- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02038816
Azacitidine Plus Deferasirox (ICL670) in Higher Risk Myelodysplastic Syndromes (MDS)
April 24, 2018 updated by: Sunnybrook Health Sciences Centre
A PHASE II STUDY OF Azacitidine Plus Deferasirox (ICL670) in Higher Risk Myelodysplastic Syndromes (MDS)
Myelodysplastic syndromes are common blood disorders that can affect as many as one in 1000 Canadians over the age of 65.
They are characterized by low blood counts that require frequent blood transfusions.
The development of iron overload in these patients is inevitable.
The iron deposits in vital organs such as the heart and the liver and can lead to organ dysfunction.
Deferasirox is a well-studied drug that helps remove iron from the body.
Most people with this disorder die due to progression of their disease to acute leukemia through multiple mechanisms.
Iron overload in patients with myelodysplastic syndromes has been shown to be associated with shorter survival, and potentially a higher chance of leukemia.
In a certain sub-group of higher risk patients, the drug azacitidine has been shown to decrease the chance of progression to leukemia and death from it.
Thus, it is presently the standard of care for these patients.
However, 50% of higher risk patients are still unresponsive to this medication, leaving a large group of patients for which other treatment options are emergently needed.
Given that a large proportion of higher risk MDS patients fail to respond to azacitidine, and the evidence that iron deposition may lead to increased leukemic transformation, we would like to study whether iron removal from the body with deferasirox potentiates azacitidine in its effects on overall survival, as well as the chance of leukemia transformation.
This question needs to be addressed in a randomized controlled trial, and the first step is a preliminary study to determine if the combination of azacitidine and deferasirox has any biologic effect.
This study will determine whether this combination leads to blood count improvement over azacitidine alone.
If this drug combination ultimately proves more useful than azacitidine alone with respect to survival, this has the potential to impact the care of a large proportion of patients with myelodysplastic syndromes.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
Detailed Description
Patients with stable disease after 6 cycles of AZA with higher risk MDS will be randomized to either standard of care (continued AZA until progression ) or AZA + defasirox.
Primary endpoint is augmented response rate by the addition of deferasirox
Study Type
Interventional
Enrollment (Actual)
1
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Ontario
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Toronto, Ontario, Canada, M4N 3M5
- Odette Cancer Centre, Sunnybrook Health Sciences Centre
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Adults >18 yrs of age
- WHO defined MDS with Higher risk MDS (IPSS int-2/high)
- Azacitidine X at least 6 cycles with no hematologic improvement/no disease progression as per IWG 2006 criteria
- Ferritin >500 µg/L
- If transfusion independent, must have Hb <110 g/L OR Neutrophils < 1,000/mL OR Platelets < 100,000/mL
- ECOG ≤2
- CrCl >40 ml/min
Exclusion Criteria:
- Increased ALT (>300 U/L)
- Uncontrolled infection
- HIV+
- Pregnant or breast-feeding
- Previous and concurrent iron chelation
- Concurrent use of hematopoietic growth factors including erythropoietin, darbepoietin and granulocyte colony stimulating factor
- Concurrent use of other disease modifying agents including cytotoxic chemotherapy, histone deacetylase inhibitors, other hypomethylating agents or lenalidomide
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Deferasirox + Azacitidine
Azacitidine 75 mg/m2 daily X 7 days every 28 days for 6 cycles + Deferasirox 10-30 mg/kg/d depending on transfusion needs
|
Deferasirox: 20 mg/kg/d for < 14ml/kg/mo pRBCs (~ <4U/mo), 30mg/kg/d for ≥14ml/kg/mo pRBCs(≥4U/mo), 10mg/kg/d for transfusion-independent patients
Other Names:
Azacitidine 75mg/m2 sc daily X 7 days (5-2-2 schedule permitted) on a 28 day cycle for 6 cycles
Other Names:
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Active Comparator: Azacitidine
Azacitidine 75 mg/m2 daily X 7 days every 28 days for 6 cycles
|
Azacitidine 75mg/m2 sc daily X 7 days (5-2-2 schedule permitted) on a 28 day cycle for 6 cycles
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Difference in proportion of patients with hematologic improvement as defined by the IWG criteria30 with the addition of deferasirox to azacitidine compared with azacitidine alone in higher risk non-responding MDS patients after 6 cycles of azacitidine.
