Acute Myelogenous LeukemiaPhase 2NCT00967512
Aezea® (Cenersen) and Chemotherapy for AML Subjects ≥ 55 Years of Age With No Response to Frontline Induction Course
A Phase 2 study testing cenersen and idarubicin, cytarabine in people with Acute Myelogenous Leukemia, run by Eleos, Inc..
Trial summary
The purpose of this study is to assess whether treatment with cenersen in combination with 4 cycles of high and low-dose chemotherapy (idarubicin and cytarabine) improves the complete response rate in acute myelogenous leukemia (AML) patients ≥ 55 years of age who did not show a response (CR, CRi, or PR) to a single… Read more about this study
- Who is it for?
- Ages 55 years and older
- Conditions the study is for
- Acute Myelogenous Leukemia
- What is being tested?
- cenersen and idarubicin, cytarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jan 2012to Jan 2012
- 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 55 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- In response to their first course of frontline treatment, patients who did not achieve a response (CR, CRi, or PR) and have ≥ 15% bone marrow blasts in a BM specimen between day 14 - 42 from the initiation of a single frontline course. If within that timeframe the BM is hypoplastic, the BM assessment can be repeated within a subsequent two-week period and the patient entered into the study if there is ≥ 15% blasts in the bone marrow.
- ≥ 55 years old
- Have an understanding of the importance of not taking paracetamol (acetaminophen) or high dose antioxidants from 1 day before through 1 day after treatment during any given course
- Have a life expectancy of more than 4 weeks following initiation of treatment
- Secondary AML is allowed as are antecedent hematologic disorders
- Zubrod performance status ≤ 2
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- Have recovered from acute toxicities of prior chemotherapy (≤ Grade 2)
- Have signed an informed consent
- Total bilirubin ≤ 1.5 x upper normal limit (UNL) and Alanine Amino Transferase [ALT (Serum Glutamic-pyruvic Transaminase (SGPT))] ≤ 2.5 x UNL
- Creatinine ≤ 1.5 x UNL
- Serum magnesium should be within the normal range (Mg replacement being acceptable)
- Left Ventricular Ejection Fraction (LVEF) of >50% as determined by multiple-gated acquisition scan (MUGA) or Echocardiogram (ECHO)
- Ability to receive all courses of therapy, as outlined in the treatment schedules at the investigative site
- Willingness to comply with scheduled follow-up as required by the protocol
- Use of adequate contraceptive techniques if premenopausal and sexually active; examples include implantable, injectable or oral contraceptives, intrauterine devices (IUD), sterilization, or sexual abstinence
- If premenopausal, have negative pregnancy tests at screening
Who cannot join
- Presence of any pneumonia regardless of severity or other life-threatening illness including, but not limited to, ongoing infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, high blood pressure, history of labile hypertension, history of poor compliance with an antihypertensive regimen, myocardial infarction less than or equal to 6 months prior to registration, diabetes, or extensive and symptomatic interstitial fibrosis of lung, chronic liver disease or psychiatric illness/social situations that limits compliance with study requirements
- Acute promyelocytic leukemia (APL [FAB classification M3])
- Requirement for transplant before Course 2 is complete
- Concurrent use of other experimental agents (i.e., drugs not approved for clinical indications) or having received other investigational agents within the 30 days prior to the start of Course 1
- Pregnancy (includes a positive pregnancy test at the screening visit) or lactation
- Known HIV infection
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- Active hepatitis B or C or other active liver disease
- Presence of dyspnea at rest or with minimal exertion after correction for anemia
- Known or suspected hypersensitivity or allergy to idarubicin or ara-C
- Occurrence of major surgery within two weeks of the start of Course 1
- Chemotherapy within two weeks prior to initiation of therapy under this protocol, or hydroxyurea within 7 days
- Patients who, with appropriate explanation, are not prepared to exclude the use of paracetamol (acetaminophen) or paracetamol-containing medications from 1 day before through 1 day after treatment during any course
- Patients who are not prepared to commit to the exclusion of high dose antioxidants from 1 day before through 1 day after treatment during any given course
- Medical or psychiatric conditions that compromise the ability to give informed consent, to comply with the protocol or to complete the study
- Inability, in the opinion of the principal investigator or clinical staff, to comply with protocol requirements for the duration of the study
About this study
Official title: Aezea (Cenersen) in Combination With Chemotherapy for Treatment of Acute Myelogenous Leukemia Subjects ≥55 Years of Age With No Response to Single Frontline Induction Course in a Randomized Double-Blind Placebo-Controlled Multi-Center Study
The purpose of this study is to assess whether treatment with cenersen in combination with 4 cycles of high and low-dose chemotherapy (idarubicin and cytarabine) improves the complete response rate in acute myelogenous leukemia (AML) patients ≥ 55 years of age who did not show a response (CR, CRi, or PR) to a single aggressive frontline induction course.
