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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02663752
• Date of registration: 21/01/2016
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharmaceuticals
• Public title: A Phase II Pilot Study to Assess the Presence of Molecular Factors Predictive for Hematologic Response in Myelodysplastic Syndrome Patients Receiving Deferasirox Therapy. EXPHAR
• Scientific 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.
• Date of first enrolment: May 30, 2016
• Target sample size: 1
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT02663752
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Basic Science. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Belgium

Key inclusion & exclusion criteria

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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Myelodysplastic Syndrome

Intervention(s)

Procedure: Bone marrow aspirate

Drug: Deferasirox

Primary Outcome(s)

Fold Increase/Decrease in Gene Transcription From Baseline Bone Marrow Aspirate of Responders Versus Non-responders' [Time Frame: 18 months]

Secondary Outcome(s)

Changes in Transferrin Saturation Levels [Time Frame: Baseline, 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]

Time to Response [Time Frame: 18 months]

Secondary ID(s)

CICL670ABE04

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 05/07/2018
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02663752