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Study Summary
No. 2007-0707:.......Leukemia......Michael Andreeff......Stem Cell Transplantation and Cellular Therapy
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Study Summary Title
Study Summary
Number:
2007-0707
Study 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
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Physician New Patient Referral
Name:Michael AndreeffPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Stem Cell Transplantation and Cellular TherapyReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-7260
Contact us about clinical trials
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General Information
Disease Group:LeukemiaSupported By:Eli Lilly and Company
Phase of Study:Phase IIReturn
Visit:
Weekly minimally. During the first 15 days there are frequent research lab
draws.
Treatment
Agents:
4-Demethoxydaunorubicin
Cytarabine
LY2181308 Sodium
Home Care:Supportive care such as prophylactic antimicrobial coverage, medications for
minor adverse events such as diarrhea, constipation, or nausea.
Treatment Loc:Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions
Estimated
Length of Stay
in Houston:
Hospitalization is not required for infusion days only unless a neutropenic
fever or other side effect develops.
Description/
Intervention:
The goal of this clinical research study is to learn if LY2181308 sodium in
combination with idarubicin and cytarabine can help to control the disease in
patients with refractory or relapsed acute myeloid leukemia. The safety of this
drug in combination with idarubicin and cytarabine will also be studied.
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Study Objectives / Outcomes
Primary Objective

    The primary objective of this JACU(c) amendment is to understand the safety profile of LY2181308 sodium administered in combination with idarubicin and cytarabine to patients with relapsed or refractory AML. The primary objective pre-amendment JACU(c) was to establish proof-of-concept of survivin knockdown in AML blast cells in vivo when LY2181308 sodium is administered to patients with relapsed or refractory AML.

Secondary Objectives
  • Explore the activity of LY2181308 sodium in combination with idarubicin and cytarabine in relapsed or refractory AML using remission rates and relapse-free-survival.
  • Refine the current LY2181308 sodium PK/PD model using the LY2181308 sodium pharmacokinetic and pharmacodynamic (flow cytometry) data and explore other potential PK/PD relationships (for example, with the blast count).
  • Explore the consequences of survivin target modulation (knockdown) on AML blast proliferation and survival by fluorescence activated cell sorting (FACS) using cell cycle progression and apoptosis markers.
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Study Status Information
Study Activation / Registration Date:
IRB Review and Approval Date:07/18/2008
Study Type:Phase Ii Or Phase I/Ii
Recruitment Status:Open
Projected Accrual:20
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) 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 (TKI). A baseline bone marrow assessment is required </= 96 hours prior to the first dose of study drug. The results of this bone marrow assessment do not need to be known prior to the first dose of study drug.

2) Have a performance status of 0 to 2 on the Eastern Cooperative Oncology Group (ECOG) scale

3) 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) . . .

4) . . . 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.

5) Have given written informed consent approved by Lilly and the ethical review board (ERB)/institutional review board (IRB) governing the site.

6) Female patients of child-bearing potential must have a negative serum pregnancy test within 96 hours of enrollment. 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.

7) Exhibit patient compliance and geographic proximity that allow for adequate follow-up.

8) Patient must be at least 18 years of age.

9) Have adequate organ function including: Hepatic: Bilirubin <=1.5 x ULN. Alkaline phosphatase and transaminases (ALT and AST) <= 5 x ULN. However, ALT and/or AST elevations > 5 x ULN may be acceptable with asymptomatic or clinically nonrelevant elevation of these isolated transaminases. For example, elevation of transaminases may be secondary to heart or muscle disease (elevation of AST) or inflammatory reactions affecting the liver (elevation of ALT) that is not indicative of severe hepatic impairment or hepatic metastases. (continued)

10) In addition, combined AST and ALT without increases in bilirubin may be observed in patients experiencing hemolysis. In cases where elevations of AST, ALT, and/or bilirubin are noted at baseline, the patient may enter treatment as long as there is evidence that the laboratory elevations of the liver-related enzymes are not a reflection of severe hepatic impairment. Renal: Serum creatinine <= ULN. No known active renal disease. In rare cases, patients may enter treatment with a serum creatinine > ULN as elevations of serum creatinine may be secondary to dehydration. (continued)

11) This requires prior approval by the Lilly physician and must be consistent with the patient's history.

Exclusion Criteria:1) Have received treatment 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.

2) Have previously completed or withdrawn from this study or any other study investigation LY2181308 sodium.

3) Patients with M3 AML, APML (acute promyelocytic leukemia).

4) Known hypersensitivity to oligonucleotides or any component of the formulation.

5) Patients with leukemic involvement of the CNS by spinal fluid cytology or imaging. Patients with signs or symptoms of leukemic meningitis or a history of leukemic meningitis must have a negative lumbar puncture within 2 weeks of study enrollment.

6) Patients with serious concomitant disorders, including active bacterial, fungal, or viral infection, incompatible with the study (at the discretion of the investigator).

7) Patients with a second primary malignancy that could affect interpretation of the results.

8) Patients with serious preexisting medical conditions (at the investigator's discretion). Because of the known cardiac toxicity of anthracyclines, patients with preexisting ejection fraction (EF) </=45% should not participate in this study. No patient should exceed the maximum exposure of anthracycline doses (for example, idarubicin greater than 120 mg/meter sq).

9) Patients with a known coagulopathy or bleeding disorder, other than leukemia-related thrombocytopenia. Patients with severe or life-threatening bleeding refractory to platelet transfusion are also excluded from this study.

10) Major surgery within 4 weeks of study enrollment.

11) Concomitant anticoagulant therapy (with the exception of the use of heparinized saline to maintain the patency of central venous catheters).

12) Presence of clinical evidence of viral disease caused by human immunodeficiency virus (HIV), hepatitis B, or hepatitis C antibodies (HCAb). A serum positive result for presence of surface antigen-antibodies (HBSag) or antibodies to HCV (HCAb) alone does not constitute an exclusion. As required by standard medical practice, active viral disease must be determined to exclude such patients.

13) Women who become pregnant or are lactating.

14) Patients with a known hypersensitivity to idarubicin and/or cytarabine.

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Links
Registration Number: NCT00620321
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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