Myelodysplastic SyndromePhase 2EXPHARNCT02663752
A Phase II Pilot Study to Assess the Presence of Molecular Factors Predictive for Hematologic Response in Myelodysplastic Syndrome Patients Receiving Deferasirox Therapy.
A Phase 2 study testing Bone marrow aspirate and Deferasirox in people with Myelodysplastic Syndrome, run by Novartis Pharmaceuticals at 1 site in Belgium.
Trial summary
Several previous studies (clinical and non-clinical) hypothesize that treatment with deferasirox causes a hematological improvement in transfused patients with low and intermediate-1 risk myelodysplastic syndrome. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndrome
- What is being tested?
- Bone marrow aspirate and Deferasirox
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteBelgium
- Study dates
- 30 May 2016to 1 Jul 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Several previous studies (clinical and non-clinical) hypothesize that treatment with deferasirox causes a hematological improvement in transfused patients with low and intermediate-1 risk myelodysplastic syndrome. The purpose of this study was to assess the presence of genetic biomarkers predictive for hematologic response by the use of gene expression profiling of bone marrow aspirates obtained from MDS patients with or without hematological response.
Read the detailed description
This trial was terminated due to low enrollment.
- Conditions
- Myelodysplastic Syndrome
- Being tested
- Bone marrow aspirate, Deferasirox
- Keywords
- deferasirox, MDS, RNA expression, predictive biomarker
- Medical subject headings
- Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bone marrow aspirateProcedure or surgery
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
DeferasiroxDrug
Patients are already on commercial deferasirox before entering the study.
| Study group | Role | What they receive |
|---|---|---|
| Deferasirox | Other | All patients are already on commercial deferasirox before entering the study. Receives: Procedure: Bone marrow aspirate; Drug: Deferasirox |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fold Increase/Decrease in Gene Transcription From Baseline Bone Marrow Aspirate of Responders Versus Non-responders'
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.
Measured: 18 months
Secondary outcomes (5)
Time to Response
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.
Measured: 18 months
Changes in Serum Ferritin Levels
From baseline to time of response (responder group) or time to last follow up (non-responders)
Measured: Baseline, 18 months
Deferasirox Dose Used
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.
Measured: 18 months
Changes in Serum Transferrin Levels
From baseline to time of response (responder group) or time to last follow up (non-responders)
Measured: Baseline, 18 months
Changes in Transferrin Saturation Levels
From baseline to time of response (responder group) or time to last follow up (non-responders)
Measured: Baseline, 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2016 (estimated)
- Study start30 May 2016
- Primary completion1 Jul 2016
- Study completion1 Jul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Myelodysplastic SyndromeStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02663752
- Sponsor's protocol ID
- CICL670ABE04
- Acronym
- EXPHAR
- Status last verified
- Jul 2018
- First submitted
- 21 Jan 2016
- Last updated
- 23 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: 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
Study at a glance
From the registry record, last updated by the sponsor on 23 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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.
- ClinicalTrials.gov ID
- NCT02663752
- Acronym / sponsor ID
- EXPHAR / CICL670ABE04
- Conditions
- Myelodysplastic Syndrome
- Keywords
- deferasirox, MDS, RNA expression, predictive biomarker
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 30 May 2016 (actual)
- Primary completion
- 1 Jul 2016 (actual)
- Study completion
- 1 Jul 2016 (actual)
- First posted
- 26 Jan 2016 (estimated)
- Results
- Posted 5 Jul 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Several previous studies (clinical and non-clinical) hypothesize that treatment with deferasirox causes a hematological improvement in transfused patients with low and intermediate-1 risk myelodysplastic syndrome. The purpose of this study was to assess the presence of genetic biomarkers predictive for hematologic response by the use of gene expression profiling of bone marrow aspirates obtained from MDS patients with or without hematological response.
Detailed description
This trial was terminated due to low enrollment.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Deferasirox | Other | Procedure: Bone marrow aspirate, Drug: DeferasiroxAll patients are already on commercial deferasirox before entering the study. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bone marrow aspiratePatients 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 | Procedure or surgery | Deferasirox |
| DeferasiroxPatients are already on commercial deferasirox before entering the study. | Drug | Deferasirox |
Primary outcome
Fold Increase/Decrease in Gene Transcription From Baseline Bone Marrow Aspirate of Responders Versus Non-responders'
Time frame: 18 months
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.
5 secondary outcomes
Time to Response
Time frame: 18 months
Changes in Serum Ferritin Levels
Time frame: Baseline, 18 months
Deferasirox Dose Used
Time frame: 18 months
Changes in Serum Transferrin Levels
Time frame: Baseline, 18 months
Changes in Transferrin Saturation Levels
Time frame: Baseline, 18 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bone marrow aspirate and Deferasirox in people with Myelodysplastic Syndrome, run by Novartis Pharmaceuticals at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 23 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Jul 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fold Increase/Decrease in Gene Transcription From Baseline Bone Marrow Aspirate of Responders Versus Non-responders' (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Aug 2018.