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Myelodysplastic SyndromesPhase 2NCT02038816

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

A Phase 2 study testing Deferasirox + Azacitidine and Azacitidine in people with Myelodysplastic Syndromes, run by Sunnybrook Health Sciences Centre at 1 site in Canada.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Myelodysplastic Syndromes
What is being tested?
Deferasirox + Azacitidine and Azacitidine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
1 siteCanada
Study dates
Mar 2014to 29 Sep 2016
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

Canada1 site

  • Odette Cancer Centre, Sunnybrook Health Sciences Centre

    Toronto, Ontario, M4N 3M5

Other trials in Canada

About this study

Official title: 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.

Read the 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

Being tested
Deferasirox + Azacitidine, Azacitidine
Medical subject headings
Myelodysplastic Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Deferasirox + AzacitidineDrug

    Also called Exjade, Vidaza

    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

  • AzacitidineDrug

    Also called Vidaza

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

Study groups in NCT02038816
Study groupRoleWhat they receive
Deferasirox + AzacitidineExperimentalAzacitidine 75 mg/m2 daily X 7 days every 28 days for 6 cycles + Deferasirox 10-30 mg/kg/d depending on transfusion needs
Receives: Drug: Deferasirox + Azacitidine; Drug: Azacitidine
AzacitidineActive comparatorAzacitidine 75 mg/m2 daily X 7 days every 28 days for 6 cycles
Receives: Drug: Azacitidine

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    improvement in blood counts or remission status

    Measured: 6 months

Secondary outcomes (5)

  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)

    toxicity as defined by compliance

    Measured: 6 months

  2. Percentage and absolute change in serum ferritin and labile plasma iron (LPI) between baseline and end of study

    Impact of experimental arm on iron parameters

    Measured: 6 months

  3. Percentage change in CD34 cell intracellular reactive oxygen species (ROS) from baseline to end of study.

    Impact of experimental arm on markers of oxidative stress in the bone marrow

    Measured: 6 months

  4. Percentage change in erythroid colony forming units (BFU-E and CFU-E) from baseline to end of study

    Impact of experimental arm on erythropoiesis

    Measured: 6 months

  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.

    Impact of experimental arm on markers of DNA damage

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Jan 2014 (estimated)
  2. Study startMar 2014
  3. Primary completion29 Sep 2016
  4. Study completion29 Sep 2016

Why it stopped: accrual too slow, insufficient patients

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02038816
Sponsor's protocol ID
CICL670ACA02T
Status last verified
Apr 2018
First submitted
15 Jan 2014
Last updated
26 Apr 2018
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Deferasirox + Azacitidine and Azacitidine in people with Myelodysplastic Syndromes, run by Sunnybrook Health Sciences Centre at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 26 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: accrual too slow, insufficient patients). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02038816.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Apr 2018.

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