Aezea® (Cenersen) and Chemotherapy for AML Subjects ≥ 55 Years of Age With No Response to Frontline Induction Course

This study has been withdrawn prior to enrollment.
(Study Was Terminated due to lack of Funding.)
Sponsor:
Information provided by (Responsible Party):
Eleos, Inc.
ClinicalTrials.gov Identifier:
NCT00967512
First received: August 26, 2009
Last updated: September 16, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Acute Myelogenous Leukemia
Drug: cenersen
Drug: placebo
Drug: idarubicin, cytarabine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Eleos, Inc.:

Primary Outcome Measures:
  • Complete Remission Rate [ Time Frame: within day 28-42 of Course 1, and within day 28-42 of Course 2 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Safety Profile [ Time Frame: up to 2 years ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • Morphologic Leukemia-Free State Rate [ Time Frame: within day 28-42 of Course 1, and within day 28-42 of Course 2 ] [ Designated as safety issue: No ]
  • Partial Remission Rate [ Time Frame: within day 28-42 of Course 1, and within day 28-42 of Course 2 ] [ Designated as safety issue: No ]
  • Remission Duration [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Time to Neutrophil and Platelet Recovery [ Time Frame: within day 28-42 of Course 1, and within day 28-42 of Course 2 ] [ Designated as safety issue: No ]
  • Death in Complete Remission [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: January 2012
Study Completion Date: January 2012
Estimated Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: cenersen, idarubicin, cytarabine
cenersen, idarubicin, cytarabine
Drug: cenersen
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
Other Names:
  • Aezea®
  • cenersen sodium
  • EL625
Drug: idarubicin, cytarabine
idarubicin, cytarabine
Other Names:
  • idamycin
  • Ara-C
Placebo Comparator: placebo, idarubicin, cytarabine
placebo, idarubicin, cytarabine
Drug: placebo
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
Other Name: saline
Drug: idarubicin, cytarabine
idarubicin, cytarabine
Other Names:
  • idamycin
  • Ara-C

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.

  Eligibility

Ages Eligible for Study:   55 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • 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

Exclusion Criteria:

  • 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
  • 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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00967512

Sponsors and Collaborators
Eleos, Inc.
Investigators
Study Chair: Larry J Smith, PhD Eleos, Inc.
  More Information

No publications provided

Responsible Party: Eleos, Inc.
ClinicalTrials.gov Identifier: NCT00967512     History of Changes
Other Study ID Numbers: ELP1020, 2008-002160-34
Study First Received: August 26, 2009
Last Updated: September 16, 2014
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Eleos, Inc.:
Oligonucleotides, Antisense
Tumor Suppressor Protein p53
idarubicin
cytarabine

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Idarubicin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on October 02, 2014