A Phase 1b, Open-label Study of LY2510924, Idarubicin and Cytarabine in Patients with Relapsed or Refractory Acute Myeloid Leukemia
The goal of this clinical research study is to learn about the safety of LY2510924 in combination with cytarabine and idarubicin in patients with relapsed or refractory AML. We will also study if LY2510924 in combination with cytarabine and idarubicin can help to control relapsed or refractory AML. LY2510924 is designed to help cancer cells move from the bone marrow into the bloodstream, where they are exposed to chemotherapy (in this case, cytarabine and idarubicin).
Disease Group: Leukemia
Treatment Agent: Cytarabine,Dexamethasone,Idarubicin,LY2510924
Treatment Location: Only at MDACC
Sponsor: Eli Lilly and Company,High Impact Clinical Research Support Program
Primary Objectives To determine the safety and toxicity profile of combination therapy with combination therapy of LY2510924, idarubicin and cytarabine in patients with relapsed or refractory AML. Secondary Objectives To assess the complete response (CR), CR with incomplete platelet recovery (CRp) and CR with incomplete blood count recovery (CRi) rates with combination therapy of LY2510924, idarubicin and cytarabine in patients with relapsed or refractory acute myeloid leukemia (AML). Determine the duration of response, disease-free survival, and overall survival. To assess the effect of LY2510924 on AML blasts when administered as monotherapy Exploratory objectives: To assess additional pharmacodynamic parameters relevant to CXCR4 inhibition
IRB Review and Approval Date: 05/09/2016
Recruitment Status: Open
Projected Accrual: N/A
1) All patients with histologically or cytologically confirmed relapsed
or refractory AML [except acute promyelocytic leukemia]; relapsed
disease or refractory (refractory to a non-high-dose
cytarabine-containing regimen only); receiving 1st, 2nd or 3rd salvage;
any cytogenetic or molecular abnormality. Patients with secondary AML
(after prior myelodysplasia or therapy for other cancers) will be included.
2) Patients with prior autologous and allogeneic hematopoietic stem cell transplantation are eligible if patients are off immunosuppression for greater than 14 days and have no evidence of active graft versus host disease (GVHD) except grade 1 skin GVHD.
3) Clinical laboratory values should be as follows: (a) White blood count < 30,000/µL; (b) Absolute Blasts in peripheral blood < 20,000 (treatment with Hydroxyurea is permitted up to 24 hrs prior to LY251092 administration to achieve blast counts < 20,000 prior to enrollment).
4) Patients must be 18-70 years old.
5) Patients must have a performance status of 0-2 (Zubrod scale).
6) Patients must have adequate renal function (serum creatinine less than or equal to 1.3 mg/dL). If creatinine is > 1 mg/dL the creatinine clearance should be > 40 mL/min as calculated using the Cockcroft-Gault formula.
7) Patients must have adequate hepatic function (bilirubin less than or equal to 2.0 mg/dl; serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) less than or equal to 3 X the upper limit of normal [ULN] for the reference lab unless due to leukemia or congenital hemolytic disorder or bilirubin excretion disorder). Patients with hepatic dysfunction (SGOT/SGPT up to less than or equal to 5 X ULN) due to organ infiltration by disease may be eligible after discussion with the Principal Investigator and appropriate dose adjustments will be considered.
8) Patients must have normal cardiac ejection fraction (left ventricular ejection fraction [LVEF] greater than or equal to 50%).
9) Patients must sign an informed consent form indicating that they are aware of the investigational nature of this study, in keeping with the policies of the hospital.
10) Negative urine or blood pregnancy test for women of childbearing potential.
11) Female patients must not be pregnant or lactating. Female patients of childbearing potential (including those <1 year post-menopausal) and male patients must agree to use contraception.
1) Patients with untreated or uncontrolled life-threatening infection.
2) Patients who have received chemotherapy and/or radiation therapy within 2 weeks unless there is evidence of rapidly progressive disease. In the event that subjects have received chemotherapy < 2 weeks from the date of enrollment, they may be included provided they have recovered from the associated non-hematological toxicities to less than or equal to grade 1. Hydroxyurea is allowed up to 24 hours prior to starting therapy in the setting of rapidly proliferating disease.
3) Patients who have received an investigational anti-cancer drug within two weeks (or five half-lives, whichever is shorter) of LY251092 administration.
4) History of myocardial infarction or cerebrovascular accident within 6 months of enrollment date.
5) History of another malignancy. Exception: Patients who have been disease-free for 3 years, or patients with a history of completely resected non-melanoma skin cancer and/or patients with indolent secondary malignancies, are eligible.
6) Any other medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient’s ability to sign informed consent or cooperate and participate in the study or with the interpretation of the results.
7) Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression (patients with controlled central nervous system (CNS) disease, i.e. asymptomatic and currently receiving concurrent intrathecal chemotherapy, are eligible upon discussion with the Principal InvestigatorI).
8) Known active Hepatitis B Virus (HBV), Human Immunodeficiency Virus (HIV) or Hepatitis C Virus (HCV) infection (patients with chronic or cleared HBV and HCV infection, are eligible).
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