Read the detailed description
Cenersen is a phosphorothioate antisense oligonucleotide of sequence 5'-CCCTG5-CTCCC10-CCCTG15-GCTCC20-3'. For AML, cenersen is specific for blocking p53 expression in the stem cells. When AML stem cells are dividing, cenersen sensitizes them to even low-level DNA damage of the type caused by idarubicin, etoposide and possibly ara-C.
Because AML stem cells are not all dividing at any given time, this protocol is designed to treat patients with a total of four cycles of cenersen plus chemotherapy within a two to three month period. For a limited period of time, proliferating non-stem cells can be expected to maintain or even expand the tumor while the stem cells are being depleted. If the proliferating non-stem cells are not resupplied by the stem cells, they will all become end stage blasts after a few divisions and undergo elimination.
- Conditions
- Acute Myelogenous Leukemia
- Being tested
- cenersen, placebo, idarubicin, cytarabine
- Keywords
- Oligonucleotides, Antisense, Tumor Suppressor Protein p53, idarubicin, cytarabine
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cenersenDrug
Also called Aezea®, cenersen sodium, EL625
solution for injection, intravenous infusion, 0.1 mg/kg/h x 24h x 4 days, and 0.4 mg/kg/h x 3h x 4 days
placeboDrug
Also called saline
solution for injection, intravenous infusion, 0.1 mg/kg/h x 24h x 4 days, and 0.4 mg/kg/h x 3h x 4 days
idarubicin, cytarabineDrug
Also called idamycin, Ara-C
idarubicin, cytarabine
| Study group | Role | What they receive |
|---|---|---|
| cenersen, idarubicin, cytarabine | Experimental | cenersen, idarubicin, cytarabine Receives: Drug: cenersen; Drug: idarubicin, cytarabine |
| placebo, idarubicin, cytarabine | Placebo comparator | placebo, idarubicin, cytarabine Receives: Drug: placebo; Drug: idarubicin, cytarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete Remission Rate
Measured: within day 28-42 of Course 1, and within day 28-42 of Course 2
Secondary outcomes (10)
Overall Survival
Measured: 2 years
Safety Profile
Measured: up to 2 years
Complete Remission + Complete Remission with Incomplete Blood Count Recovery Rate
Measured: within day 28-42 of Course 1, and within day 28-42 of Course 2
Morphologic Leukemia-Free State Rate
Measured: within day 28-42 of Course 1, and within day 28-42 of Course 2
Partial Remission Rate
Measured: within day 28-42 of Course 1, and within day 28-42 of Course 2
Remission Duration
Measured: 2 years
Early deaths measured as deaths at 30, 60 and 90 days of the start of treatment
Measured: 30, 90, and 90 days from start of treatment
Time to Neutrophil and Platelet Recovery
Measured: within day 28-42 of Course 1, and within day 28-42 of Course 2
Death in Complete Remission
Measured: 2 years
Zubrod Score
Measured: during Frontline Assessment (screening); Course 1: on days 6, 15, 18, and within day 28-42; Course 2: on days 1, 7, 15, 18, and within day 28-42; Course 3: on days 1 and 6; and Course 4: on days 1 and 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2009 (estimated)
- Study startJan 2012
- Primary completionJan 2012 (estimated)
- Study completionJan 2012
Why it stopped: Study Was Terminated due to lack of Funding.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myelogenous LeukemiaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eleos, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Larry J Smith, PhD, Study chair, Eleos, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00967512
- Sponsor's protocol ID
- ELP1020
- Other IDs
- 2008-002160-34, 2008
- Status last verified
- Sep 2014
- First submitted
- 26 Aug 2009
- Last updated
- 18 Sep 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Aezea (Cenersen) in Combination With Chemotherapy for Treatment of Acute Myelogenous Leukemia Subjects ≥55 Years of Age With No Response to Single Frontline Induction Course in a Randomized Double-Blind Placebo-Controlled Multi-Center Study
- ClinicalTrials.gov ID
- NCT00967512
- Acronym / sponsor ID
- ELP1020
- Conditions
- Acute Myelogenous Leukemia
- Keywords
- Oligonucleotides, Antisense, Tumor Suppressor Protein p53, idarubicin, cytarabine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study Was Terminated due to lack of Funding.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Eleos, Inc.Industry (pharma, biotech, devices)
- Study start
- Jan 2012
- Primary completion
- Jan 2012 (estimated)
- Study completion
- Jan 2012 (actual)
- First posted
- 28 Aug 2009 (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 this study is to assess whether treatment with cenersen in combination with 4 cycles of high and low-dose chemotherapy (idarubicin and cytarabine) improves the complete response rate in acute myelogenous leukemia (AML) patients ≥ 55 years of age who did not show a response (CR, CRi, or PR) to a single aggressive frontline induction course.
