Myelodysplastic SyndromesPhase 1NCT02243124
A Study of Aezea® (Cenersen) in Transfusion Dependent Anemia Associated With Myelodysplastic Syndrome (MDS)
A Phase 1 study testing cenersen and Dexamethasone in people with Myelodysplastic Syndromes, run by Eleos, Inc. at 1 site in United States.
Trial summary
The purpose of the study is to test the safety of six cycles of cenersen treatment and to begin to test the hypothesis that intermittent administration of cenersen may lead to a reduced dependence on transfusion. Read more about this study
- Who is it for?
- Ages 18 to 95 years
- Conditions the study is for
- Myelodysplastic Syndromes
- What is being tested?
- cenersen and Dexamethasone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2014to 31 Dec 2015
- Phase
- Phase 1
- 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 to 95 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Must have histologically or cytologically confirmed diagnosis of MDS according to WHO classification that meets IPSS low to intermediate-1 risk criteria.
- For patients with del(5q) MDS, documented del(5q) MDS by metaphase cytogenetics or FISH analysis with up to 1 additional cytogenetic abnormality other than 1 involving chromosome 7 or chromosome 17.
- Demonstrated refractoriness or intolerance to standard approved therapy (lenalidomide in del(5q) MDS patients \& azanucleosides in non-del(5q)patients).
- Recovered from acute toxicities of other treatments (≤ Grade 2). All other MDS treatments discontinued at least 4 weeks prior to treatment except epoetin alpha (Procrit) 2 weeks.
- Ability to understand \& willingness to sign a written informed consent document.
- Age ≥ 18 years at time of signing informed consent form.
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- ECOG performance status ≤2.
- Life expectancy >4 weeks following initiation.
- Must meet following requirements:
- total bilirubin: ≤2 x upper normal limit (UNL) (patients with Gilbert's disease are eligible, hyperbilirubinemia is intermittent \& indirect)
- AST(SGOT)/ALT(SGPT): ≤3 x UNL
- creatinine: ≤2 x UNL
- <1% peripheral blood blasts.
- <10% bone marrow blasts.
- Medical history of RBC transfusion dependent anemia ≥4 units of RBCs during the 16 weeks prior to admin of study drug \& ≥2 units of RBCs over prior 8 weeks (day -56 to day 1 prior to treatment; baseline period) for documented Hgb of ≤ 9g/dL (during baseline). Didn't have a 56 day RBC transfusion-free period during 16 weeks prior to administration of study drug.
- Teratogenic effects of cenersen are unknown, women of child-bearing potential \& men must agree to use adequate contraception prior to study entry \& for the duration of study participation.
Who cannot join
- Receiving MDS treatment except blood transfusion and/or iron chelation within 4 weeks prior to entering study or no recovery from adverse events due to agents administered more than 4 weeks earlier.
- no current or prior use of investigational agents within 4 weeks of study entry.
- Known history of malignancy diagnosed within 2 years other than non-melanoma skin cancer.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to cenersen.
- exclude use of acetaminophen or acetaminophen-containing medications from 1 day before to 1 day after completion of treatment. The active metabolite of acetaminophen, N-acetyl-p-benzoquinone imine (NAPQI), is known to block effects of cenersen \& use of acetaminophen during treatment with study regimen has been associated with a failure to achieve a response in a past clinical trial of cenersen.
- Uncontrolled intercurrent illness that would limit compliance with study requirements.
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- Pregnant women are excluded from this study. Breastfeeding should be discontinued if the mother is treated with cenersen
- HIV-positive patients on combination antiretroviral therapy are ineligible because of unknown potential for interactions with cenersen.
- Any condition, including presence of laboratory abnormalities, which places subject at unacceptable risk if s/he were to participate in study or confounds ability to interpret data from study according to investigator assessment.
- Therapy related MDS.
- Clinically significant anemia according to investigator's assessment due to factors such as iron, B12 or folate deficiencies, autoimmune or hereditary hemolysis or gastrointestinal bleeding.
- Received hematopoietic growth factors within specified limits prior to treatment (2 weeks for epoetin alpha (Procrit) \& 4 weeks for darbepoetin alpha (Aranesp)).
