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A Study of LY2181308 Sodium in Patients With Relapsed or Refractory Acute Myeloid Leukemia

Primary Purpose

Acute Myeloid Leukemia

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

LY2181308 sodium

cytarabine

idarubicin

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients who have a diagnosis of acute myeloid leukemia that is relapsed or refractory to at least 1 prior treatment for leukemia, or patients with chronic myeloid leukemia (CML) who are in myeloid blast crisis which have failed at least 1 previous tyrosine kinase inhibitor (TK1). A baseline bone marrow assessment is required less than or equal to 96 hours prior to the first dose of study drug.
Must have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, immunotherapy, cancer related hormone therapy, or other investigational therapy for at least 21 days for myelosuppressive agents (such as cytarabine, daunorubicin, and gemtuzumab ozogamicin) or 14 days for non-myelosuppressive agents prior to receiving study drug, and recovered from the acute effects of therapy (such as neurotoxicity, diarrhea, and mucositis) except for residual myelosuppression and alopecia. Hydroxyurea is permitted to control the peripheral blast cell count, but must be stopped at least 24 hours before study drug administration.
Must have adequate organ function.
Females must have a negative pregnancy test. Male and female patients must agree to use a reliable method of birth control during and for 6 months following the last dose of study drug.
Patients must be at least 18 years old.

Exclusion Criteria:

Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication within 14 or 21 days of the initial dose of study drug for a non-myelosuppressive or myelosuppressive agent, respectively.
Patients with acute promyelocytic leukemia (APML).
Major surgery within 4 weeks of study enrollment.
Patients with serious pre-existing medical conditions (at the discretion of the investigator). Because of the known cardiac toxicity of anthracyclines, patients with pre-existing ejection fraction (EF) less than or equal to 45% should not participate in this study. No patient should exceed the maximum exposure of anthracycline doses (for example, idarubicin greater than 120 mg/m²).
Patients with a second malignancy that could affect the interpretation of the results.
Patients with leukemic involvement of the central nervous system (CNS) by spinal fluid cytology or imaging.
Patients with known coagulopathy or bleeding disorder, other than leukemia related thrombocytopenia. Patients with severe of life threatening bleeding refractory to platelet transfusions are also excluded.
Concomitant anticoagulant therapy (with the exception of heparinized saline to maintain the patency of central venous catheters).
Women who are pregnant or breast feeding.
Patients with a known hypersensitivity to oligonucleotides, idarubicin, and/or cytarabine.

Sites / Locations

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

LY2181308 sodium, idarubicin, cytarabine

Arm Description

Outcomes

Primary Outcome Measures

Number of Participants With Adverse Events (Safety Profile)

Data are presented as number of participants who experienced serious adverse events (SAE) and possibly drug-related treatment-emergent adverse events (TEAE) during the study including the 21-day follow-up period. A summary of serious adverse events and other nonserious adverse events regardless of causality is located in the Reported Adverse Events section.

Secondary Outcome Measures

Percentage of Participants With Response to LY2181308 Sodium in Combination With Idarubicin and Cytarabine (Remission Rates)

Response is complete remission (CR) + CR with incomplete blood count recovery (CRi) + partial remission (PR) + cytoreduction. CR: fewer than 5% blasts based on a cell count of at least 200 cells from a bone marrow aspirate containing bone marrow spicules, in the setting of peripheral blood recovery to: platelets ≥100x10⁹/liter (L), neutrophils ≥10⁹/L. PR: defined as a decrease of at least 50% in blast count on the bone marrow aspirate; or cytoreduction (defined as a decrease in blast count not meeting the criteria for a PR or CR). Response rate is calculated as a total number of participants with CR or CRi or PR or cytoreduction divided by the total number of participants treated multiplied by 100.