Detailed description
Cenersen is a phosphorothioate antisense oligonucleotide of sequence 5'-CCCTG5-CTCCC10-CCCTG15-GCTCC20-3'. For AML, cenersen is specific for blocking p53 expression in the stem cells. When AML stem cells are dividing, cenersen sensitizes them to even low-level DNA damage of the type caused by idarubicin, etoposide and possibly ara-C.
Because AML stem cells are not all dividing at any given time, this protocol is designed to treat patients with a total of four cycles of cenersen plus chemotherapy within a two to three month period. For a limited period of time, proliferating non-stem cells can be expected to maintain or even expand the tumor while the stem cells are being depleted. If the proliferating non-stem cells are not resupplied by the stem cells, they will all become end stage blasts after a few divisions and undergo elimination.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| cenersen, idarubicin, cytarabine | Experimental | Drug: cenersen, Drug: idarubicin, cytarabinecenersen, idarubicin, cytarabine |
| placebo, idarubicin, cytarabine | Placebo comparator | Drug: placebo, Drug: idarubicin, cytarabineplacebo, idarubicin, cytarabine |
Who may qualify
- Ages
- 55 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- In response to their first course of frontline treatment, patients who did not achieve a response (CR, CRi, or PR) and have ≥ 15% bone marrow blasts in a BM specimen between day 14 - 42 from the initiation of a single frontline course. If within that timeframe the BM is hypoplastic, the BM assessment can be repeated within a subsequent two-week period and the patient entered into the study if there is ≥ 15% blasts in the bone marrow.
- ≥ 55 years old
- Have an understanding of the importance of not taking paracetamol (acetaminophen) or high dose antioxidants from 1 day before through 1 day after treatment during any given course
- Have a life expectancy of more than 4 weeks following initiation of treatment
- Secondary AML is allowed as are antecedent hematologic disorders
Key exclusion criteria (15 listed)
- Presence of any pneumonia regardless of severity or other life-threatening illness including, but not limited to, ongoing infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, high blood pressure, history of labile hypertension, history of poor compliance with an antihypertensive regimen, myocardial infarction less than or equal to 6 months prior to registration, diabetes, or extensive and symptomatic interstitial fibrosis of lung, chronic liver disease or psychiatric illness/social situations that limits compliance with study requirements
- Acute promyelocytic leukemia (APL [FAB classification M3])
- Requirement for transplant before Course 2 is complete
- Concurrent use of other experimental agents (i.e., drugs not approved for clinical indications) or having received other investigational agents within the 30 days prior to the start of Course 1
- Pregnancy (includes a positive pregnancy test at the screening visit) or lactation
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: Aezea®, cenersen sodium, EL625solution for injection, intravenous infusion, 0.1 mg/kg/h x 24h x 4 days, and 0.4 mg/kg/h x 3h x 4 days | Drug | cenersen, idarubicin, cytarabine |
| placeboAlso: salinesolution for injection, intravenous infusion, 0.1 mg/kg/h x 24h x 4 days, and 0.4 mg/kg/h x 3h x 4 days | Drug | placebo, idarubicin, cytarabine |
| idarubicin, cytarabineAlso: idamycin, Ara-Cidarubicin, cytarabine | Drug | cenersen, idarubicin, cytarabine, placebo, idarubicin, cytarabine |
Primary outcome
Complete Remission Rate
Time frame: within day 28-42 of Course 1, and within day 28-42 of Course 2
10 secondary outcomes
Overall Survival
Time frame: 2 years
Safety Profile
Time frame: up to 2 years
Complete Remission + Complete Remission with Incomplete Blood Count Recovery Rate
Time frame: within day 28-42 of Course 1, and within day 28-42 of Course 2
Morphologic Leukemia-Free State Rate
Time frame: within day 28-42 of Course 1, and within day 28-42 of Course 2
Partial Remission Rate
Time frame: within day 28-42 of Course 1, and within day 28-42 of Course 2
Remission Duration
Time frame: 2 years
Early deaths measured as deaths at 30, 60 and 90 days of the start of treatment
Time frame: 30, 90, and 90 days from start of treatment
Time to Neutrophil and Platelet Recovery
Time frame: within day 28-42 of Course 1, and within day 28-42 of Course 2
Death in Complete Remission
Time frame: 2 years
Zubrod Score
Time frame: during Frontline Assessment (screening); Course 1: on days 6, 15, 18, and within day 28-42; Course 2: on days 1, 7, 15, 18, and within day 28-42; Course 3: on days 1 and 6; and Course 4: on days 1 and 6
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2014.
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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.
Larry J Smith, PhD study chair
Eleos, Inc.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing cenersen and idarubicin, cytarabine in people with Acute Myelogenous Leukemia, run by Eleos, Inc..
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 15 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: withdrawn, as of the sponsor's last update on 18 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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 withdrawn before enrolling participants, so there are no results.
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?
Complete Remission Rate (time frame: within day 28-42 of Course 1, and within day 28-42 of Course 2). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Sep 2014.