Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Cohort 1: 40 milligrams (mg) LY2090314 administered on Days 1, 8, and 15 of a 28-day cycle for at least two (2) 28-day cycles. Participants experiencing clinical benefit may continue treatment until after the discontinuation criteria are met.

Due to a protocol amendment on September 2010, the study added 2 additional treatment schedules/cohorts. Cohort 2: 40 mg dose given on Days 1, 5, and 9 of a 21-day cycle. Cohort 3: 40 mg dose given on Days 1, 5, 9, and 12 of a 21-day cycle. Participants experiencing clinical benefit may continue treatment until after the discontinuation criteria are met.

LY2090314

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

This study is a multicenter, non-randomized, open-label, Phase 2 study of intravenous LY2090314 in participants with acute leukemia.

A Study in Participants With Acute Leukemia

A Phase 2 Study of LY2090314 in Participants With Acute Leukemia

Drug-related events were defined as treatment-emergent serious and other non-serious AEs that were considered by the investigator to be related to study drug. A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.

The Revised International Working Group criteria were used to determine the response for participants with acute myelogenous leukemia (AML). Complete response, also known as complete remission (CR) included the following categories: Morphologic CR defined as \<5% blasts in an aspirate sample with marrow spicules and with a count of at least 200 nucleated cells, along with peripheral blood levels including platelets ≥100\*10\^9/Liter (L) and absolute neutrophil count (ANC) ≥1\*10\^9/L, Morphologic CR with incomplete blood count recovery (CRi), Cytogenetic CR, and Molecular CR. Partial response, also known as partial remission (PR) was defined as a decrease of at least 50% in blast count on the bone marrow aspirate. PR required all of the hematologic values for a CR but with a decrease of at least 50% in the percentage of blasts to 5% to 25% in the bone marrow aspirate.

The Revised International Working Group criteria were used to determine the response for participants with AML. Complete response, also known as complete remission (CR) included the following categories: Morphologic CR defined as \<5% blasts in an aspirate sample with marrow spicules and with a count of at least 200 nucleated cells, along with peripheral blood levels including platelets ≥100\*10\^9/L and ANC ≥1\*10\^9/L, Morphologic CR with incomplete blood count recovery (CRi), Cytogenetic CR, and Molecular CR. Partial response, also known as partial remission (PR) was defined as a decrease of at least 50% in blast count on the bone marrow aspirate. PR required all of the hematologic values for a CR but with a decrease of at least 50% in the percentage of blasts to 5% to 25% in the bone marrow aspirate. Percentage of participants=\[(number of participants with CR or PR)/(number of participants treated)\]\*100.

AUC(0-8) was estimated from the plasma drug concentration time profile.

AUC(0-inf) was estimated from the plasma drug concentration time profile.

Cmax is the maximum observed concentration estimated from the plasma drug concentration time profile.

Percent change=\[(β-catenin level postdose-predose level)/(predose β-catenin levels)\]\*100. Participants in Cohort 1 had β-catenin samples collected on Cycle 1: D1, D8, and D15, and Cycles 2 through 9: D1. Participants in Cohort 2 had β-catenin samples collected on Cycle 1: D1, D5, and D9 and Cycles 2 through 9: D1. Participants in Cohort 3 had β-catenin samples collected on Cycle 1: D1, D5, D9, and D12 and Cycles 2 through 9: D1.

The number of participants who died while on study treatment and the number of participants who died during the 30-day follow-up (30 days post last dose) are reported.

Eli Lilly and Company

LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D8, and D15 for two 28-day cycles.

If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met.

Cohort 1, 40 mg LY2090314: D1, D8, D15

LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, and D9 for two 21-day cycles.

If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met.

Cohort 2, 40 mg LY2090314: D1, D5, D9

LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, D9, and D12 for two 21-day cycles.

If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met.

Cohort 3, 40 mg LY2090314: D1, D5, D9, D12

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

All participants who received at least 1 dose of LY2090314.

