Bortezomib and Low Dose Cytarabine in the Treatment of High-risk Myelodysplastic Syndromes

Phase 1

Completed

• Conditions: Myelodysplastic Syndromes

• Registration Number: NCT00411905
• Lead Sponsor: Groupe Francophone des Myelodysplasies

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

Bone marrow aspirates are evaluated just before the first cycle, after the second and after the fourth cycles

Responding patients may continue the treatment for 2 further cycles

Study Timeline

• Study Start: 2006-06-01
• Study First Submitted: 2006-12-14
• Study First Submitted QC: 2006-12-14
• Study First Posted: 2006-12-15
• Status Verified: 2010-07
• Primary Completion: 2010-07-08
• Study Completion: 2011-08-01
• Last Update Submitted: 2025-01-06
• Last Update Posted: 2025-01-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 45

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
• LMMC
• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Efficacy and safety evaluation	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
Partial Response

Secondary Outcome Measures

Name	Time	Method
Hematological Improvement

Trial Locations

Locations (15)

CHU Angers; 🇫🇷 Angers, France

Hopital Avicenne; 🇫🇷 Bobigny, France

Institut Bergonie; 🇫🇷 Bordeaux, France

CHU de Caen; 🇫🇷 Caen, France

CHU Dijon; 🇫🇷 Dijon, France

CHU Albert Michallon; 🇫🇷 Grenoble, France

CHU de Limoges; 🇫🇷 Limoges, France

Hopital Paoli Calmette; 🇫🇷 Marseille, France

CHU Archet; 🇫🇷 Nice, France

Hopital Cochin; 🇫🇷 Paris, France

Centre Hospitalier Joffre; 🇫🇷 Perpignan, France

Centre Henry Becquerel; 🇫🇷 Rouen, France

Centre Hospitalier Universitaire de STRASBOURG; 🇫🇷 Strasbourg, France

CHU Purpan; 🇫🇷 Toulouse, France

CHU Brabois; 🇫🇷 Vandoeuvre, France