EXPHAR: A Phase II Pilot Study to Assess the Presence of Molecular Factors Predictive for Hematologic Response in Myelodysplastic Syndrome Patients Receiving Deferasirox Therapy.

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Terminated
CT.gov ID
NCT02663752
Collaborator
(none)
1
Enrollment
1
Location
1
Arm
1.1
Actual Duration (Months)
1
Patients Per Site Per Month

Study Details

Study Description

Brief 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. 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.

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

Detailed Description

This trial was terminated due to low enrollment.

Study Design

Study Type:
Interventional
Actual Enrollment :
1 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Basic Science
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.
Actual Study Start Date :
May 30, 2016
Actual Primary Completion Date :
Jul 1, 2016
Actual Study Completion Date :
Jul 1, 2016

Arms and Interventions

ArmIntervention/Treatment
Other: Deferasirox

All patients are already on commercial deferasirox before entering the study.

Procedure: Bone marrow aspirate
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

Drug: Deferasirox
Patients are already on commercial deferasirox before entering the study.

Outcome Measures

Primary Outcome Measures

  1. Fold Increase/Decrease in Gene Transcription From Baseline Bone Marrow Aspirate of Responders Versus Non-responders' [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.

Secondary Outcome Measures

  1. Time to Response [18 months]

    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.

  2. Changes in Serum Ferritin Levels [Baseline, 18 months]

    From baseline to time of response (responder group) or time to last follow up (non-responders)

  3. Deferasirox Dose Used [18 months]

    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.

  4. Changes in Serum Transferrin Levels [Baseline, 18 months]

    From baseline to time of response (responder group) or time to last follow up (non-responders)

  5. Changes in Transferrin Saturation Levels [Baseline, 18 months]

    From baseline to time of response (responder group) or time to last follow up (non-responders)

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1Novartis Investigative SiteLiegeBelgium4000

Sponsors and Collaborators

  • Novartis Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02663752
Other Study ID Numbers:
  • CICL670ABE04
First Posted:
Jan 26, 2016
Last Update Posted:
Aug 23, 2018
Last Verified:
Jul 1, 2018
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Novartis Pharmaceuticals
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment DetailsStudy has been discontinued because of low patient recruitment.
Pre-assignment Detail
Arm/Group TitleDeferasirox
Arm/Group DescriptionAll patients are already on commercial deferasirox before entering the study.
Period Title: Overall Study
STARTED1
COMPLETED1
NOT COMPLETED0

Baseline Characteristics

Arm/Group TitleDeferasirox
Arm/Group DescriptionAll patients are already on commercial deferasirox before entering the study.
Overall Participants0
Age, Customized (years) []
Sex/Gender, Customized (number) []

Outcome Measures

1. Primary Outcome
TitleFold Increase/Decrease in Gene Transcription From Baseline Bone Marrow Aspirate of Responders Versus Non-responders'
DescriptionUsing 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.
Time Frame18 months

Outcome Measure Data

Analysis Population Description
There was no treatment administration specific to this study. The trial was terminated due to low enrollment. Because of the limited number of data collected an efficacy analysis was not possible.
Arm/Group TitleDeferasirox
Arm/Group DescriptionAll patients are already on commercial deferasirox before entering the study.
Measure Participants0
2. Secondary Outcome
TitleTime to Response
DescriptionThe 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.
Time Frame18 months

Outcome Measure Data

Analysis Population Description
There was no treatment administration specific to this study. The trial was terminated due to low enrollment. Because of the limited number of data collected an efficacy analysis was not possible.
Arm/Group TitleDeferasirox
Arm/Group DescriptionAll patients are already on commercial deferasirox before entering the study.
Measure Participants0
3. Secondary Outcome
TitleChanges in Serum Ferritin Levels
DescriptionFrom baseline to time of response (responder group) or time to last follow up (non-responders)
Time FrameBaseline, 18 months

Outcome Measure Data

Analysis Population Description
There was no treatment administration specific to this study. The trial was terminated due to low enrollment. Because of the limited number of data collected an efficacy analysis was not possible.
Arm/Group TitleDeferasirox
Arm/Group DescriptionAll patients are already on commercial deferasirox before entering the study.
Measure Participants0
4. Secondary Outcome
TitleDeferasirox Dose Used
DescriptionDeferasirox 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.
Time Frame18 months

Outcome Measure Data

Analysis Population Description
There was no treatment administration specific to this study. The trial was terminated due to low enrollment. Because of the limited number of data collected an efficacy analysis was not possible.
Arm/Group TitleDeferasirox
Arm/Group DescriptionAll patients are already on commercial deferasirox before entering the study.
Measure Participants0
5. Secondary Outcome
TitleChanges in Serum Transferrin Levels
DescriptionFrom baseline to time of response (responder group) or time to last follow up (non-responders)
Time FrameBaseline, 18 months

Outcome Measure Data

Analysis Population Description
There was no treatment administration specific to this study. The trial was terminated due to low enrollment. Because of the limited number of data collected an efficacy analysis was not possible.
Arm/Group TitleDeferasirox
Arm/Group DescriptionAll patients are already on commercial deferasirox before entering the study.
Measure Participants0
6. Secondary Outcome
TitleChanges in Transferrin Saturation Levels
DescriptionFrom baseline to time of response (responder group) or time to last follow up (non-responders)
Time FrameBaseline, 18 months

Outcome Measure Data

Analysis Population Description
There was no treatment administration specific to this study. The trial was terminated due to low enrollment. Because of the limited number of data collected an efficacy analysis was not possible.
Arm/Group TitleDeferasirox
Arm/Group DescriptionAll patients are already on commercial deferasirox before entering the study.
Measure Participants0

Adverse Events

Time FrameAdverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
Adverse Event Reporting Description There was no treatment administration specific to this study. The trial was terminated due to low enrollment. The patient did not experience any Adverse Events during the trial.
Arm/Group TitleDeferasirox
Arm/Group DescriptionAll patients are already on commercial deferasirox before entering the study.
All Cause Mortality
Deferasirox
Affected / at Risk (%)# Events
Total0/1 (0%)
Serious Adverse Events
Deferasirox
Affected / at Risk (%)# Events
Total0/1 (0%)
Other (Not Including Serious) Adverse Events
Deferasirox
Affected / at Risk (%)# Events
Total0/1 (0%)

Limitations/Caveats

The trial was terminated due to low enrollment.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data form all sites) in the clinical trial.

Results Point of Contact

Name/TitleStudy Director
OrganizationNovartis Pharmaceuticals
Phone862-778-8300
EmailNovartis.email@novartis.com
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02663752
Other Study ID Numbers:
  • CICL670ABE04
First Posted:
Jan 26, 2016
Last Update Posted:
Aug 23, 2018
Last Verified:
Jul 1, 2018