An interim data review was performed after 6 participants in the safety lead-in completed 1 cycle of therapy. Based on the interim safety results, the expansion cohort was not opened to enrollment.

Chief Medical Officer

Study Drug-Related AE(s)

Study Drug-Related SAE(s)

Participants who received at least 1 dose of study drug.

Number of Participants With 1 or More Study Drug-Related Adverse Events (AEs) or Any Serious AEs (SAEs)

Number of Participants With Best Response of Complete Response or Partial Response

Percentage of Participants With Best Response of Complete Response or Partial Response

All participants who received at least 1 dose of LY2090314 regardless of the cohort to which they were enrolled.

Cohort 1: LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D8, and D15 for two 28-day cycles.

Cohort 2: LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, and D9 for two 21-day cycles.

Cohort 3: LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, D9, and D12 for two 21-day cycles.

If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met.

Entire Study Population

Participants who received at least 1 dose of study drug and had sufficient postdose samples collected to allow estimation of the PK parameters using noncompartmental methods of analysis.

Pharmacokinetics (PK): Area Under the Concentration-Time Curve From Time 0 to 8 Hours (h) Postdose [AUC(0-8)]

PK: AUC From Time 0 to Infinity [AUC(0-inf)]

PK: Maximum Concentration (Cmax)

Cycle 1, Day 1, 1 h postdose

Cycle 1, Day 1, 2 h postdose

Cycle 1, Day 1, 4 h postdose

Cycle 1, Day 1, 8 h postdose

Cycle 1, Day 1, 24 h postdose

Cycle 1, Day 5, 2 h postdose

Cycle 1, Day 8, 2 h postdose

Cycle 1, Day 9, 1 h postdose

Cycle 1, Day 9, 2 h postdose

Cycle 1, Day 9, 4 h postdose

Cycle 1, Day 9, 8 h postdose

Cycle 1, Day 9, 24 h postdose

Cycle 1, Day 12, 2 h postdose

Cycle 1, Day 15, 1 h postdose

Cycle 1, Day 15, 2 h postdose

Cycle 1, Day 15, 4 h postdose

Cycle 1, Day 15, 8 h postdose

Cycle 2, Day 1, 2 h postdose

Cycle 3, Day 1, 2 h postdose

Cycle 4, Day 1, 2 h postdose

Cycle 5, Day 1, 2 h postdose

Cycle 6, Day 1, 2 h postdose

Cycle 7, Day 1, 2 h postdose

Cycle 8, Day 1, 2 h postdose

Cycle 9, Day 1, 2 h postdose

Participants who received at least 1 dose of study drug and had a predose and at least 1 postdose β-catenin sample collected.

Percent Change From Predose Beta (β)-Catenin Levels

Death On Study, Prior To Cycle 2 Completion

Death On Study, Post Cycle 2 Completion

Death During 30-Day Follow-Up

Number of Participants Who Died

LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on Day (D)1, D8, and D15 for two 28-day cycles.

If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met.

Overall Study

Digestive System Diseases

Gland and Hormone Related Diseases

Symptoms and General Pathology

Pancreatic Neoplasms

Neoplasm Metastasis

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Vitamins

Gemcitabine

Paclitaxel

Albumin-Bound Paclitaxel

Oxaliplatin

Leucovorin

Fluorouracil

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Antidotes

Protective Agents

Folic Acid

Vitamin B Complex

Trace Elements

Folate

Vitamin B9

LY2090314 given intravenously (IV) on days 1 (at cycle 1 LY2090314 given on day 0 instead of day 1), 8 and 15 in 28 day cycle in combination with 1000 milligram/square meter (mg/m\^2) gemcitabine given IV on days 1, 8 and 15. Cohort closed to new enrollment per protocol addendum.

LY2090314 given IV on days 1 (at cycle 1 LY2090314 given on day 0 instead of day 1), and 15 in 28 day cycle in combination with FOLFOX (leucovorin + 5-fluorouracil + oxaliplatin) given IV, on days 1 and 15 in 28 day cycle.

