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cenersen IV infusion 0.3 mg/kg/day (0.1 mg/kg/h x 3 h x 4 days) for 6 cycles Administration of study drug will be over 4 consecutive days at the outset of each 28 day cycle for a total of 6 cycles for each patient. Dexamethasone 20 mg po weekly can be added after week 16 if stable disease but no Hematologic Improvement (HI) is observed.

cenersen IV infusion 0.6 mg/kg/day (0.2 mg/kg/h x 3 h x 4 days) for 6 cycles Administration of study drug will be over 4 consecutive days at the outset of each 28 day cycle for a total of 6 cycles for each patient. Dexamethasone 20 mg po weekly can be added after week 16 if stable disease but no HI is observed.

cenersen IV infusion 1.2 mg/kg/day (0.4 mg/kg/h x 3 h x 4 days) for 6 cycles Administration of study drug will be over 4 consecutive days at the outset of each 28 day cycle for a total of 6 cycles for each patient. Dexamethasone 20 mg po weekly can be added after week 16 if stable disease but no HI is observed.

cenersen is a phosphorothioate antisense oligonucleotide that down-regulates the production of both wild-type and mutant p53, and has a RNase H-dependent mechanism of action

cenersen

Optionally, Dexamethasone 20 mg po weekly can be added after week 16 if stable disease but no HI is observed.

Rami Komrokji, MD

The purpose of the study is to test the safety of six cycles of cenersen treatment and to begin to test the hypothesis that intermittent administration of cenersen may lead to a reduced dependence on transfusion.

The study is a nonrandomized open-label treatment with varying doses of cenersen by intravenous administration to:

Primary

\*To assess the safety profile and dose limiting toxicities (DLT) of cenersen for each of three increasing dose levels as stipulated by the protocol in patients with lower risk MDS defined as low or intermediate-1 risk by IPSS.

Secondary

* To determine the lowest pharmacologically active exposure from among three increasing dose levels as stipulated by the protocol that exhibits the desired activity on erythropoiesis after evaluation of all dose levels, and
* To determine if intermittent treatment with cenersen will reduce transfusion requirements for patients with lower risk MDS.

A Study of Aezea® (Cenersen) in Transfusion Dependent Anemia Associated With Myelodysplastic Syndrome (MDS)

A Study of Aezea® (Cenersen) in Transfusion Dependent Anemia Associated With Myelodysplastic Syndrome

Assessment of adverse events for each dosing level

Erythroid Response (HI-E) from the lowest pharmacologically active exposure after evaluation of all dose levels - Reduction in RBC transfusions by greater than or equal to 4 units/8 weeks triggered by a hemoglobin transfusion threshold lower than 9 g/dL when compared to the 8 week baseline for transfusion-dependent patients (where transfusion dependence is defined as 4 units or more RBCs in 8 weeks)

Hematologic Improvement by Hb increase by ≥ 1.5 g/dL or more for at least 8 weeks and the patient is not transfusion-dependent.

H. Lee Moffitt Cancer Center and Research Institute

Eleos, Inc.

Leukemia

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Idarubicin

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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

placebo

idarubicin, cytarabine

Larry J Smith, PhD

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.

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.

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

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

cenersen, idarubicin, standard dose cytarabine

cenersen, idarubicin, HDAC (high dose cytarabine)

standard of care Ara-C and High dose Ara-C

Jorge E Cortes, MD

Edward D. Ball, MD

John DiPersio, MD

Maria Baer

Jonathan Kolitz, MD, FACP

Hugo Fernandez, MD

The principal goal of this clinical trial is to assess the ability of cenersen sodium (EL625) to improve cancer responsiveness to the established AML therapeutic agent Idarubicin used alone or in combination with Cytarabine (Ara-C).

Cenersen sodium is a drug that is designed to block the effects of a protein called p53. Laboratory evidence shows that blocking p53 will make many types of cancer, including acute myelogenous leukemia (AML), more sensitive to a variety of established cancer therapeutics while making normal tissues more resistant to the toxic effects of these agents.

This clinical trial is designed to assess the ability of cenersen sodium (EL625) in combination with Idarubicin alone or with Cytarabine to either: (1) induce remissions in patients who have previously failed to go into remission in response to chemotherapy; or (2) provide patents who have relapsed after going into a chemotherapy-induced remission with a longer remission.