- Active hepatitis B or C or other active liver disease.
- Chronic use (>2 weeks) of greater than physiologic doses of corticosteroid agent (dose equivalent to ≥10mg of prednisone) within 28 days of 1st day of study drug treatment \& during treatment
Trial locations and contacts
1 site in 1 country.
United States1 site
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, 33612
About this study
Official title: A Study of Aezea® (Cenersen) in Transfusion Dependent Anemia Associated With Myelodysplastic Syndrome
The purpose of the study is to test the safety of six cycles of cenersen treatment and to begin to test the hypothesis that intermittent administration of cenersen may lead to a reduced dependence on transfusion.
Read the detailed description
The study is a nonrandomized open-label treatment with varying doses of cenersen by intravenous administration to:
Primary
*To assess the safety profile and dose limiting toxicities (DLT) of cenersen for each of three increasing dose levels as stipulated by the protocol in patients with lower risk MDS defined as low or intermediate-1 risk by IPSS.
Secondary
- To determine the lowest pharmacologically active exposure from among three increasing dose levels as stipulated by the protocol that exhibits the desired activity on erythropoiesis after evaluation of all dose levels, and
- To determine if intermittent treatment with cenersen will reduce transfusion requirements for patients with lower risk MDS.
- Conditions
- Myelodysplastic Syndromes
- Being tested
- cenersen, Dexamethasone
- Keywords
- Anemia, Transfusion, AML, MDS, CLL, p53, erythropoiesis
- Medical subject headings
- Myelodysplastic Syndromes, Anemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cenersenDrug
Also called Ol(1)p53, EL625, Aezea
cenersen is a phosphorothioate antisense oligonucleotide that down-regulates the production of both wild-type and mutant p53, and has a RNase H-dependent mechanism of action
DexamethasoneDrug
Also called Decadron, Maxidex, Ozurdex, Baycadron
Optionally, Dexamethasone 20 mg po weekly can be added after week 16 if stable disease but no HI is observed.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Active comparator | cenersen IV infusion 0.3 mg/kg/day (0.1 mg/kg/h x 3 h x 4 days) for 6 cycles Administration of study drug will be over 4 consecutive days at the outset of each 28 day cycle for a total of 6 cycles for each patient. Dexamethasone 20 mg po weekly can be added after week 16 if stable disease but no Hematologic Improvement (HI) is observed. Receives: Drug: cenersen; Drug: Dexamethasone |
| Group 2 | Active comparator | cenersen IV infusion 0.6 mg/kg/day (0.2 mg/kg/h x 3 h x 4 days) for 6 cycles Administration of study drug will be over 4 consecutive days at the outset of each 28 day cycle for a total of 6 cycles for each patient. Dexamethasone 20 mg po weekly can be added after week 16 if stable disease but no HI is observed. Receives: Drug: cenersen; Drug: Dexamethasone |
| Group 3 | Active comparator | cenersen IV infusion 1.2 mg/kg/day (0.4 mg/kg/h x 3 h x 4 days) for 6 cycles Administration of study drug will be over 4 consecutive days at the outset of each 28 day cycle for a total of 6 cycles for each patient. Dexamethasone 20 mg po weekly can be added after week 16 if stable disease but no HI is observed. Receives: Drug: cenersen; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
1) Interventional Drug Safety: dose limiting toxicities (DLT) of cenersen for each of three increasing dose levels as stipulated by the protocol in patients with lower risk MDS defined as low or intermediate-1 risk by IPSS.
Assessment of adverse events for each dosing level
Measured: 6 months w/ 24 month follow-up
Secondary outcomes (2)
Reduction in RBC transfusions
Erythroid Response (HI-E) from the lowest pharmacologically active exposure after evaluation of all dose levels - Reduction in RBC transfusions by greater than or equal to 4 units/8 weeks triggered by a hemoglobin transfusion threshold lower than 9 g/dL when compared to the 8 week baseline for transfusion-dependent patients (where transfusion dependence is defined as 4 units or more RBCs in 8 weeks)
Measured: 6 months w/ 24month follow-up
Improvement in Hemoglobin (Hb) levels
Hematologic Improvement by Hb increase by ≥ 1.5 g/dL or more for at least 8 weeks and the patient is not transfusion-dependent.
