Phase I Study of Vidaza and Velcade (Bortezomib) in Acute Myeloid Leukemia
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 23
- Locations
- 1
- Primary Endpoint
- Maximum tolerated dose of bortezomib in combination with azacytidine
Study Overview
Brief Summary
RATIONALE: Drugs used in chemotherapy, such as azacytidine work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking blood flow to the cancer and by blocking some of the enzymes needed for cell growth. Giving azacytidine together with bortezomib may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib when giving together with azacytidine in treating patients with relapsed or refractory acute myeloid leukemia or myelodysplastic syndromes.
Detailed Description
OBJECTIVES:
Primary
- To determine the maximum tolerated dose (MTD) bortezomib in combination with Azacytidine in patients with relapsed/refractory acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).
- To define the specific toxicities and the dose limiting toxicity (DLT) of Azacytidine plus bortezomib combination.
Secondary
- To determine the overall response rate (ORR).
- To determine the rate of complete remission (CR) of Azacytidine plus bortezomib in relapsed/refractory AML and MDS.
- To correlate the biological activity of Azacytidine as demethylating agent (changes in target gene methylation and gene expression, DNMT1 protein expression, global methylation) with clinical endpoints and plasma pharmacokinetics of azacytidine.
- To characterize the biological activity of bortezomib as a potential demethylating agent.
- To correlate intracellular concentration of azacytidine-triphosphate with global DNA methylation and other biological endpoints as well as clinical response.
- To explore the biologic role of microRNAs in determining clinical response to the azacytidine plus bortezomib combination and achievement of the other pharmacodynamic endpoints.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Vidaza and Velcade
Vidaza 75mg/m2 IV over 30 min daily on days 1-7 This dose is the same for all dose levels. Velcade will be given immediately after Vidaza is completed at one of the following dose levels: 1, 2, 3, 4
Intervention: Vidaza (Drug)
Vidaza and Velcade
Vidaza 75mg/m2 IV over 30 min daily on days 1-7 This dose is the same for all dose levels. Velcade will be given immediately after Vidaza is completed at one of the following dose levels: 1, 2, 3, 4
Intervention: Velcade (Drug)
Outcomes
Primary Outcomes
Maximum tolerated dose of bortezomib in combination with azacytidine
Time Frame: Up to 1 year
Determine the maximum tolerated dose (MTD) of Velcade (bortezomib, PS-341) in combination with Vidaza in patients with relapsed/refractory acute myeloid leukemia (AML) and Myelodysplastic Syndrome (MDS)
Overall response rate
Time Frame: Up to 1 year
Determine the overall response rate (ORR)
Secondary Outcomes
- Correlation of intracellular concentration of azacytidine-triphosphate with global DNA methylation and other biological endpoints as well as clinical response(Up to 1 year)
- Rate of complete remission(Up to 1 year)
- Biological activity of azacytidine and bortezomib as demethylating agents(Up to 1 year)
- Achievement of other pharmacodynamic endpoints(Up to 1 year)
- Biologic role of microRNAs in determining clinical response to study drugs(Up to 1 year)