- TP53 mutant relapsed/refractory AML following 7+3 (or similar cytarabine containing
induction chemotherapy for AML) disease detected by one of the following methods:
- bone marrow blasts > 5%, or
- Hematologics flow cytometry assay (threshold > 0.5%) (alternative equivalent
assay may be substituted), or
- Persistent cytogenetic abnormality (e.g. del5, del17p, etc), by FISH or
conventional karotyping, or
- Persistent TP53 mutation (at least 5 variant reads with at least 50x coverage).
- Patients with > 10% blasts on a day +14 bone marrow biopsy following 7+3 may either be
enrolled or may be treated with a course of standard re-induction (e.g. 5+2 or
similar) and then re-evaluated for response. Eligible patients will meet any of the
above criteria on a subsequent biopsy.
The presence of a TP53 mutation should be determined by Genoptix (or institutional
preferred equivalent assay) for all patients. Detection of a TP53 mutation at the time of
initial diagnosis is sufficient for enrollment. Detection of a TP53 mutation in either the
peripheral blood or bone marrow is adequate for enrollment.
- Bone marrow and organ function as defined below:
- Peripheral white blood cell count < 50,000/mcl (patients may receive hydroxyurea
as necessary for cytoreduction),
- Total bilirubin < 1.5 x upper limit of normal,
- AST and ALT < 2.5 x upper limit of normal,
- Serum creatinine < 2.0 x upper limit of normal, and,
- At least 18 years of age.
- Women of childbearing 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 participating in this study, she must inform her treating physician
- Ability to understand and willingness to sign an IRB approved written informed consent
document (or that of legally authorized representative, if applicable
- Performance status ≤ 3
- Prior treatment with either decitabine or azacitidine.
- Acute promyelocytic leukemia with PML-RARA or t(15;17).
- Active HIV, Hepatitis B, or Hepatitis C infection.
- Concurrent illness including, but not limited to, ongoing uncontrolled infection,
symptomatic NYHA class 3 or 4 congestive heart failure, unstable angina pectoris, or
- Radiation therapy within 14 days of enrollment.
- Chemotherapy administration in the 14 days preceding enrollment with the exception of
hydroxyurea, which can be continued until Cycle 2. A washout period for oral tyrosine
kinase inhibitors (e.g. Jakafi, etc) is not required, although tyrosine kinase
inhibitors therapy must be discontinued prior to enrollment.
- Malignancies requiring active therapy, with the exception of basal cell or squamous
cell carcinoma of the skin which can be treated with local resection only or carcinoma
in situ of the cervix.
- Currently receiving any other investigational agents.
- Known central nervous system (CNS) leukemia.
- A history of allergic reactions attributed to compounds of similar chemical or
biologic composition to decitabine or other agents used in the study.
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative
urine pregnancy test within 7 days of study entry.