The goal of this clinical research study is to find the highest tolerated dose of the
combination of lirilumab and 5-azacytidine that can be given to patients with AML or
high-risk MDS. Researchers also want to learn if the drug combination can help to control the
disease. The safety of the drug combination will also be studied.
This is an investigational study. Lirilumab is not FDA approved or commercially available.
5-azacytidine is FDA-approved and commercially available for the treatment of MDS, which can
lead to AML, but it has not been approved for the treatment of AML. The use of these drugs in
combination is investigational. The study doctor can explain how the drugs are designed to
Up to 64 participants will be enrolled in this study. All will take part at MD Anderson.
If you are found to be eligible to take part in this study, you will be assigned to a study
group based on when you join this study. Up to 5 groups of up to 6 participants will be
enrolled in the lead-in phase of the study, and up to 40 participants will be enrolled in
If you are enrolled in the lead-in phase, the dose of lirilumab and 5-azacytidine you receive
will depend on when you joined this study. The first group of participants will receive the
starting dose combination level. If intolerable side effects are seen, the next group may
receive a lower dose level of lirilumab and/or 5-azacytidine. This will continue until the
highest tolerable combination dose is found.
If you are enrolled in Phase 2, you will receive lirilumab and 5-azacytidine at the highest
dose that was tolerated in the lead-in phase.
You will receive the study drugs in cycles that are about 28 days long. However, these cycles
may be shorter or longer depending on if/how the disease responds to the treatment, how your
bone marrow reacts to treatment, and what the study doctor thinks is in your best interest.
On Days 1-7 of each study cycle, you will receive 5-azacytidine daily either by vein over
about 1 hour or by an injection under the skin. It is possible that you will start receiving
the drug one way and switch to the other if the study doctor thinks it is in your best
On Day 8 (+/- 2 days) of each cycle, you will also receive lirilumab by vein over about 1
Your dose of 5-azacytidine may be raised, lowered, and/or delayed if the doctor thinks it is
in your best interest. Your dose of lirilumab may also be delayed if the doctor thinks it is
in your best interest.
Though you will receive lirilumab at MD Anderson every time you receive it, it is possible
that after the first 4 cycles you will be able to receive 5-azacytidine at a more convenient
location to you. Talk to the study staff about receiving the drug at a local treatment
On Day 1 of each cycle, you will have a physical exam.
During the first 3 cycles, blood (about 1 tablespoon) will be drawn for routine tests 1 time
each week. After the first 3 cycles, blood (about 1 tablespoon) will be drawn for routine
tests every 2-4 weeks.
On Day 28 of Cycle 1 (+/- 7 days), then every 1-3 cycles after that, you will have a bone
marrow aspiration and/or biopsy to check the status of the disease.
You will have blood draws and/or bone marrow aspirations at any time that the doctor thinks
it is needed while you are on study.
After Cycle 1, you may be able to have study tests performed at a local clinic. Talk to the
study staff about this option.
Length of Study:
It is planned that you may receive up to 24 cycles of the study drug, but it is possible that
you may continue taking the study drug after this if the study doctor thinks it is in your
best interest. You will no longer be able to take the study drug if the disease gets worse,
if intolerable side effects occur, or if you are unable to follow study directions.
Your participation on the study will be over after the follow-up visits.
If you are taken off or if you leave the study before the end of Cycle 24, the following
tests and procedures will be performed:
- You will have a physical exam.
- Blood (about 2-3 tablespoons) will be drawn for routine tests.
- If the doctor thinks it is needed, you will have a bone marrow aspirate to check the
status of the disease.
You will be asked to return to the clinic for a follow-up visit with a physical exam about 30
days after you stop receiving the study drugs. If you cannot come to the clinic, you will be
called about 30 days after you go off study and asked if you have had any side effects and/or
any new treatment(s). This call will last about 5 minutes.
If you go off study for reasons other than the disease getting worse, you will be called
every 3-6 months for up to 5 years and asked about how you are doing. Each call should last
about 5 minutes.
1. Patients with AML or biphenotypic or bilineage leukemia who have failed at least one
prior therapy. Patients with AML should have failed prior therapy or have relapsed
after prior therapy.
2. Patients should not be eligible or able to receive approved therapy of confirmed
clinical benefit in this patient population.