LY2090314 given IV on days 1 (at cycle 1 LY2090314 given on day 0 instead of day 1), 8 and 15 in 28 day cycle in combination with 1000 mg/m\^2 gemcitabine + 125 mg/m\^2 nab-paclitaxel given IV on days 1, 8 and 15 in 28-day cycle. New cohort opened per protocol amendment.

FOLFOX

Nab-paclitaxel

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)

Purpose of this phase I/II study is to test how well LY2090314 works in combination with different chemotherapies in treating participants with metastatic pancreatic cancer.

A Study of LY2090314 and Chemotherapy in Participants With Metastatic Pancreatic Cancer

Phase I/II Study of LY2090314 and Chemotherapy in Metastatic Pancreatic Cancer Patients With Metastases Amenable to Biopsy

Change in the phosphorylation level of glycogen synthase, a glycogen synthase kinase-3 beta (GSK-3beta) inhibitor, from baseline to 4 hours post-treatment on day 0 using tumor tissue and blood specimens.

PFS was as the time from enrollment to the earliest documented evidence of disease progression or death,whatever comes first.

Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST v1.1) criteria. CR was defined as the disappearance of all target and non-target lesions and all target and non-target lymph nodes were non-pathological or normal in size \[\<10 millimeter (mm) short axis\]. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions taking as reference the baseline sum diameters. ORR calculated as: (sum of the number of participants with PRs and CRs) divided by (number of evaluable participants) multiplied by 100.

A CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart.

Mayo Clinic

All participants who received at least one dose of study drug.

LY2090314 given intravenously (IV) on days 1 (at cycle 1 LY2090314 given on day 0 instead of day 1), 8 and 15 in 28 day cycle in combination with 1000 milligram/square meter (mg/m²) gemcitabine given IV on days 1, 8 and 15. Cohort closed to new enrollment per protocol addendum.

LY2090314 + Gemcitabine

LY2090314 + FOLFOX

Study was terminated due to slow enrollment. No participants were enrolled in arm LY2090314 + Gemcitabine + Nab-paclitaxel due to inability to enroll participants.

Zero participants analyzed. GSK3β phosphorylation levels were not determined, and the primary endpoint was not examined as there wasn't viable tumor tissue for analysis.

Change From Baseline to 4 Hours Post-Treatment on Day 0 in Glycogen Synthase Phosphorylation

All the participants that received at least one dose of study drug.

Overall Survival (OS)

Percentage of Participants Who Survived at 6 Months

Progression Free Survival (PFS)

Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Overall Response Rate (ORR)]

LY2090314 given IV on days 1 (at cycle 1 LY2090314 given on day 0 instead of day 1), 8 and 15 in 28 day cycle in combination with 1000 mg/m² gemcitabine + 125 mg/m² nab-paclitaxel given IV on days 1, 8 and 15 in 28-day cycle. New cohort opened per protocol amendment.

LY2090314 + Gemcitabine + Nab-paclitaxel

Neoplastic Processes

Gastrointestinal Agents

Anticoagulants

Anti-Infective Agents

Other Dietary Supplements

Carboplatin

Pemetrexed

Ranitidine

Ranitidine bismuth citrate

Bismuth

Citric Acid

Sodium Citrate

Bismuth tripotassium dicitrate

Enzyme Inhibitors

Folic Acid Antagonists

Antacids

Anti-Ulcer Agents

Histamine

Histamine H2 Antagonists

Histamine phosphate

Histamine Antagonists

Neurotransmitter Agents

Citrate

Folinic Acid

Part A, Cycle 1 (28 days): Intravenous doses of LY2090314 starting at 10 milligram (mg) were given on Day 1 followed by 10 mg LY2090314, 500 milligram per square meter (mg/m\^2) pemetrexed (intravenous dose), and 5 or 6 area under the concentration-time curve (AUC) intravenous dose of carboplatin on Day 8.

Part A, Cycle 2 (21 days): Pemetrexed and carboplatin given on Day 1 at the same dose administered in Cycle 1.

