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

NCT02663752 | Terminated Phase 2 Results DMC

• 1 other identifier: CICL670ABE04
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Myelodysplastic Syndrome

Keywords

deferasirox; MDS; RNA expression; predictive biomarker

Outcome Measures

Primary Outcomes (1)

• 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.

  18 months

Secondary Outcomes (5)

• Time to Response

  18 months

• Changes in Serum Ferritin Levels

  Baseline, 18 months

• Deferasirox Dose Used

  18 months

• Changes in Serum Transferrin Levels

  Baseline, 18 months

• Changes in Transferrin Saturation Levels

  Baseline, 18 months

Study Arms (1)

Deferasirox

OTHER

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

Procedure: Bone marrow aspirate; Drug: Deferasirox

Interventions

Bone marrow aspirate PROCEDURE

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

Deferasirox

Deferasirox DRUG

Patients are already on commercial deferasirox before entering the study.

Deferasirox

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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,
• 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
• Female patients who are pregnant or breast feeding

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (1)

Novartis Investigative Site

Liège, 4000, Belgium

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Deferasirox

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

The trial was terminated due to low enrollment.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2016
• First Posted: January 26, 2016
• Study Start: May 30, 2016
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: August 23, 2018
• Results First Posted: July 5, 2018

Record last verified: 2018-07

Locations

BE (1)