Relapse-Free Survival

Relapse-Free Survival was defined as the time from first objective status assessment of complete remission (CR) or CR with incomplete blood count recovery (CRi) or partial remission (PR) or cytoreduction to the first time of disease progression or death as a result of any cause. CR: fewer than 5% blasts based on a cell count of at least 200 cells from a bone marrow aspirate containing bone marrow spicules, in the setting of peripheral blood recovery to: platelets ≥100x10⁹/liter (L), neutrophils ≥10⁹/L. PR: defined as a decrease of at least 50% in blast count on the bone marrow aspirate; or cytoreduction (defined as a decrease in blast count not meeting the criteria for a PR or CR). There were too few participants who had a documented progression of disease or death event amongst the participants with a response of CR, CRi, PR or cytoreduction to conduct the time-to-event analysis, thus the relapse-free survival was not analyzed.

Area Under the Curve of LY2181308 Over the Dosing Interval

Area under the curve of LY2181308 over the dosing interval

Pharmacodynamics: Number of Participants With Survivin Protein Expression

Pharmacodynamics: Number of participants with Survivin Protein Expression.

Change From Baseline in Survivin Index at Day 2

Data presented are the ratio of Day 2 survivin index to the baseline survivin index. Survivin is a protein expressed in tumor cells, including acute myeloid leukemia (AML), which regulates mitosis and prevents tumor cell death. Survivin index was calculated as ([blast survivin mean equivalent fluorochrome (MEFL) - blast isotypic control MEFL]/blast isotypic control MEFL).

Full Information

NCT ID

NCT00620321

First Posted

February 4, 2008

Last Updated

August 26, 2019

Sponsor

Eli Lilly and Company

1. Study Identification

Unique Protocol Identification Number

NCT00620321

Brief Title

A Study of LY2181308 Sodium in Patients With Relapsed or Refractory Acute Myeloid Leukemia

Official Title

An Open-Label Phase 2 Trial of LY2181308 Sodium Administered in Combination With Idarubicin and Cytarabine to Patients With Refractory or Relapsed Acute Myeloid Leukemia

Study Type

Interventional

2. Study Status

Record Verification Date

August 2019

Overall Recruitment Status

Completed

Study Start Date

March 2008 (undefined)

Primary Completion Date

January 2010 (Actual)

Study Completion Date

January 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eli Lilly and Company

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study is to understand the safety profile of LY2181308 sodium administered in combination with idarubicin and cytarabine to patients with relapsed or refractory acute myeloid leukemia (AML).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Myeloid Leukemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

LY2181308 sodium, idarubicin, cytarabine

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

LY2181308 sodium

Intervention Description

750 milligrams (mg) is administered as a 3-hour intravenous infusion on Days 1, 2, 3, 8, 15, 22 of Cycle 1 (28 days) and Days 1, 8, 15, 22 of Cycle 2 (28 days) until disease progression or unacceptable toxicity develops.

Intervention Type

Drug

Intervention Name(s)

cytarabine

Intervention Description

1.5 grams per square meter (g/m²) will be administered as a 4-hour intravenous infusion on Days 3, 4, 5 of Cycle 1 (28 days) and Days 1, 2, 3 of Cycle 2 (28 days) until disease progression or unacceptable toxicity develops.

Intervention Type

Drug

Intervention Name(s)

idarubicin

Intervention Description

12 milligrams per square meter (mg/m²) will be administered as a 30-minute intravenous infusion on Days 3, 4, 5 of Cycle 1 (28 days) and on Days 1, 2, 3 of Cycle 2 (28 days) until disease progression or unacceptable toxicity develops.

Primary Outcome Measure Information:

Title

Number of Participants With Adverse Events (Safety Profile)

Description

Time Frame

Start of treatment to study completion up to 6.7 months

Secondary Outcome Measure Information:

Title

Percentage of Participants With Response to LY2181308 Sodium in Combination With Idarubicin and Cytarabine (Remission Rates)

Description

Time Frame

Baseline to progression of disease or death up to 6 months

Title

Relapse-Free Survival

Description

Time Frame

Baseline to progression of disease or death up to 6 months

Title

Area Under the Curve of LY2181308 Over the Dosing Interval

Description

Area under the curve of LY2181308 over the dosing interval

Time Frame

Day 3: 0,12,24,36,48,60,72,84,96,108,120,132 hours

Title

Pharmacodynamics: Number of Participants With Survivin Protein Expression

Description

Pharmacodynamics: Number of participants with Survivin Protein Expression.

