Clinical trial NCT00620321: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2008-02-21
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Number of Participants With Adverse Events (Safety Profile)
timeFrame: Start of treatment to study completion up to 6.7 months
Secondary outcomes:
measure: Percentage of Participants With Response to LY2181308 Sodium in Combination With Idarubicin and Cytarabine (Remission Rates)
timeFrame: Baseline to progression of disease or death up to 6 months
measure: Relapse-Free Survival
timeFrame: Baseline to progression of disease or death up to 6 months
measure: Area Under the Curve of LY2181308 Over the Dosing Interval
timeFrame: Day 3: 0,12,24,36,48,60,72,84,96,108,120,132 hours
measure: Pharmacodynamics: Number of Participants With Survivin Protein Expression
timeFrame: 6 Months
measure: Change From Baseline in Survivin Index at Day 2
timeFrame: Baseline, Day 2
Other outcomes:
measure: Number of Participants Who Died Due to Progressive Disease or Unknown Cause During the 21 Days Post Study Treatment Follow-Up
timeFrame: Study treatment discontinuation up to 21 days post study treatment discontinuation
Locations:
city: Ann Arbor
country: United States
facility: 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.
state: Michigan
city: Houston
country: United States
facility: 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.
state: Texas
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References:
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.