Measured: 6 months w/ 24 month follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2014 (estimated)
- Study startSep 2014
- Primary completion30 Sep 2015
- Study completion31 Dec 2015
Why it stopped: Company went out of business
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Myelodysplastic SyndromesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eleos, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- H. Lee Moffitt Cancer Center and Research Institute
- Responsible party
- Sponsor
- Investigators
- Rami Komrokji, MD, Principal investigator, H. Lee Moffitt Cancer Center and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02243124
- Sponsor's protocol ID
- MDS ELP9001
- Status last verified
- Jan 2017
- First submitted
- 11 Sep 2014
- Last updated
- 21 Feb 2021
- Results posted
- No
- Data monitoring committee
- No
Publications
Caceres G, McGraw K, Yip BH, Pellagatti A, Johnson J, Zhang L, Liu K, Zhang LM, Fulp WJ, Lee JH, Al Ali NH, Basiorka A, Smith LJ, Daugherty FJ, Littleton N, Wells RA, Sokol L, Wei S, Komrokji RS, Boultwood J, List AF. TP53 suppression promotes erythropoiesis in del(5q) MDS, suggesting a targeted therapeutic strategy in lenalidomide-resistant patients. Proc Natl Acad Sci U S A. 2013 Oct 1;110(40):16127-32. doi: 10.1073/pnas.1311055110. Epub 2013 Sep 16.
PubMed 24043769
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study of Aezea® (Cenersen) in Transfusion Dependent Anemia Associated With Myelodysplastic Syndrome
- ClinicalTrials.gov ID
- NCT02243124
- Acronym / sponsor ID
- MDS ELP9001
- Conditions
- Myelodysplastic Syndromes
- Keywords
- Anemia, Transfusion, AML, MDS, CLL, p53, erythropoiesis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Company went out of business
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Eleos, Inc.Industry (pharma, biotech, devices)
- Collaborators
- H. Lee Moffitt Cancer Center and Research Institute
- Study start
- Sep 2014
- Primary completion
- 30 Sep 2015 (actual)
- Study completion
- 31 Dec 2015 (actual)
- First posted
- 17 Sep 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study is to test the safety of six cycles of cenersen treatment and to begin to test the hypothesis that intermittent administration of cenersen may lead to a reduced dependence on transfusion.
Detailed description
The study is a nonrandomized open-label treatment with varying doses of cenersen by intravenous administration to:
Primary
*To assess the safety profile and dose limiting toxicities (DLT) of cenersen for each of three increasing dose levels as stipulated by the protocol in patients with lower risk MDS defined as low or intermediate-1 risk by IPSS.
Secondary
- To determine the lowest pharmacologically active exposure from among three increasing dose levels as stipulated by the protocol that exhibits the desired activity on erythropoiesis after evaluation of all dose levels, and
- To determine if intermittent treatment with cenersen will reduce transfusion requirements for patients with lower risk MDS.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Active comparator | Drug: cenersen, Drug: Dexamethasonecenersen IV infusion 0.3 mg/kg/day (0.1 mg/kg/h x 3 h x 4 days) for 6 cycles Administration of study drug will be over 4 consecutive days at the outset of each 28 day cycle for a total of 6 cycles for each patient. Dexamethasone 20 mg po weekly can be added after week 16 if stable disease but no Hematologic Improvement (HI) is observed. |
| Group 2 | Active comparator | Drug: cenersen, Drug: Dexamethasonecenersen IV infusion 0.6 mg/kg/day (0.2 mg/kg/h x 3 h x 4 days) for 6 cycles Administration of study drug will be over 4 consecutive days at the outset of each 28 day cycle for a total of 6 cycles for each patient. Dexamethasone 20 mg po weekly can be added after week 16 if stable disease but no HI is observed. |
| Group 3 | Active comparator | Drug: cenersen, Drug: Dexamethasonecenersen IV infusion 1.2 mg/kg/day (0.4 mg/kg/h x 3 h x 4 days) for 6 cycles Administration of study drug will be over 4 consecutive days at the outset of each 28 day cycle for a total of 6 cycles for each patient. Dexamethasone 20 mg po weekly can be added after week 16 if stable disease but no HI is observed. |
Who may qualify
- Ages
- 18 to 95 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Must have histologically or cytologically confirmed diagnosis of MDS according to WHO classification that meets IPSS low to intermediate-1 risk criteria.
