LY2510924, Idarubicin and Cytarabine in Patients With Relapsed or Refractory Acute Myeloid Leukemia

• ClinicalTrials.gov Identifier: NCT02652871
• Recruitment Status: Completed
• First Posted: January 12, 2016
• Last Update Posted: November 15, 2019
• Sponsor: M.D. Anderson Cancer Center
• Collaborators: Eli Lilly and Company; High Impact Clinical Research Support Program
• Information provided by (Responsible Party): M.D. Anderson Cancer Center

Study Description

Brief Summary:

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).

This is an investigational study. LY2510924 is not FDA approved or commercially available. Its use in this study is investigational. Cytarabine and idarubicin are approved to treat certain types of leukemia. Their use in this study in combination with LY2510924 is investigational.

Up to 36 patients will take part in this study. All will be enrolled at MD Anderson.

Condition or disease	Intervention/treatment	Phase
Leukemia	Drug: LY2510924; Drug: Idarubicin; Drug: Cytarabine	Phase 1

  Show Detailed Description

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 36 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1b, Open-label Study of LY2510924, Idarubicin and Cytarabine in Patients With Relapsed or Refractory Acute Myeloid Leukemia
• Actual Study Start Date: May 9, 2016
• Actual Primary Completion Date: July 16, 2019
• Actual Study Completion Date: July 16, 2019

Arms and Interventions

Arm

Intervention/treatment

Experimental: LY2510924 + Idarubicin + Cytarabine; Dose Escalation Phase: Starting dose level of LY2510924 is 10 mg subcutaneously each day of a 28 day cycle. Dose escalated in successive cohorts of patients. On Day 8, LY2510924 administered after bone marrow aspiration and/or biopsy is performed. Dose Expansion Phase: LY2510924 given at the maximum tolerated dose (MTD) from Dose Escalation Phase. Dose Escalation Phase: Idarubicin 12 mg/m2 by vein given on Days 8 and 9 of a 28 day cycle. In patients > 60 years of age Idarubicin given for 2 days. Dose Expansion Phase: Idarubicin 8 mg/m2 by vein for 2 days. Dose Escalation Phase: Cytarabine 1.5 gm/m2 by vein daily for 4 days (age < 60 years). In patients > 60 years of age Cytarabine given for 3 days only. Dose Expansion Phase: Cytarabine 0.75 gm/m2 by vein for 3 days.

Drug: LY2510924; Dose Escalation Phase: Starting dose level of LY2510924 is 10 mg subcutaneously each day of a 28 day cycle. Dose escalated in successive cohorts of patients. Dose Expansion Phase: LY2510924 given at the maximum tolerated dose (MTD) from Dose Escalation Phase.; Drug: Idarubicin; Dose Escalation Phase: Idarubicin 12 mg/m2 by vein given on Days 8 and 9 of a 28 day cycle. In patients > 60 years of age Idarubicin given for 2 days. Dose Expansion Phase: Idarubicin 8 mg/m2 by vein for 2 days.; Other Name: Idamycin; Drug: Cytarabine; Dose Escalation Phase: Cytarabine 1.5 gm/m2 by vein daily for 4 days (age < 60 years). In patients > 60 years of age Cytarabine given for 3 days only. Dose Expansion Phase: Cytarabine 0.75 gm/m2 by vein for 3 days.; Other Names: Ara-C; Cytosar; DepoCyt; Cytosine Arabinosine Hydrochloride

Outcome Measures

Primary Outcome Measures :

1. Dose Limiting Toxicity of LY2510924, Idarubicin and Cytarabine in Patients with Relapsed or Refractory Acute Myeloid Leukemia [ Time Frame: 30 days post transplant ]
   Dose-limiting toxicity (DLT) defined as a clinically significant adverse event or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness or concomitant medications. To be considered a DLT such toxicity must be possibly, probably or definitely related to LY2510924. Toxicity evaluated using the National Cancer Institute (NCI) Version 4.0 criteria.

Secondary Outcome Measures :

1. Response of LY2510924, Idarubicin and Cytarabine in Patients with Relapsed or Refractory Acute Myeloid Leukemia [ Time Frame: 56 days ]

   International Working Group Criteria used to define response.

   Complete remission (CR): Participant must be free of all symptoms related to leukemia and have an absolute neutrophil count (ANC), 1.0 x 109/L, platelet count, 100 x 109/L, and normal bone marrow differential (5% blasts).

   Complete remission without platelet recovery (CRp): As per CR but platelet count 100 x 109/L.

   Complete Remission with Incomplete Blood Count Recovery (CRi): Peripheral blood and bone marrow results as for CR except for ANC < 1.0 x 109/L with or without platelet count < 100 x 109/L.

   Partial remission (PR): CR with 6 to 25% abnormal cells in the marrow or 50% decrease in bone marrow blasts.

   Morphologic leukemia-free state: Normal marrow differential (5% blasts); neutrophil and platelet counts are not considered.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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).

Contacts and Locations

Locations

United States, Texas

University of Texas MD Anderson Cancer Center

Houston, Texas, United States, 77030

Sponsors and Collaborators

M.D. Anderson Cancer Center

Eli Lilly and Company

High Impact Clinical Research Support Program

Investigators

• Principal Investigator: Marina Konopleva, MD, PHD; M.D. Anderson Cancer Center

More Information

Additional Information:

University of Texas MD Anderson Cancer Center Website 

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT02652871 History of Changes
• Other Study ID Numbers: 2015-0436; NCI-2016-00259 ( Registry Identifier: NCI CTRP )
• First Posted: January 12, 2016
• Last Update Posted: November 15, 2019
• Last Verified: November 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:

Leukemia; Acute Myeloid Leukemia; AML; Relapsed or Refractory; Acute myelogenous leukemia; LY2510924; Idarubicin; Idamycin; Cytarabine; Ara-C; Cytosar; DepoCyt; Cytosine Arabinosine Hydrochloride

Additional relevant MeSH terms:

Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Neoplasms by Histologic Type; Neoplasms; Cytarabine; Idarubicin; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antiviral Agents; Anti-Infective Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antibiotics, Antineoplastic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors