Neoplasms

Blood and Lymph Conditions

All Conditions

Heart and Blood Diseases

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Thrombocytosis

Thrombocythemia, Essential

Neoplasms by Histologic Type

Hematologic Diseases

Blood Platelet Disorders

Myeloproliferative Disorders

Bone Marrow Diseases

Hemostatic Disorders

Blood Coagulation Disorders

Hemorrhagic Disorders

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Essential Thrombocythemia

Chronic Myeloproliferative Disorders

Individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Dosing will be done on Day 1 of a 35-day cycle for acute myeloid leukemia (AML) and Day 1 of a 28-day cycle for essential thrombocythemia (ET) for at least one cycle. A participant may have additional cycles of LY573636 if he or she is receiving benefit from the study drug and does not fulfill any of the criteria for study discontinuation.

LY573636-sodium

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

The purpose of this study is to determine a safe dose of LY573636-sodium to be given to patients with acute myeloid leukemia and to determine any side effects that may be associated with LY573636-sodium in this patient population. Efficacy measures will also be used to assess the activity of LY573636-sodium in acute myeloid leukemia and essential thrombocythemia patients.

Study of LY573636-sodium in Essential Thrombocythemia and Acute Myeloid Leukemia

Phase 1 Study of LY573636-sodium in Patients With Essential Thrombocythemia and Acute Myeloid Leukemia

Recommended Phase 2 dose was determined by maximum tolerated dose (MTD). MTD is the highest dose at which no more than 1 of 6 participants experienced a dose-limiting toxicity (DLT) and level immediately below that which had ≥2 instances of DLT. A DLT is an adverse event (AE) observed during the first cycle of treatment that is believed to be related to LY573636 and fulfills any of the following: ET only , Common Terminology Criteria for AE (CTCAE, Version 3.0) Grade (Gr) 4 hematologic toxicity for ≥3 days; For all, ≥Gr 3 nonhematological toxicity except for nausea/vomiting or diarrhea unless it fits the next criteria; ≥Gr 3 nausea, vomiting, or diarrhea that persists \>7 days despite maximal treatment; Gr 3 electrolyte disturbances that persist despite maximal measures; DLT can be declared if a participant experienced increasing toxicity during treatment. The primary outcome measure was not analyzed because the enrollment was stopped early before MTD was reached.

LY573636 has been found to be highly bound to albumin. AUCalb is a surrogate measure of exposure to unbound (free) LY573636.

PK sample is withdrawn at any time on days 8,14,15,21,28.

The International Working Group's revised recommendations were used to assess response in acute myeloid leukemia (AML): complete response (CR) is \<5% blasts in BM and with a cell count ≥200 cells in BM, and with peripheral blood platelets ≥100x10⁹/liter (L) and absolute neutrophils ≥1x10⁹/L; CR with incomplete blood count recovery is defined as CRi; partial response (PR) is ≥5% blasts in BM but with ≥50% reduction in blast count. Number of responders for AML = CR+PR+ CRi. Result of a European Leukemia Net consensus conference was used to assess response in essential thrombocythemia (ET). CR is platelets ≤400x10⁹/L in peripheral blood, no disease-related symptoms, normal spleen size and white blood cells ≤10x10⁹/L in peripheral blood; PR has platelets ≤600x10⁹/L in peripheral blood or decrease \> 50% from baseline but does not meet CR criteria. Number of responders for ET = CR+PR.

PK sample is withdrawn at any time on days 8,14,15,21,28.

Eli Lilly and Company

Participants diagnosed with acute myeloid leukemia (AML) dosed: LY573636 targeting a maximum concentration (Cmax) of 250 micrograms per milliliter (μg/mL) as a 24-hour infusion on Day 1 of a 35-day cycle.

Cmax 250 μg/mL (AML)

Participants diagnosed with AML dosed: LY573636 targeting a Cmax of 300 μg/mL as a 24-hour infusion on Day 1 of a 35-day cycle.

Cmax 300 μg/mL (AML)

Participants diagnosed with AML dosed: LY573636 targeting a Cmax of 350 μg/mL as a 24-hour infusion on Day 1 of a 35-day cycle.

Cmax 350 μg/mL (AML)

Participants diagnosed with AML dosed: LY573636 targeting a Cmax of 400 μg/mL as a 24-hour infusion on Day 1 of a 35-day cycle.

Cmax 400 μg/mL (AML)

Participants diagnosed with AML dosed: LY573636 targeting an albumin-corrected exposure (AUCalb) 5500 micrograms\*hour per milliliter (µg\*hr/mL) as a 2-hour infusion on Day 1 of a 35-day cycle.

Participants diagnosed with essential thrombocythemia (ET) dosed: LY573636 targeting an AUCalb 5500 µg\*hr/mL as a 2-hour infusion on Day 1 of a 28-day cycle.

AUCalb 5500 µg*hr/mL (AML and ET)

Participants diagnosed with AML dosed: LY573636 targeting an AUCalb 7000 µg\*hr/mL as a 2-hour infusion on Day 1 of a 35-day cycle.

AUCalb 7000 µg*hr/mL (AML)

Participants diagnosed with AML dosed: LY573636 targeting an albumin-corrected exposure (AUCalb) 5500 micrograms\*hour per milliliter (µg\*hr/mL) as a 2-hour infusion on Day 1 of a 35-day cycle.

AUCalb 5500 µg*hr/mL (AML)

Participants diagnosed with essential thrombocythemia (ET) dosed: LY573636 targeting an AUCalb 5500 µg\*hr/mL as a 2-hour infusion on Day 1 of a 28-day cycle.

AUCalb 5500 µg*hr/mL (ET)

Total

Age, Continuous

Sex: Female, Male

Race

Race/Ethnicity, Customized

United States

Region of Enrollment

Participants who received at least 1 dose of study drug.

The primary outcome measure in this trial was not reached because the enrollment was stopped early before the maximum tolerated dose was reached.

Chief Medical Officer

No participants were analyzed since the MTD was not reached.

Recommended Phase 2 Dose of LY573636-Sodium in Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML) and Essential Thrombocythemia (ET)

LY573636 dose was based on an albumin-corrected exposure (AUCalb) to target a specific exposure range. Intravenous dosing is done on Day 1 of Cycle 1. Data are pooled together from all treatment groups.

LY573636

Participants who received the study drug and had pharmacokinetic (PK) data.

Pharmacokinetics Area Under the Curve(AUC) of LY573636 Above the Albumin-Corrected Threshold (AUCalb)

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

Spots Global Cancer Trial Database for Study of LY573636-sodium in Essential Thrombocythemia and Acute Myeloid Leukemia

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Study Description

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