- For patients with del(5q) MDS, documented del(5q) MDS by metaphase cytogenetics or FISH analysis with up to 1 additional cytogenetic abnormality other than 1 involving chromosome 7 or chromosome 17.
- Demonstrated refractoriness or intolerance to standard approved therapy (lenalidomide in del(5q) MDS patients \& azanucleosides in non-del(5q)patients).
- Recovered from acute toxicities of other treatments (≤ Grade 2). All other MDS treatments discontinued at least 4 weeks prior to treatment except epoetin alpha (Procrit) 2 weeks.
- Ability to understand \& willingness to sign a written informed consent document.
Key exclusion criteria (14 listed)
- Receiving MDS treatment except blood transfusion and/or iron chelation within 4 weeks prior to entering study or no recovery from adverse events due to agents administered more than 4 weeks earlier.
- no current or prior use of investigational agents within 4 weeks of study entry.
- Known history of malignancy diagnosed within 2 years other than non-melanoma skin cancer.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to cenersen.
- exclude use of acetaminophen or acetaminophen-containing medications from 1 day before to 1 day after completion of treatment. The active metabolite of acetaminophen, N-acetyl-p-benzoquinone imine (NAPQI), is known to block effects of cenersen \& use of acetaminophen during treatment with study regimen has been associated with a failure to achieve a response in a past clinical trial of cenersen.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cenersenAlso: Ol(1)p53, EL625, Aezeacenersen is a phosphorothioate antisense oligonucleotide that down-regulates the production of both wild-type and mutant p53, and has a RNase H-dependent mechanism of action | Drug | Group 1, Group 2, Group 3 |
| DexamethasoneAlso: Decadron, Maxidex, Ozurdex, BaycadronOptionally, Dexamethasone 20 mg po weekly can be added after week 16 if stable disease but no HI is observed. | Drug | Group 1, Group 2, Group 3 |
Primary outcome
1) Interventional Drug Safety: dose limiting toxicities (DLT) of cenersen for each of three increasing dose levels as stipulated by the protocol in patients with lower risk MDS defined as low or intermediate-1 risk by IPSS.
Time frame: 6 months w/ 24 month follow-up
Assessment of adverse events for each dosing level
2 secondary outcomes
Reduction in RBC transfusions
Time frame: 6 months w/ 24month follow-up
Improvement in Hemoglobin (Hb) levels
Time frame: 6 months w/ 24 month follow-up
Results and safety
The study was stopped early (reason given: Company went out of business). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2021.
- Background: PubMed 24043769Caceres G, McGraw K, Yip BH, Pellagatti A, Johnson J, Zhang L, Liu K, Zhang LM, Fulp WJ, Lee JH, Al Ali NH, Basiorka A, Smith LJ, Daugherty FJ, Littleton N, Wells RA, Sokol L, Wei S, Komrokji RS, Boultwood J, List AF. TP53 suppression promotes erythropoiesis in del(5q) MDS, suggesting a targeted therapeutic strategy in lenalidomide-resistant patients. Proc Natl Acad Sci U S A. 2013 Oct 1;110(40):16127-32. doi: 10.1073/pnas.1311055110. Epub 2013 Sep 16.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rami Komrokji, MD principal investigator
H. Lee Moffitt Cancer Center and Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing cenersen and Dexamethasone in people with Myelodysplastic Syndromes, run by Eleos, Inc. at 1 site in United States.
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 16 inclusion and 14 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 21 Feb 2021. 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 United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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: Company went out of business). 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?
1) Interventional Drug Safety: dose limiting toxicities (DLT) of cenersen for each of three increasing dose levels as stipulated by the protocol in patients with lower risk MDS defined as low or intermediate-1 risk by IPSS. (time frame: 6 months w/ 24 month follow-up). 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 NCT02243124, which also lists 1 linked publication.
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 21 Feb 2021.