Overview

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

Status:
Recruiting
Trial end date:
2023-04-30
Target enrollment:
0
Participant gender:
All
Summary
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.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Dana-Farber Cancer Institute
Collaborator:
Eli Lilly and Company
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

- Considerations of concurrent use of CYP3A4 inhibitors

Dose escalation phase:

- ARM A: Participants must not be receiving any concurrent antifungal agents that are
moderate/strong CYP3A4 inhibitors. These include but are not limited to:
isavuconazole, itraconazole, fluconazole, ketoconazole, posaconazole, and
voriconazole.

- ARM B: Participants must be receiving concurrent antifungal agents that are
moderate/strong CYP3A4 inhibitors. These include but are not limited to:
isavuconazole, itraconazole, fluconazole, ketoconazole, posaconazole, and
voriconazole.

Expansion Phase:

Participants not receiving concurrent antifungal agents that are moderate/strong CYP3A4
inhibitors are eligible to enroll at MTD determined upon completion of dose-escalation
cohort Arm A. Participants receiving concurrent antifungal agents that are moderate/strong
CYP3A4 inhibitors are eligible to enroll at MTD determined upon completion of
dose-escalation cohort Arm B.

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.