzumab and azacitidine in patients with myelodysplastic syndromes.
- To define the specific toxicities of this regimen.
- To determine the overall response rate.
- To determine the relationship between pretreatment expression of Syk and clinical response.
- To determine whether the investigational agents modulate Syk expression and to correlate drug-induced changes in Syk with response to treatment.
- 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).
- To perform exploratory studies of azacitidine-triphosphate with global DNA methylation.
- To explore the biologic role of microRNA in determining clinical response to this regimen and achievement of the other pharmacodynamic endpoints.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00997243
|United States, Ohio|
|Ohio State University Medical Center|
|Columbus, Ohio, United States, 43210|
|Principal Investigator:||Alison Walker, MD||Ohio State University Comprehensive Cancer Center|