Phase I/II Study of Bortezomib and Low Dose Cytarabine in the Treatment of High-risk Myelodysplastic Syndromes
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 45
- Locations
- 15
- Primary Endpoint
- Partial Response
Study Overview
Brief Summary
We are evaluating the efficacy of the association of Low dose Cytarabine in association with Bortezomib in the treatment of patients diagnosed with high risk Myelodysplastic syndromes. Our aim is to decrease transfusion requirements and if possible induce a complete or at least a partial remission.
Detailed Description
Four cycles of treatment are proposed at 28 day intervals in an ambulatory setting
Cycle 1 :
- Cytarabine 10 mg /m2/day subcutaneous injection for 14 days
- Bortézomib 1,5mg/m2 days 1,4,8,11
Cycles 2, 3, 4 :
- Cytarabine 20 mg /m2/j subcutaneous injections for 14 days
- Bortézomib 1,5mg/m2 days 1,4,8,11
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
- •MDS with IPSS scores Int-2 or High
- •Life expectancy greater than 6 months
- •No other available treatment options
Exclusion Criteria
- •MDS with IPSS scores Low or Int-1
- •> 30% bone marrow blasts
- •clinical neuropathy of greater than grade 2
- •ECOG Score 3 or 4
- •Creatinine clearance of < 30 ml/min
- •Pregnant patients or lactating mothers
- •Patients having received intensive chemotherapy in the 3 months prior to inclusion
- •Patients with uncontrolled pulmonary, cardiac, neurological, gastro-intestinal or genito-urinary disorders
Outcomes
Primary Outcomes
Partial Response
Efficacy and safety evaluation
Time Frame: 18 mois
A total of 138 cycles were administered. The median number of cycles administered was 3·2 (range 0·5-8). Thirty-six patients (84%) received at least two cycles and 17 (40%) received the planned four cycles, six responding patients received 1-4 additional cycles. Treatment was dis- continued in the responding patients at progression to AML or for toxicity. The most common treatment-related adverse events were related to myelosuppression . Neutropenia (Grade 4) and thrombocytopenia (Grade 4) were seen during treatment in 51% and 46% of the patients, respectively. Three of the patients with pre-treatment Grade 0-2 neutropenia and thrombocytopenia developed Grade 3-4 toxicity complicated by infection and bleeding. Grade 3-4 neutropenia was responsible for infection in six patients. Grade 3-4
Complete Response
Secondary Outcomes
- Hematological Improvement