Cenersen sodium is one of a new class of drugs called antisense oligonucleotides (oligos). Oligos are designed to block the production of specific proteins and thereby inhibit their function. Cenersen sodium targets p53, a widely studied protein.

In cancer, p53 occurs either in the un-mutated ("normal") or mutated forms. The majority of participants in this trial are expected to have un-mutated p53. Cenersen sodium is anticipated to sensitize cancers with un-mutated p53 to most established cancer therapeutics.

p53 has a pivotal role in protecting the body from cells that have suffered genetic damage and, as a result, do not function properly. The protein first senses the level of the damage and then forces the damaged cell to respond to the damage either by repairing itself or committing suicide. In general, the greater the level of damage the more likely the cellular response will be suicide.

Many cancer therapeutics, including both chemotherapy and radiation, cause the types of genetic damage that activate p53 and, consequently, cause either damage repair or cellular suicide. Laboratory studies suggest that cancer cells have a host of defenses that reduce the chances that these cells will respond to genetic damage by committing suicide. So compared to normal cells, cancer cells are more likely to repair the damage caused by cancer therapeutics while normal cells are more likely to commit suicide. Thus, blocking un-mutated p53 is more likely to prevent repair in cancer cells while preventing suicide in normal cells. This provides the basis for a differential effect of cenersen sodium on cancer cells verses normal cells.

When p53-dependent repair is prevented in cancer cells they begin to copy their damaged genetic information in preparation for cell division. This copying of the genetic damage triggers a p53-independent backup suicide mechanism and, as a result, the cancer cells are eliminated. This is the presumed mechanism whereby cenersen sodium is able to sensitize cancer cells with normal p53 function to numerous cancer therapeutics.

At higher doses however, chemotherapy sometimes blocks cells from copying their genes in preparation for division. Thus, it is possible that a chemotherapeutic agent used at a high dose could block any sensitizing effect that cenersen sodium might otherwise have on the cancer.

The chemotherapeutic agent Idarubicin is known to produce the type of genetic damage that effects p53 expression, causes p53-dependent responses and has been shown to be made more effective at killing cancer cells by cenersen sodium. Cytarabine (Ara-C) is the most widely used chemotherapeutic agent for AML. Cenersen sodium does not appear to sensitize cancer cells to Cytarabine and at higher doses Cytarabine may reduce the capacity of cenersen sodium to sensitize cancer cells.

Hence, this AML study will examine the effects of Cenersen sodium used in combination with Idarubicin and one of three different doses of Cytarabine (i.e. 0, 0.1 and 1.0 gm/m2/day), on the responsiveness of participants to these chemotherapeutic agents.

Dosing Study of Ara-C/EL625/Idarubicin in Refractory and Relapsed AML

Open Label, Phase II Dosing Study of Ara-C Chemotherapy in Combination With EL625 and Idarubicin in Refractory and Relapsed Acute Myelogenous Leukemia (AML)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Aezea® (Cenersen) in Transfusion Dependent Anemia Associated With Myelodysplastic Syndrome (MDS)	NCT02243124	Myelodysplastic...	cenersen Dexamethasone	18 Years - 95 Years	Eleos, Inc.
Aezea® (Cenersen) and Chemotherapy for AML Subjects ≥ 55 Years of Age With No Response to Frontline Induction Course	NCT00967512	Acute Myelogeno...	cenersen placebo idarubicin, cyt...	55 Years -	Eleos, Inc.
Dosing Study of Ara-C/EL625/Idarubicin in Refractory and Relapsed AML	NCT00074737	Acute Myelogeno...	cenersen Idarubicin Cytarabine	18 Years -	Eleos, Inc.
Dosing Study of Ara-C/EL625/Idarubicin in Refractory and Relapsed AML	NCT00074737	Acute Myelogeno...	cenersen Idarubicin Cytarabine	18 Years -	Eleos, Inc.

Spots Global Cancer Trial Database for cenersen

Every month we try and update this database with for cenersen cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for cenersen

Every month we try and update this database with for cenersen cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for cenersen cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.