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

Sponsor

Eleos, Inc. (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT00967512

Collaborator

(none)

Enrollment

Arms

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myelogenous Leukemia	Drug: cenersen Drug: placebo Drug: idarubicin, cytarabine	Phase 2

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

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, 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

Study Start Date :

Jan 1, 2012

Anticipated Primary Completion Date :

Jan 1, 2012

Actual Study Completion Date :

Jan 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
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 Names: saline Drug: idarubicin, cytarabine idarubicin, cytarabine Other Names: idamycin Ara-C

Arm

Intervention/Treatment

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 Names:

saline

Drug: idarubicin, cytarabine

idarubicin, cytarabine

Other Names:

idamycin

Ara-C

Outcome Measures

Primary Outcome Measures

Complete Remission Rate [within day 28-42 of Course 1, and within day 28-42 of Course 2]

Secondary Outcome Measures

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]
Remission Duration [2 years]
Early deaths measured as deaths at 30, 60 and 90 days of the start of treatment [30, 90, and 90 days from start of treatment]
Time to Neutrophil and Platelet Recovery [within day 28-42 of Course 1, and within day 28-42 of Course 2]
Death in Complete Remission [2 years]
Zubrod Score [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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

55 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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