Velcade in Myelodysplastic Syndrome - Pilot Study
Primary Purpose
MDS
Status
Terminated
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Velcade
Sponsored by
About this trial
This is an interventional treatment trial for MDS focused on measuring MDS, Velcade
Eligibility Criteria
Inclusion Criteria:
- Patients aged 18 -75 years.
Patients with the following clinical diagnosis: RA(FAB) or RCMD (WHO), RARS (FAB) or RCDM-RS(WHO), RAEB (FAB) or RAEB I (WHO), RAEB II (WHO), and:
- IPSS intermediate-2 (score 1.5-2) or high (score 2.5-3) not previously treated with chemotherapy (CT) and not eligible for intensive chemotherapy or allogeneic stem cell transplantation (SCT), or
- IPSS intermediate-1(score 0.5-1) or low (score 0), EPO or immunosuppressive (Cyclosporine, CSA; anti-tymocyte globulin, ATG) therapies resistant or not eligible for these therapies, and transfusion dependent.
- Patients willing and able to comply with the protocol requirements.
- Patients given voluntary written informed consent to participate in the study, with the understanding that consent may be withdrawn at any time without prejudice to future medical care.
- Male and female patients willing to use acceptable methods for contraception, for the duration of the study.
- Patients with WHO performance Status (PS) 0-2, and life expectancy > 3 months.
- Renal function tests ≤ 2 x upper limit of normal values.
- AST/GOT, ALT/GPT ≤ 2.5 x upper limit of normal values.
- Total bilirubine ≤ 1.5 x upper limit of normal value.
Exclusion Criteria:
- Patient has Grade 2 (as defined by the NCI Common Toxicity Criteria-CTC) peripheral neuropathy within 14 days before enrollment.
- Patient has hypersensitivity to bortezomib, boron or mannitol.
- Patient has received prior treatment with bortezomib
- Patient is pregnant or nursing
- Patient has received other investigational drugs within 14 days before enrollment
- Patient has received prior chemotherapy
- Patient had a major surgery within 4 weeks before enrollment
- Patient had myocardial infarction within 6 months of enrollment or has class III-IV heart failure, uncontrolled angina or arrhythmias
- Patient has been treated for previous malignancy within 5 years before enrollment
- Patient has uncontrolled hypertension or diabetes mellitus
- Patient is known to have HBV or HCV active hepatitis or is human immunodeficiency virus (HIV)-positive
- Patient has systemic infections requiring treatment
Sites / Locations
- Centro Oncologico Basilicata
- Istituto di Ematologia e Oncologia Medica L. e A. Seragnoli
- Ospedale Niguarda "Ca Grande"
- A.O Umberto I
Outcomes
Primary Outcome Measures
to determine activity of Velcade in patients with MDS, intermediate-2 or high risk, and intermediate-1 or low risk unresponsive or not eligible for treatment with erythropoietin or immunosuppressive agents as assessed according to response criteria.
Secondary Outcome Measures
to determine whether Velcade prolongs time to progression and/or survival; safety and tolerability as assessed by incidence of clinical and laboratory toxicities; quality of life in relation to neurotoxicity.
Full Information
NCT ID
NCT00440076
First Posted
February 23, 2007
Last Updated
April 21, 2015
Sponsor
Gruppo Italiano Malattie EMatologiche dell'Adulto
1. Study Identification
Unique Protocol Identification Number
NCT00440076
Brief Title
Velcade in Myelodysplastic Syndrome - Pilot Study
Official Title
Phase II Study of PS341 (VELCADE) in Myelodysplastic Syndromes (MDS). EudraCT Number 2004-002935-23
Study Type
Interventional
2. Study Status
Record Verification Date
April 2015
Overall Recruitment Status
Terminated
Why Stopped
Low accrual
Study Start Date
August 2006 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
March 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gruppo Italiano Malattie EMatologiche dell'Adulto
4. Oversight
5. Study Description
Brief Summary
This is a four-center open-label study designed to determine activity of Velcade in Myelodysplastic Syndrome (MDS) patients. A total of 28 subjects will be enrolled. The patients will be registered to GIMEMA Data Center before therapy starts and after inclusion criteria verification.
Detailed Description
The Myelodysplastic Syndromes (MDS) are an heterogeneous group of clonal disorders of the hematopoietic stem cell characterized by ineffective hematopoiesis leading to peripheral cytopenias, and variable risk of progression to more advanced disease and/or transformation to acute myeloid leukemia (AML). The disease affects predominantly elderly individuals (median age 69 years); the overall incidence is about 4 per 100,000 individuals but this rises to > 30 per 100,000 in the over 70 year age population.