Time Frame

6 Months

Title

Change From Baseline in Survivin Index at Day 2

Description

Time Frame

Baseline, Day 2

Other Pre-specified Outcome Measures:

Title

Number of Participants Who Died Due to Progressive Disease or Unknown Cause During the 21 Days Post Study Treatment Follow-Up

Description

Deaths due to progressive disease (PD) and unknown cause are not considered adverse events. Deaths due to PD and unknown cause occurring during the 21-day follow-up period after treatment discontinuation are reported here and for those occurring while participants were on treatment are reported in the Participant Flow. Deaths due to serious adverse events occurred during the study including the 21-day follow-up period are reported in the Reported Adverse Events section.

Time Frame

Study treatment discontinuation up to 21 days post study treatment discontinuation

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients who have a diagnosis of acute myeloid leukemia that is relapsed or refractory to at least 1 prior treatment for leukemia, or patients with chronic myeloid leukemia (CML) who are in myeloid blast crisis which have failed at least 1 previous tyrosine kinase inhibitor (TK1). A baseline bone marrow assessment is required less than or equal to 96 hours prior to the first dose of study drug. Must have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, immunotherapy, cancer related hormone therapy, or other investigational therapy for at least 21 days for myelosuppressive agents (such as cytarabine, daunorubicin, and gemtuzumab ozogamicin) or 14 days for non-myelosuppressive agents prior to receiving study drug, and recovered from the acute effects of therapy (such as neurotoxicity, diarrhea, and mucositis) except for residual myelosuppression and alopecia. Hydroxyurea is permitted to control the peripheral blast cell count, but must be stopped at least 24 hours before study drug administration. Must have adequate organ function. Females must have a negative pregnancy test. Male and female patients must agree to use a reliable method of birth control during and for 6 months following the last dose of study drug. Patients must be at least 18 years old. Exclusion Criteria: Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication within 14 or 21 days of the initial dose of study drug for a non-myelosuppressive or myelosuppressive agent, respectively. Patients with acute promyelocytic leukemia (APML). Major surgery within 4 weeks of study enrollment. Patients with serious pre-existing medical conditions (at the discretion of the investigator). Because of the known cardiac toxicity of anthracyclines, patients with pre-existing ejection fraction (EF) less than or equal to 45% should not participate in this study. No patient should exceed the maximum exposure of anthracycline doses (for example, idarubicin greater than 120 mg/m²). Patients with a second malignancy that could affect the interpretation of the results. Patients with leukemic involvement of the central nervous system (CNS) by spinal fluid cytology or imaging. Patients with known coagulopathy or bleeding disorder, other than leukemia related thrombocytopenia. Patients with severe of life threatening bleeding refractory to platelet transfusions are also excluded. Concomitant anticoagulant therapy (with the exception of heparinized saline to maintain the patency of central venous catheters). Women who are pregnant or breast feeding. Patients with a known hypersensitivity to oligonucleotides, idarubicin, and/or cytarabine.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT-5 hours, EST)

Organizational Affiliation

Eli Lilly and Company

Official's Role

Study Director

Facility Information:

Facility Name

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48105

Country

United States

Facility Name

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

IPD Sharing Time Frame

Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.

IPD Sharing Access Criteria

A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

IPD Sharing URL

https://vivli.org/

Citations:

PubMed Identifier

23397500

Citation

Erba HP, Sayar H, Juckett M, Lahn M, Andre V, Callies S, Schmidt S, Kadam S, Brandt JT, Van Bockstaele D, Andreeff M. Safety and pharmacokinetics of the antisense oligonucleotide (ASO) LY2181308 as a single-agent or in combination with idarubicin and cytarabine in patients with refractory or relapsed acute myeloid leukemia (AML). Invest New Drugs. 2013 Aug;31(4):1023-34. doi: 10.1007/s10637-013-9935-x. Epub 2013 Feb 10.

Results Reference

result

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A Study of LY2181308 Sodium in Patients With Relapsed or Refractory Acute Myeloid Leukemia

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