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

NCT00967512 | Withdrawn Phase 2

• 2 other identifiers: ELP10202008-002160-34
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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 aggressive frontline induction course.

Conditions

Acute Myelogenous Leukemia

Keywords

Oligonucleotides, Antisense; Tumor Suppressor Protein p53; idarubicin; cytarabine

Outcome Measures

Primary Outcomes (1)

• Complete Remission Rate

  within day 28-42 of Course 1, and within day 28-42 of Course 2

Secondary Outcomes (10)

• Overall Survival

  2 years

• Safety Profile

  up to 2 years

• Complete Remission + Complete Remission with Incomplete Blood Count Recovery Rate

  within day 28-42 of Course 1, and within day 28-42 of Course 2

• Morphologic Leukemia-Free State Rate

  within day 28-42 of Course 1, and within day 28-42 of Course 2

• Partial Remission Rate

  within day 28-42 of Course 1, and within day 28-42 of Course 2

Study Arms (2)

cenersen, idarubicin, cytarabine

EXPERIMENTAL

cenersen, idarubicin, cytarabine

Drug: cenersen; Drug: idarubicin, cytarabine

placebo, idarubicin, cytarabine

PLACEBO COMPARATOR

placebo, idarubicin, cytarabine

Drug: placebo; Drug: idarubicin, cytarabine

Interventions

cenersen DRUG

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

Also known as: Aezea®, cenersen sodium, EL625

cenersen, idarubicin, cytarabine

placebo DRUG

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

Also known as: saline

placebo, idarubicin, cytarabine

idarubicin, cytarabine DRUG

idarubicin, cytarabine

Also known as: idamycin, Ara-C

cenersen, idarubicin, cytarabine; placebo, idarubicin, cytarabine

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Eleos, Inc.: lead

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

cenersen; Sodium Chloride; Idarubicin; Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Larry J Smith, PhD

  Eleos, Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2009
• First Posted: August 28, 2009
• Study Start: January 1, 2012
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2012
• Last Updated: September 18, 2014

Record last verified: 2014-09