Part A, Cycle 3 (21 days) and beyond: LY2090314, Pemetrexed and carboplatin were given on Day 1 at the same dose administered in Cycle 1. LY2090314 doses were escalated until the maximum tolerated dose (MTD) was reached.

Part B: Dose determined in Part A was administered. Participants were allowed to continue the combination treatment if they were receiving therapeutic benefit until they fulfilled one of the criteria for discontinuation.

pemetrexed

Per I2H-MC-JWYA Protocol Amendment (d) approved 11 March 2010, 50 mg ranitidine given as pretreatment to LY2090314 for stomach pain.

ranitidine

The purpose of this study is to determine a recommended Phase 2 dose and dosing regimen of LY2090314 in combination with pemetrexed and carboplatin in patients with advanced/metastatic cancer. Part A of this study will consist of dose escalation of the study regimen, and Part B will consist of an expanded cohort to confirm the dose provided from Part A.

A Study of LY2090314 in Patients With Advanced or Metastatic Cancer

Phase 1 Dose Escalation Study of LY2090314 in Patients With Advanced or Metastatic Cancer in Combination With Pemetrexed and Carboplatin

Recommended Phase 2 MTD was determined, when a dose limiting toxicity (DLT) occurred in 1 of 3 participants, the cohort was to be expanded to 6 participants. If a DLT occurred in 2 or more participants, accrual to the cohort was stopped, as the MTD was exceeded. A DLT was defined as an adverse event (AE) occurring in Cycle 1 (28 days) that was possibly related to study drug and met 1 of the following criteria: According to the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0, ≥Grade 3 nonhematologic toxicity (except for nausea/vomiting without maximal symptomatic/prophylactic treatment) possibly or likely related to the study medication;CTCAE Grade 4 hematological toxicity of \>5 days duration; Febrile neutropenia; CTCAE Grade 4 thrombocytopenia; CTCAE ≥Grade 2 thrombocytopenia plus bleeding; CTCAE ≥Grade 3 prolonged QTc interval.

AUC0-∞ was calculated from the area under the concentration versus time curve from time 0 to infinity of LY2090314 when administered alone.

AUC0-∞ was calculated from the area under the concentration versus time curves of LY2090314 from time zero to infinity when coadministered with Pem and Carb.

Best overall observed tumor response at any point during the study until disease progression/recurrence defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response (CR) was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter (mm) and normalization of tumor marker level of non-target lesions; Partial Response (PR) was defined as at least 30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD) was defined as at least 20% increase in sum of longest diameter of target lesions and minimum 5 mm increase over nadir; Stable Disease (SD) was defined as small changes that did not meet above criteria.

AUC0-∞ was calculated from the area under the concentration versus time curves of Pem given as a single dose with Carb (doublet therapy) and when co-administered with Carb and LY2090314 (triplet therapy).

Cmax of Pem given as a single dose with Carb (doublet therapy) and when coadministered with Carb and LY2090314 (triplet therapy).

AUC0-∞ of free Carb was calculated from the area under the concentration versus time curves of Carb given as a single dose with Pem (doublet therapy) and when co-administered with Pem and LY2090314 (triplet therapy).

Cmax of free Carb given as a single dose with Pem (doublet therapy) and when co-administered with Pem and LY2090314 (triplet therapy).

PD change from baseline to endpoint (up to Cycle 9) in β-catenin levels in peripheral blood mononuclear cells (PBMCs) following the administration of LY2090314 given alone and in combination with Pem and Carb. This outcome measure was not analyzed due to insufficient data.

* Cycle 1 Day 1 of 28 day cycle: 10 mg LY2090314 administered by intravenous infusion.
* Cycle 1 Day 8 of 28 day cycle: 500 mg/m\^2 Pem administered by intravenous infusion followed by AUC 5 mg/mL \* min Carb administered by intravenous infusion.
* Cycle 2 up to Cycle 9: Day 1 of 21 day cycle: 500 mg/m\^2 Pem administered by intravenous infusion followed by AUC 5 mg/mL \* min Carb administered by intravenous infusion followed by 10 mg LY2090314 administered by intravenous infusion.