3. Patients with MDS or CMML who received therapy for the MDS or CMML and progress to AML
are eligible at the time of diagnosis of AML regardless any prior therapy for AML. The
WHO classification will be used for AML.
4. Prior therapy with hydroxyurea, chemotherapy, biological or targeted therapy (e.g.
FLT3 inhibitors, other kinase inhibitors), or hematopoietic growth factors is allowed
5. Age >/=18 years
6. Eastern Cooperative Oncology Group (ECOG) Performance Status </= 2
7. Adequate organ function: total bilirubin </= 2 times upper limit of normal (x ULN)
(</= 3 x ULN if considered to be due to leukemic involvement or Gilbert's syndrome);
aspartate aminotransferase or alanine aminotransferase </= 2.5 x ULN (</= 5.0 x ULN if
considered to be due to leukemic involvement); serum creatinine </= 2 x ULN or
8. Patients must provide written informed consent
9. 9) In the absence of rapidly progressing disease, the interval from prior treatment to
time of initiation of 5-azacytidine and lirilumab will be at least 2 weeks OR at least
5 half-lives for cytotoxic/noncytotoxic agents. Use of one dose of cytarabine (up to 2
g/m2) is allowed prior to the start of study therapy or hydroxyurea for patients with
rapidly proliferative disease is allowed before the start of study therapy and while
the patient is on active study treatment, as needed, for clinical benefit and after
discussion with the PI. Concurrent therapy for CNS prophylaxis or continuation of
therapy for controlled CNS disease is permitted
10. Females must be surgically or biologically sterile or postmenopausal (amenorrheic for
at least 12 months) or if of childbearing potential, must have a negative serum or
urine pregnancy test within 72 hours before the start of the treatment
11. Women of childbearing potential must agree to use an adequate method of contraception
during the study and until 30 days after the last treatment. Males must be surgically
or biologically sterile or agree to use an adequate method of contraception during the
study until 30 days after the last treatment. The details of adequate method of
contraception are shown in the protocol section 4.1.10 Women are considered
post-menopausal and not of child bearing potential if they have had 12 months of
natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age
appropriate, history of vasomotor symptoms) or have had surgical bilateral
oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago.
In the case of oophorectomy alone, only when the reproductive status of the woman has
been confirmed by follow up hormone level assessment is she considered not of child
1. Patients with known allergy or hypersensitivity to lirilumab, 5-azacytidine, or any of
their components. Patients who have previously been treated with lirilumab in
combination with 5-azacytidine will be excluded.
2. Patients with a known history of severe interstitial lung disease or severe
pneumonitis or active pneumonitis that is uncontrolled in the opinion of the treating
3. Patients with a known history of any of the following autoimmune diseases are
excluded: (a) patients with a history of inflammatory bowel disease (including Crohn's
disease and ulcerative colitis) (b) patients with a history of rheumatoid arthritis,
systemic progressive sclerosis [scleroderma], Systemic Lupus Erythematosus, autoimmune
vasculitis [e.g., Wegener's Granulomatosis]).
4. Patients with organ allografts (such as renal transplant) are excluded
5. Patients with allogeneic stem cell transplantation within the last 6 months or
patients with active GVHD will be excluded.
6. Ongoing immunosuppressive therapy, including cyclosporine and tacrolimus. Patients who
are on high dose steroid. Note: Subjects may be using systemic corticosteroids (daily
doses </= 10 mg of prednisone or equivalent) or topical or inhaled corticosteroids.
7. Patients with symptomatic CNS leukemia or patients with poorly controlled CNS
8. Active and uncontrolled disease/(active uncontrolled infection, uncontrolled
hypertension despite adequate medical therapy, active and uncontrolled congestive
heart failure NYHA class III/IV, clinically significant and uncontrolled arrhythmia)
as judged by the treating physician.
9. Patients with active and uncontrolled Human Immunodeficiency Virus (HIV) infection
will be excluded. However, patients with well controlled HIV infection will be
10. Patients known to be positive for hepatitis B by surface antigen expression. Known to
have active hepatitis C infection (positive by polymerase chain reaction or on
antiviral therapy for hepatitis C within the last 6 months)
11. Any other medical, psychological, or social condition that may interfere with study
participation or compliance, or compromise patient safety in the opinion of the
12. Patients unwilling or unable to comply with the protocol.
13. Pregnant or breastfeeding
14. Acute promyelocytic leukemia (APL).