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

This study has been completed.
Sponsor:
Information provided by:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00620321
First received: February 4, 2008
Last updated: October 25, 2010
Last verified: October 2010
  Purpose

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 AML.


Condition Intervention Phase
Acute Myeloid Leukemia
Drug: LY2181308 sodium
Drug: cytarabine
Drug: idarubicin
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • To understand the safety profile of LY2181308 sodium administered in combination with idarubicin and cytarabine through adverse events and serious adverse events [ Time Frame: during treatment and follow up ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Explore the activity of LY2181308 sodium in combination with idarubicin and cytarabine using remission rates and relapse-free survival. [ Time Frame: Baseline to progression ] [ Designated as safety issue: No ]
  • Refine the current LY2181308 PK/PD model using the LY2181308 PK/PD (flow cytometry) data. [ Time Frame: baseline, during study, and follow up visit ] [ Designated as safety issue: No ]
  • Explore other potential PK/PD relationships (for example, with blast counts) [ Time Frame: Baseline, during study and follow up visit ] [ Designated as safety issue: No ]
  • Explore consequences of survivin target knockdown on AML blast proliferation and blast survival by fluorescence activated cell sorting (FACS) using cell cycle progression and apoptosis markers. [ Time Frame: Baseline, during study and follow up visit ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: March 2008
Study Completion Date: January 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LY2181308 sodium, idarubicin, cytarabine Drug: LY2181308 sodium
750 mg is administered as a 3 hour intravenous (IV) infusion on Days 1, 2, 3, 8, 15, 22 of Cycle 1 and Days 1, 8, 15, 22 of Cycle 2 until disease progression or unacceptable toxicity develops.
Drug: cytarabine
1.5g/m2 will be administered as a 4 hour IV infusion on Days 3, 4, 5 of Cycle 1 and Days 1, 2, 3 of Cycle 2 until disease progression or unacceptable toxicity develops.
Drug: idarubicin
12mg/m2 will be administered as a 30 minute IV infusion on Days 3, 4, 5 of Cycle 1 and on Days 1, 2, 3 of Cycle 2 until disease progression or unacceptable toxicity develops.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients who have a diagnosis of acute myeloid leukemia that is relapsed or refractory to a 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. 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 anthra- cyclines, 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 120mg/m2).
  • Patients with a second malignancy that could affect the interpretation of the results.
  • Patients with leukemic involvement of the 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00620321

Locations
United States, Michigan
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.
Ann Arbor, Michigan, United States, 48105
United States, Texas
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.
Houston, Texas, United States, 77030
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: 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) Eli Lilly and Company
  More Information

Additional Information:
No publications provided

Responsible Party: Chief Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier: NCT00620321     History of Changes
Other Study ID Numbers: 11631, H8Z-MC-JACU
Study First Received: February 4, 2008
Last Updated: October 25, 2010
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Idarubicin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014