Aezea™ (cenersen) in combination with chemotherapy for the treatment of refractory acute myelogenous leukemia subjects = 55 years of age with inadequate response to a single frontline induction course randomized double-blind placebo-controlled multi-center study

• Conditions: MedDRA version: 9.1Level: LLTClassification code 10000884Term: Acute myeloid leukaemia NOS; Refractory acute myeloid leukemia

• Registration Number: EUCTR2008-002160-34-GB
• Lead Sponsor: EleosInc Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-09-04
• Last Update Posted: 24 July 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

1. In response to their initial first course of frontline treatment, patients who did not achieve a response (CR, CRi, or MLFS): a. have =15% bone marrow blasts in a BM specimen at day 14 - 30 from the initiation of the initial frontline treatment 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.
2. = 55 years old.
3. Have an understanding of the importance of not taking prohibited substances (paracetamol [acetaminophen] or antioxidants) and contract not to do so during the proscribed periods.
4. Have a life expectancy of more than 4 weeks following initiation of treatment.
5. Zubrod performance status =2.
6. Have recovered from acute toxicities of prior chemotherapy (= Grade 2).
7. Have signed an informed consent.
8. Total bilirubin =1.5 x upper normal limit (UNL) and Alanine Amino Transferase [ALT (Serum Glutamic-pyruvic Transaminase (SGPT))] =2.5 x UNL.
9. Creatinine =1.5 x UNL.
10. Serum magnesium should be within the normal range (Mg replacement being acceptable).
11. Left Ventricular Ejection Fraction (LVEF) of >50% as determined by multiple-gated acquisition scan (MUGA) or Echocardiogram (ECHO).
12. Ability to receive all courses of therapy, as outlined in the treatment schedules at the investigative site.
13. Willingness to comply with scheduled follow-up as required by the protocol.
14. Use of adequate contraceptive techniques if premenopausal and sexually active.
15. If premenopausal, have negative pregnancy tests at screening. The pregnancy test results must be known prior to enrollment.

Note: Induction course for frontline treatment must involve standard or high-dose chemotherapy. For induction regimens involving the use of ara-C in the =100 to <1000 mg/m2/day range the ara-C must have been given for at least 7 days. Induction courses of ara-C of 1000 mg/m2/day or greater for at least 3 days within a 7 day period are acceptable. Alternatively, subjects who have received an induction regimen involving the use of the experimental AML agent clofaribine with or without ara-C will be eligible for this study. Other regimens must be pre-approved by the Sponsor prior to the subject entering the trial.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Presence of uncontrolled 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, interstitial pneumonia or extensive and symptomatic interstitial fibrosis of lung, chronic liver disease or psychiatric illness/social situations that limits compliance with study requirements.
2. Aplastic or hypoplastic BM.
3. Acute promyelocytic leukemia (APL).
4. Requirement for transplant before Course 2 is complete.
5. Concurrent use of other investigational 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. However, individual cases may be considered by the Sponsor on a case-by-case basis (e.g., administration of agents used in supportive care).
6. Pregnancy (includes a positive pregnancy test at the screening visit) or lactation.
7. Known HIV infection.
8. Active hepatitis B or C or other active liver disease.
9. Presence of dyspnea at rest or with minimal exertion after correction for anemia. This is an observational assessment by the physician determined at the time of medical examination.
10. Known or suspected hypersensitivity or allergy to idarubicin or ara-C.
11. Occurrence of major surgery within two weeks of the start of Course 1. However, individual cases may be considered by the Sponsor on a case-by-case basis.
12. Chemotherapy within two weeks prior to initiation of therapy under this protocol, or hydroxyurea within 7 days.
13. Patients who, with appropriate explanation, are not prepared to commit to total avoidance of the use of paracetamol (acetaminophen) or paracetamol-containing medications during the proscribed periods (24 hours before the start of cenersen infusion (day minus 1) through the end of Course 2 (total of 57-70 days) and for one day before through the end of each of Courses 3 or 4). Non-paracetamol antipyretics and analgesics are permitted.
14. Patients not prepared to commit to the exclusion of antioxidants during times proscribed in the protocol extending from 24 hours before the start of cenersen infusion (day minus 1) through the end of chemotherapy administration for that cycle or course.
15. Medical or psychiatric conditions that compromise the ability to give informed consent, to comply with the protocol or to complete the study.
16. Inability, in the opinion of the principal investigator or clinical staff, to comply with protocol requirements for the duration of the study.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective is to determine if using cenersen along with four cycles of alternating high and low-dose chemotherapy improves the complete response (CR) rate in AML patients = 55 years of age showing inadequate response (CR, CRi, or MLFS) to a single aggressive frontline induction course (as defined in the protocol).;Secondary Objective: Overall Survival; Safety Profile; Complete Remission (CR) + Complete Remission with Incomplete Blood Count Recovery (CRi) Rate; Morphologic Leukemia-Free State (MLFS) Rate; Partial Remission Rate (PR); Remission Duration (RD); Early Deaths measured as deaths at 30, 60 and 90 days of the start of treatment; Time to Neutrophil and Platelet Recovery; Death in CR; and Quality of Life using EORTC QLQ-C30 QOL Questionnaire and Zubrod score;Primary end point(s): Complete Remission (CR) Rate