Time Frame: 6 months
|
improvement in blood counts or remission status
|
6 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Tolerability (defined by the percentage of patients able to remain on deferasirox for 6 cycles concurrent with azacitidine) and safety (type, using CTCAE version 4.0, frequency, severity, and relationship of adverse events to study therapy)
Time Frame: 6 months
|
toxicity as defined by compliance
|
6 months
|
Percentage and absolute change in serum ferritin and labile plasma iron (LPI) between baseline and end of study
Time Frame: 6 months
|
Impact of experimental arm on iron parameters
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6 months
|
Percentage change in CD34 cell intracellular reactive oxygen species (ROS) from baseline to end of study.
Time Frame: 6 months
|
Impact of experimental arm on markers of oxidative stress in the bone marrow
|
6 months
|
Percentage change in erythroid colony forming units (BFU-E and CFU-E) from baseline to end of study
Time Frame: 6 months
|
Impact of experimental arm on erythropoiesis
|
6 months
|
Percentage change in markers of DNA damage (lipid peroxidation, GSH content, and gH2AX expression), and activity of NFkappaB and Akt signaling pathways between baseline and end of study.
Time Frame: 6 months
|
Impact of experimental arm on markers of DNA damage
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6 months
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Rena Buckstein, MD, Odette Cancer Center
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
March 1, 2014
Primary Completion (Actual)
September 29, 2016
Study Completion (Actual)
September 29, 2016
Study Registration Dates
First Submitted
January 15, 2014
First Submitted That Met QC Criteria
January 15, 2014
First Posted (Estimate)
January 17, 2014
Study Record Updates
Last Update Posted (Actual)
April 26, 2018
Last Update Submitted That Met QC Criteria
April 24, 2018
Last Verified
April 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms
- Disease
- Bone Marrow Diseases
- Hematologic Diseases
- Precancerous Conditions
- Syndrome
- Myelodysplastic Syndromes
- Preleukemia
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Chelating Agents
- Sequestering Agents
- Iron Chelating Agents
- Azacitidine
- Deferasirox
Other Study ID Numbers
- CICL670ACA02T
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
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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National Cancer Institute (NCI)CompletedPreviously Treated Myelodysplastic Syndromes | Secondary Myelodysplastic Syndromes | de Novo Myelodysplastic SyndromesUnited States
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GCP-Service International West GmbHSaint-Louis Hospital, Paris, France; University of Florence; Medical University... and other collaboratorsNot yet recruitingLow Risk Myelodysplastic SyndromesSpain, Poland, Italy, Germany, France
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TJ Biopharma Co., Ltd.Recruiting
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AbbVieCelgene; Genentech, Inc.CompletedMyelodysplastic Syndromes (MDS)United States, Australia, Germany
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AbbVieGenentech, Inc.Active, not recruitingMyelodysplastic Syndromes (MDS)United States, Australia, Canada, France, Germany, Italy, United Kingdom
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The First Affiliated Hospital with Nanjing Medical...UnknownMyelodysplastic Syndromes (MDS)China
-
Sumitomo Pharma America, Inc.TerminatedMyelodysplastic Syndromes (MDS)United States
Clinical Trials on Deferasirox + Azacitidine
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Novartis PharmaceuticalsTerminated
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Groupe Francophone des MyelodysplasiesNovartisUnknown
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Novartis PharmaceuticalsCompletedTransfusion-dependent AnemiaEgypt, Hungary, Turkey, United States, Bulgaria, Italy, Belgium, Russian Federation, Philippines, France, Malaysia, India, Oman, Panama, Lebanon, Thailand, Tunisia
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DisperSol Technologies, LLCCompletedThalassemia MajorThailand, United States
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Novartis PharmaceuticalsWithdrawnThalassemia (Transfusion Delendent)
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Assistance Publique - Hôpitaux de ParisAssociation pour l'Etude des Fonctions Digestives (AEFD)UnknownPorphyria Cutanea TardaFrance
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Novartis PharmaceuticalsCompletedLow and Int 1-risk Myelodysplastic SyndromeGermany, Canada, Korea, Republic of, Sweden, Spain, China, Argentina, Italy, United Kingdom, Algeria
-
NovartisCompletedBeta-Thalassemia | HemosiderosisEgypt, Lebanon, Oman, Saudi Arabia, Syrian Arab Republic
-
Novartis PharmaceuticalsCompletedNon-transfusion Dependent ThalassemiaThailand, Turkey, Italy, Greece, China, United Kingdom, Lebanon, Tunisia