Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Azacitidine Plus Deferasirox (ICL670) in Higher Risk Myelodysplastic Syndromes (MDS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02038816
Recruitment Status : Terminated (accrual too slow, insufficient patients)
First Posted : January 17, 2014
Last Update Posted : April 26, 2018
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
Sunnybrook Health Sciences Centre

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Myelodysplastic Syndromes Drug: Deferasirox + Azacitidine Drug: Azacitidine Phase 2

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

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A PHASE II STUDY OF Azacitidine Plus Deferasirox (ICL670) in Higher Risk Myelodysplastic Syndromes (MDS)
Study Start Date : March 2014
Actual Primary Completion Date : September 29, 2016
Actual Study Completion Date : September 29, 2016

Resource links provided by the National Library of Medicine


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
Drug: Deferasirox + Azacitidine

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:
  • Exjade
  • Vidaza

Drug: Azacitidine
Azacitidine 75mg/m2 sc daily X 7 days (5-2-2 schedule permitted) on a 28 day cycle for 6 cycles
Other Name: Vidaza

Active Comparator: Azacitidine
Azacitidine 75 mg/m2 daily X 7 days every 28 days for 6 cycles
Drug: Azacitidine
Azacitidine 75mg/m2 sc daily X 7 days (5-2-2 schedule permitted) on a 28 day cycle for 6 cycles
Other Name: Vidaza




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02038816


Locations
Layout table for location information
Canada, Ontario
Odette Cancer Centre, Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada, M4N 3M5
Sponsors and Collaborators
Sunnybrook Health Sciences Centre
Novartis
Investigators
Layout table for investigator information
Principal Investigator: Rena Buckstein, MD Odette Cancer Center

Layout table for additonal information
Responsible Party: Sunnybrook Health Sciences Centre
ClinicalTrials.gov Identifier: NCT02038816     History of Changes
Other Study ID Numbers: CICL670ACA02T
First Posted: January 17, 2014    Key Record Dates
Last Update Posted: April 26, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
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
Additional relevant MeSH terms:
Layout table for MeSH terms
Preleukemia
Myelodysplastic Syndromes
Syndrome
Disease
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Azacitidine
Deferasirox
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors
Iron Chelating Agents
Chelating Agents
Sequestering Agents