- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02663752
A Phase II Pilot Study to Assess the Presence of Molecular Factors Predictive for Hematologic Response in Myelodysplastic Syndrome Patients Receiving Deferasirox Therapy. (EXPHAR)
A Phase II Pilot Study to Assess the Presence of Molecular Factors Predictive for Hematologic Response in Myelodysplastic Syndrome Patients Receiving Deferasirox Therapy in Hematological Centers in Belgium Using Gene Expressing Profiling From Baseline Bone Marrow.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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-
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Liege, Belgium, 4000
- Novartis Investigative Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Written informed consent obtained prior to any other study procedure,
- Males or females ≥ 18 years of age,
- MDS according to WHO criteria lasting ≥ 14 weeks at the time of screening, IPSS score <1.5 (low and intermediate-1 risk patients) at the time of screening using the IPSS score of 1997
- Treatment with deferasirox:
- Only for the responder group: Treatment with deferasirox for prevention or treatment of IOL for at least 14 weeks before screening.
- Only for the non-responder group: Treatment with deferasirox for at least 9 months for prevention or treatment of IOL before screening to exclude patients with a late hematological response.
- Only for responder-group: Patient with hematological response defined according to the IWG criteria of 2006 which must last at least 8 weeks, confirmed by the scientific advisory committee. In case a hematological response is identified retrospectively, the confirmation will be based on the last available blood result showing hematological response according to the IWG criteria of 2006. In this case, an archived bone marrow sample at the moment of response has to be available in order to be eligible. This archived bone marrow had to be taken at the moment when hematological response was present for at least 8 weeks and was still ongoing at the moment of sampling, according to the IWG criteria of 2006 in order to be eligible. When a bone marrow sample was taken after the hematological response had already disappeared, the sample is not eligible for further analysis.
- Only for non-responder group: confirmation by the scientific advisory committee that patient is eligible based on matched-pairing and confirmation of no hematological response. Minimal requirements for matched pairing include age, sex, IPSS score, hemoglobin level, transfusion need at baseline, treatment duration with deferasirox and time since MDS diagnosis. Pairing can be extended according to level of leukopenia, thrombocytopenia, serum ferritin level at baseline, comorbidities and transfusion history. More details about pairing are described in the protocol. In case a non-responder is identified retrospectively and an archival bone marrow is available at that documented time of non-response, this can be used for further analysis. In that case, an interval of 4 weeks between blood sampling for documentation of non-response and bone marrow sampling is allowed.
- Bone marrow aspirate/RNA taken at the time of MDS diagnosis (at baseline) retrievable from patient's hospital. This should be checked by the treating hematologist/oncologist before referring the patient for potential inclusion to the study. This aspirate/RNA has to be preserved under the right circumstances in order to ensure the quality of the RNA. The sample most be frozen viably, meaning controlled rate freezing and addition of a protector dimethyl sulfoxide DMSO and preserved in -80°C. Preservation of cells that are lysed in a lysis buffer upon arrival in the lab, and stored at -20°C until RNA-extraction are also useful for this study.
Exclusion Criteria:
- Known concomitant presence of anemia due to iron, B12 or folate deficiencies, auto-immune or hereditary hemolysis, gastro-intestinal bleeding or medication induced anemia at the time of screening,
- Known infection with viral hepatitis B (HBV) or viral hepatitis C (HCV) defined as the presence in blood of HBV antigens in absence of HB antibodies, or presence of HCV antibodies at the time of screening,
- Known history of positivity to human immunodeficiency virus (HIV) measured by enzyme-linked immunosorbent assay (ELISA) or western blot at the time of screening,
- Patient participating in another clinical trial or receiving any investigational drug at the time of screening within 1 month prior to study inclusion
- History of other malignancy within the last five years, with the exception of basal skin carcinoma or cervical carcinoma in situ or completely resected colonic polyps carcinoma in situ
- Concomitant treatment with other drugs known or suspected to elicit hematological response. (azacitidine, hematopoietic growth factors, granulocyte colony stimulating factors, valproate, lenalidomide, thalidomide, ATG, cyclosporine, arsenic trioxide).When patients are still receiving red blood cell transfusions, patients are still eligible for study inclusion as long as they meet the IWG criteria of 2006
- Female patients who are pregnant or breast feeding
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Other: Deferasirox
All patients are already on commercial deferasirox before entering the study.
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Patients experiencing a hematological response and patients not experiencing a hematological response while on deferasirox treatment received a new bone marrow aspirate in order to investigate the presence of differential gene expression between those two groups
Patients are already on commercial deferasirox before entering the study.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Fold Increase/Decrease in Gene Transcription From Baseline Bone Marrow Aspirate of Responders Versus Non-responders'
Time Frame: 18 months
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Using next-generation sequencing, gene expression profiling in responder and non-responder patients were to be performed on existing bone marrow aspirate samples.
Gene transcription were then to be compared between the two groups and the fold increase/decrease in differentially expressed genes were to be calculated.
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18 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to Response
Time Frame: 18 months
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The time to response is defined as the time (in months) between the date of deferasirox initiation and the date of the first documented hematological response only in the responder group.
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18 months
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Changes in Serum Ferritin Levels
Time Frame: Baseline, 18 months
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From baseline to time of response (responder group) or time to last follow up (non-responders)
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Baseline, 18 months
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Deferasirox Dose Used
Time Frame: 18 months
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Deferasirox dose is defined as the average daily dose (mg/kg/d) given to the patient from treatment initiation to the emergence of hematological response in the responder group or the time of enrollment in the study in the non-responder group.
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18 months
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Changes in Serum Transferrin Levels
Time Frame: Baseline, 18 months
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From baseline to time of response (responder group) or time to last follow up (non-responders)
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Baseline, 18 months
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Changes in Transferrin Saturation Levels
Time Frame: Baseline, 18 months
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From baseline to time of response (responder group) or time to last follow up (non-responders)
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Baseline, 18 months
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CICL670ABE04
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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