LY 10/Carb 5/Pem 500 (Cohort 1)

* Cycle 1 Day 1 of 28 day cycle: 10 mg LY2090314 by intravenous infusion.
* Cycle 1 Day 8 of 28 day cycle: 500 mg/m\^2 by Pem intravenous infusion followed by AUC 6 mg/mL \* min Carb by intravenous infusion.
* Cycle 2 up to Cycle 9: Day 1 of 21 day cycle: 500 mg/m\^2 Pem by intravenous infusion followed by AUC 6 mg/mL \* min Carb by intravenous infusion followed by 10 mg LY2090314 by intravenous infusion.

LY 10/Carb 6/Pem 500 (Cohort 2)

* Cycle 1 Day 1 of 28 day cycle: 20 mg LY2090314 by intravenous infusion.
* Cycle 1 Day 8 of 28 day cycle: 500 mg/m\^2 Pem by intravenous infusion followed by AUC 6 mg/mL \* min Carb by intravenous infusion.
* Cycle 2 up to Cycle 9: Day 1 of 21 day cycle: 500 mg/m\^2 Pem by intravenous infusion followed by AUC 6 mg/mL \* min Carb by intravenous infusion followed by 20 mg LY2090314 by intravenous infusion.

LY 20/Carb 6/Pem 500 (Cohort 3)

* Cycle 1 Day 1 of 28 day cycle: 40 mg LY2090314 by intravenous infusion.
* Cycle 1 Day 8 of 28 day cycle: 500 mg/m\^2 Pem by intravenous infusion followed by AUC 6 mg/mL \* min Carb by intravenous infusion followed by 40 mg LY2090314 by intravenous infusion.
* Cycle 2 Day 1 of 21 day cycle: AUC 6 mg/mL \* min Carb by intravenous infusion followed by 500 mg/m\^2 Pem by intravenous infusion.
* Cycle 3 up to Cycle 9: Day 1 of 21 day cycle: 500 mg/m\^2 Pem by intravenous infusion followed by AUC 6 mg/mL \* min Carb by intravenous infusion followed by 40 mg LY2090314 by intravenous infusion.

LY 40/Carb 6/Pem 500 (Cohort 4)

* Cycle 1 Day 1 of 28 day cycle: 80 mg LY2090314 by intravenous infusion.
* Cycle 1 Day 8 of 28 day cycle: 500 mg/m\^2 Pem by intravenous infusion followed by AUC 6 mg/mL \* min Carb by intravenous infusion followed by 80 mg LY2090314 by intravenous infusion.
* Cycle 2 Day 1 of 21 day cycle: AUC 6 mg/mL \* min Carb by intravenous infusion followed by 500 mg/m\^2 Pem by intravenous infusion.
* Cycle 3 up to Cycle 9: Day 1 of 21 day cycle: 500 mg/m\^2 Pem by intravenous infusion followed by AUC 6 mg/mL \* min Carb by intravenous infusion followed by 80 mg LY2090314 by intravenous infusion.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study in Participants With Acute Leukemia	NCT01214603	Leukemia	LY2090314	18 Years -	Eli Lilly and Company
A Study of LY2090314 and Chemotherapy in Participants With Metastatic Pancreatic Cancer	NCT01632306	Pancreatic Canc...	LY2090314 FOLFOX Gemcitabine Nab-paclitaxel	18 Years -	Eli Lilly and Company
A Study of LY2090314 in Patients With Advanced or Metastatic Cancer	NCT01287520	Advanced Cancer	LY2090314 pemetrexed Carboplatin ranitidine	25 Years -	Eli Lilly and Company

Spots Global Cancer Trial Database for ly2090314

Every month we try and update this database with for ly2090314 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 ly2090314

Every month we try and update this database with for ly2090314 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 ly2090314 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.