Clinical Trials /

LY3214996 in Patients With AML Who Are Not Candidates for Standard Therapy

NCT04081259

Description:

This research study is evaluating a targeted therapy as a possible treatment for acute myeloid leukemia (AML) that has returned or not responded to standard treatment.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: LY3214996 in Patients With AML Who Are Not Candidates for Standard Therapy
  • Official Title: A Phase 1 Study of LY3214996, an ERK1/2 Inhibitor, in Patients With AML Who Are Not Candidates for Standard Therapy

Clinical Trial IDs

  • ORG STUDY ID: 19-263
  • NCT ID: NCT04081259

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
LY3214996LY3214996

Purpose

This research study is evaluating a targeted therapy as a possible treatment for acute myeloid leukemia (AML) that has returned or not responded to standard treatment.

Detailed Description

      This research study is a Phase I clinical trial, which tests the safety of an investigational
      drug and also tries to define the appropriate dose of the investigational drug to use for
      further studies. "Investigational" means that the drug is being studied.

      The U.S. Food and Drug Administration (FDA) has not approved LY3214996 as a treatment for any
      disease.

      LY3214996 is an extracellular signal-regulated kinase (ERK) inhibitor that is being developed
      as a treatment for patients with advanced cancer. ERK inhibitors stop the signal that a
      cancer cell receives telling it to grow. In this research study, the investigators are
      testing to see if LY3214996 is a safe treatment for AML that has returned or not responded to
      standard treatment. Several doses of the study drug will be explored in this study.
    

Trial Arms

NameTypeDescriptionInterventions
LY3214996Experimental-LY3214996 will be administered by mouth once daily continuously throughout each treatment cycle
  • LY3214996

Eligibility Criteria

        Inclusion Criteria:

          -  Participants must have histologically confirmed acute myeloid leukemia (AML) diagnosed
             per WHO criteria.

          -  Participants must have relapsed or refractory AML.

          -  Age ≥ 18 years.

          -  ECOG performance status ≤ 2

          -  Participants must have adequate organ function as defined below:

               -  Direct Bilirubin ≤ 1.5 × institutional upper limit of normal (ULN)

               -  AST (SGOT) and ALT(SGPT) ≤ 2.5 × institutional ULN, OR

               -  AST (SGOT) and ALT (SGPT) ≤ 5 × institutional ULN if elevation is a result of
                  leukemia

               -  Creatinine Clearance ≥ 60 mL/min/1.73 m2 (calculated via the Cockcroft-Gault
                  equation)

          -  The effects of LY3214996 on the developing human fetus are unknown. For this reason
             and because anti-cancer agents are known to be teratogenic, women of child-bearing
             potential and men must agree to use adequate contraception (hormonal or barrier method
             of birth control; abstinence) prior to study entry and for the duration of study
             participation. Should a woman become pregnant or suspect she is pregnant while she or
             her partner is participating in this study, she should inform her treating physician
             immediately. Men and women treated or enrolled on this protocol must agree to use
             adequate contraception prior to the study, for the duration of study participation,
             and 4 months after completion of LY3214996 administration.

          -  Ability to understand and the willingness to sign a written informed consent document.

          -  Ability to swallow and retain oral medication.

          -  Participants must have resolution of adverse events related to prior anti-cancer
             therapies to ≤ CTCAE Grade 2 or baseline

        Exclusion Criteria:

          -  Participants who have had chemotherapy, other investigational therapy, immunotherapy,
             or radiotherapy within 2 weeks prior to the first dose of study medication. ATRA
             treatment is permitted with no required washout if treatment duration was for less
             than 1 week. Hydroxyurea is allowed with no required washout. For participants with an
             absolute peripheral blast count > 20 K/µL, hydroxyurea may be administered up to day
             14 of protocol therapy with a maximum allowed dose of 6 g per day.

          -  Participants who have received oral tyrosine kinase inhibitors (TKIs) within 5
             half-lives of the first dose of study medication.

          -  Participants who have had major surgery within 4 weeks prior to the first dose of
             study medication.

          -  Participants who have had a prior stem cell transplant (SCT) within 90 days prior to
             the first dose of study medication. Additionally, participants having undergone prior
             SCT must be off calcineurin inhibitor therapy for at least 28 days prior to the first
             dose of study medication.

          -  Participants with active > Grade 1 acute or chronic Graft v. Host Disease (GvHD) who
             are receiving immunosuppressive therapy other than prednisone. Use of prednisone is
             permitted only if participants have been maintained at a steady dose of < 20 mg/day
             for at least 5 days prior to the first dose of study medication.

          -  Participants with known active CNS leukemia involvement. Participants with no known
             history of CNS leukemia are not required to undergo lumbar puncture (LP) for trial
             eligibility unless the participant is symptomatic as judged by the treating
             investigator. Participants with a history of CNS leukemia involvement are eligible
             provided that the CNS disease has been adequately treated and cleared prior to study
             enrollment as judged by the treating investigator.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to LY3214996.

          -  Uncontrolled intercurrent illness including, but not limited to: ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Pregnant women are excluded from this study because LY3214996 is an agent with the
             potential for teratogenic or abortifacient effects. Because there is an unknown but
             potential risk for adverse events in nursing infants secondary to treatment of the
             mother with LY3214996, breastfeeding should be discontinued if the mother is treated
             with LY3214996. A negative serum pregnancy test is required for women of childbearing
             potential prior to study entry.

          -  Participants who are known to be seropositive for human immunodeficiency virus (HIV)
             or hepatitis B or C. Testing is not required for eligibility.

          -  Participants with a history or findings of central or branch retinal artery or venous
             occlusion with significant vision less, or other retinal diseases causing visual
             impairment as determined by an ophthalmologist.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Limiting Toxicity
Time Frame:21 days
Safety Issue:
Description:Toxicities occurring following administration of protocol therapy, measured using CTCAE 5.0 criteria.

Secondary Outcome Measures

Measure:Overall Response Rate
Time Frame:6 months
Safety Issue:
Description:Rate of complete remission (CR), CR with incomplete count recovery (CRi), and partial remission (PR) using IWG and ELN criteria.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Acute Myeloid Leukemia
  • AML
  • ERK
  • Relapsed
  • Refractory
  • LY3214996

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