Therapy for MDS has included hematopoietic growth factors (in primis EPO, in combination or not with granulocyte-colony stimulating factor- G-CSF or granulocyte-colony stimulating factor-GM-CSF), differentiating agents, immunotherapy, low dose chemotherapy strategies, AML-like induction regimens, traditional cytotoxic agents, and hematopoietic stem cell transplantation (HSCT) strategies. With the exception of HSCT, which can result in long-term survival in 23% to 50% of patients (Ref. 10) therapy for MDS has not consistently shown a survival advantage, and also modest results have been obtained in an attempt to improve anemia and/or the other cytopenias, and to decrease the number of red blood cell (RBC) transfusions. Furthermore, MDS is primarily a disease of older patients who cannot tolerate aggressive therapy and therefore cannot receive HSCT.
No therapy has thus been considered standard for MDS, and supportive therapy, including RBC transfusions, platelet transfusions and antibiotic therapy has often been focus of care, especially in the older patient population.
VELCADE™ (bortezomib) for injection is a small molecule proteasome inhibitor developed by Millennium Pharmaceuticals, Inc., (MPI) as a novel agent to treat human malignancies. VELCADE is currently approved by the US FDA for the treatment of multiple myeloma patients who have received at least 2 prior therapies and have demonstrated disease progression on the last therapy. VELCADE is a modified dipeptidyl boronic acid derived from leucine and phenylalanine; its chemical name is N pyrazinecarbonyl L phenylalanine L leucine boronic acid and has a molecular weight of 384.25 daltons.
Data from non clinical and clinical studies conducted to date support the development of Velcade for the treatment of human malignancies.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
MDS
Keywords
MDS, Velcade
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
28 (Actual)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
Velcade
Primary Outcome Measure Information:
Title
to determine activity of Velcade in patients with MDS, intermediate-2 or high risk, and intermediate-1 or low risk unresponsive or not eligible for treatment with erythropoietin or immunosuppressive agents as assessed according to response criteria.
Secondary Outcome Measure Information:
Title
to determine whether Velcade prolongs time to progression and/or survival; safety and tolerability as assessed by incidence of clinical and laboratory toxicities; quality of life in relation to neurotoxicity.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients aged 18 -75 years.
Patients with the following clinical diagnosis: RA(FAB) or RCMD (WHO), RARS (FAB) or RCDM-RS(WHO), RAEB (FAB) or RAEB I (WHO), RAEB II (WHO), and:
IPSS intermediate-2 (score 1.5-2) or high (score 2.5-3) not previously treated with chemotherapy (CT) and not eligible for intensive chemotherapy or allogeneic stem cell transplantation (SCT), or
IPSS intermediate-1(score 0.5-1) or low (score 0), EPO or immunosuppressive (Cyclosporine, CSA; anti-tymocyte globulin, ATG) therapies resistant or not eligible for these therapies, and transfusion dependent.
Patients willing and able to comply with the protocol requirements.
Patients given voluntary written informed consent to participate in the study, with the understanding that consent may be withdrawn at any time without prejudice to future medical care.
Male and female patients willing to use acceptable methods for contraception, for the duration of the study.
Patients with WHO performance Status (PS) 0-2, and life expectancy > 3 months.
Renal function tests ≤ 2 x upper limit of normal values.
AST/GOT, ALT/GPT ≤ 2.5 x upper limit of normal values.
Total bilirubine ≤ 1.5 x upper limit of normal value.
Exclusion Criteria:
Patient has Grade 2 (as defined by the NCI Common Toxicity Criteria-CTC) peripheral neuropathy within 14 days before enrollment.
Patient has hypersensitivity to bortezomib, boron or mannitol.
Patient has received prior treatment with bortezomib
Patient is pregnant or nursing
Patient has received other investigational drugs within 14 days before enrollment
Patient has received prior chemotherapy
Patient had a major surgery within 4 weeks before enrollment
Patient had myocardial infarction within 6 months of enrollment or has class III-IV heart failure, uncontrolled angina or arrhythmias
Patient has been treated for previous malignancy within 5 years before enrollment
Patient has uncontrolled hypertension or diabetes mellitus
Patient is known to have HBV or HCV active hepatitis or is human immunodeficiency virus (HIV)-positive
Patient has systemic infections requiring treatment
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Giuliana ALIMENA, MD, PHD
Organizational Affiliation
Università degli Studi di Roma "La Sapienza", Dipartimento di Biotecnologie Cellulari ed Ematolgia
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centro Oncologico Basilicata
City
Rionero in Vulture
State/Province
Potenza
Country
Italy
Facility Name
Istituto di Ematologia e Oncologia Medica L. e A. Seragnoli
City
Bologna
Country
Italy
Facility Name
Ospedale Niguarda "Ca Grande"
City
Milano
Country
Italy
Facility Name
A.O Umberto I
City
Roma
Country
Italy
12. IPD Sharing Statement
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Velcade in Myelodysplastic Syndrome - Pilot Study
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