Study Drug Administration:
If you are found to be eligible to take part in this study, you will receive decitabine by
vein over about 1 hour on Days 1-10 of each 28-day study cycle. Note that the start of future
cycles may be delayed if you have side effects to the study drug.
You will take venetoclax by mouth on Days 1-28 of the first cycle and Days 1-21 of all other
cycles. Each dose should be taken within 30 minutes after eating a meal (preferably
breakfast) with about a cup (8 ounces) of water. If the study doctor thinks it is needed
based on any side effects you may be having (such as low blood cell counts and/or
infections), your dose(s) of venetoclax may be delayed until it is thought to be safe for you
to receive it.
If venetoclax is not available at the start of treatment for any reason (insurance,
financial, transportation, and so on), you can begin receiving decitabine and venetoclax can
be added when it is available.
During Cycle 1, you will be admitted into the hospital as an inpatient for at least the first
3 days of combination therapy. During this time, you will also be given drugs to prevent
tumor lysis syndrome (TLS). TLS happens when breakdown products of the cancer cells entering
the blood stream, causing possible weakness, low blood pressure, muscle cramps, kidney
damage, and/or other organ damage. You may be given fluids (either by mouth or by vein) and
treatment with allopurinol or rasburicase. After Day 3, if there is If no evidence of TLS,
you may be discharged. You will then receive the rest of the study drug doses as an
If the study doctor thinks it is in your best interest, you may be able to also receive
standard of care therapies (such as sorafenib, midostaurin, imatinib, dasatinib, ponatinib,
and so on) while you are on study. The study doctor will discuss these treatments with you,
as well as their risks and benefits.
If the study doctor thinks it is needed for your safety, you may also receive cytarabine to
help prevent central nervous system side effects. Cytarabine will be given intrathecally
(through a spinal tap) on either Day 21 of Cycle 1 or Day 14 of Cycle 2.
Length of Study:
You may continue taking the study drugs for as long as the 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.
On Day 1 of each cycle (+/- 4 days), you will have a physical exam.
One (1) time every week during Cycles 1, 2 and 3, and then on Day 1 of each cycle after that
(+/- 4 days):
- Blood (about 1 tablespoon) will be drawn for routine tests.
- You will have a bone marrow biopsy and aspirate to check the status of the disease, and
for biomarker and cytogenetic testing (Day 21 [+/- 3 days]). If the study doctor thinks
it is needed, this will be repeated on Day 28. Additionally, you will have a bone marrow
biopsy and aspirate to check the status of the disease, for biomarker and for
cytogenetic testing at the end of Cycles 2 and 4, then every 1-3 cycles after that, then
at any time that the disease appears to get worse.
Additional Research Tests:
Blood (about 3 tablespoons) will be drawn for biomarker testing at the following time points
(within 24 hours). Biomarkers, which may include genetic biomarkers, are found in the blood
and tissue and may be related to your reaction to the study drug:
- Baseline (before the first decitabine dose), about Day 3 of Cycle 1, and between Days 21
to 28 of Cycle 1
- At the end of Cycles 2 and 4
- At any point that the disease appears to get worse
You will have a "cheek scrape" at the end of Cycle 1. These cells will be used to compare to
cancer cells to look for effects of the study drug. For this test, a small sample of cells
from the inside of your mouth will be collected by scraping a special brush against the
inside of your cheek a few times, until enough cells are collected.
Within 30 days after your last dose of study drug(s):
- You will have a physical exam.
- Blood (about 1 tablespoon) will be drawn for routine tests.
- You will have a bone marrow aspirate/biopsy to check the status of the disease and for
biomarker and cytogenetic testing.
If the disease responded to the study treatment, you will then be called every 3 to 6 months
for up to 5 years and asked about how you are doing. Each call should last about 15-30
1. Patients with AML, biphenotypic or bilineage leukemia (including a myeloid component)
or mixed phenotype acute leukemia (MPAL) who have failed prior therapy. Patients with
AML should have failed prior therapy or have relapsed after prior therapy. Patients
with isolated extramedullary AML are eligible.
2. Elderly (>60 year old) patients with newly diagnosed AML or mixed phenotype acute
leukemia (MPAL) not eligible for intensive chemotherapy.
3. AML patients with prior history of MDS or CMML who received any therapy or no therapy
for the MDS or CMML and progressed to AML, are eligible at the time of diagnosis of
AML regardless of any prior therapy for MDS. The WHO classification will be used for
4. Patients with high-risk MDS, and chronic myelomonocytic leukemia (CMML) with bone
marrow blasts between 10% and 20%, relapsed or refractory to prior hypomethylating
agent (HMA) therapy, defined as prior receipt of 4 cycles of HMA therapy with failure
to attain a response, or relapse after prior response to HMA therapy.
5. Age >/= 18 years
6. Eastern Cooperative Oncology Group (ECOG) Performance Status </=3
7. White blood cell count </= 10,000
8. Adequate renal function including creatinine < 2 unless related to the disease.
9. Adequate hepatic function including total bilirubin < 2x upper limit of normal (ULN)
unless increase is due to Gilbert's disease or leukemic involvement, and ALT < 3 x ULN
unless considered due to leukemic involvement
10. Provision of written informed consent
11. Oral hydroxyurea and/or one dose of cytarabine (up to 2 g/m2) for patients with
rapidly proliferative disease is allowed before the start of study therapy and while
the patient is on active study treatment through cycle 1, as needed, for clinical
benefit and after discussion with the PI. Concurrent therapy for central nervous
system (CNS) prophylaxis or continuation of therapy for controlled CNS disease is
12. 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
13. Women of childbearing potential must agree to use an adequate method of contraception
during the study and until 3 months after the last treatment. Males must be surgically
or biologically sterile or agree to use an adequate method of contraception during the
study until 3 months after the last treatment.
1. Patients having received any prior BCL2 inhibitor therapy.
2. Patients with t(15;17) karyotypic abnormality or acute promyelocytic leukemia
(French-American-British [FAB] class M3-AML).
3. Patients with symptomatic CNS leukemia or patients with poorly controlled CNS
4. Active and uncontrolled comorbidities including 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.
5. Patients with known infection with human immunodeficiency virus (HIV) or active
Hepatitis B or C.
6. Any other medical, psychological, or social condition that may interfere with study
participation or compliance, or compromise patient safety in the opinion of the
7. Pregnant or breastfeeding.