Single Agent Decitabine in TP53 Mutated Relapsed/Refractory Acute Myeloid Leukemia



Status:Recruiting
Conditions:Blood Cancer, Blood Cancer, Hematology
Therapuetic Areas:Hematology, Oncology
Healthy:No
Age Range:18 - Any
Updated:1/12/2019
Start Date:July 14, 2017
End Date:July 31, 2025
Contact:John Welch, M.D., Ph.D.
Email:jwelch@wustl.edu
Phone:(314) 362-2626

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An Open Label, Multicenter, Phase II Trial Testing Single Agent Decitabine in TP53 Mutated Relapsed/Refractory Acute Myeloid Leukemia

In this study, the investigators seek to determine whether decitabine therapy can improve
outcomes, specifically overall survival this selected subset of acute myeloid leukemia (AML)
patients with the poorest prognosis based on refractoriness to induction treatment and high
risk genetic mutations.


Inclusion Criteria:

- TP53 mutant AML. The presence of a TP53 mutation should be determined by Genoptix (or
institutional preferred equivalent assay). Detection of a TP53 mutation at the time of
initial diagnosis is sufficient for enrollment at the time of relapsed/refractory
disease. Detection of a TP53 mutation in either the peripheral blood or bone marrow is
adequate for enrollment. Alternatively, patients who have not had TP53 mutation
analysis performed, but who have > 20% TP53 positive cells by immunohistochemistry
detected on a bone marrow aspirate may also be enrolled,29 provided that mutation
analysis is requested at the time of enrollment.

- 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)
determined by Genoptix (or institutional preferred equivalent assay).

- 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.

- 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
immediately

- 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

Exclusion Criteria:

- Prior treatment with either decitabine or azacitidine or an investigational agent

- Acute promyelocytic leukemia with PML-RARA or t(15;17).

- History of 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
cardiac arrhythmia.

- 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 (other than AML) requiring active therapy or diagnosed within the last
year, with the exception of non-melanoma skin cancer which can be treated or in situ
malignancies (such as cervical, breast, prostate, etc.)

- Currently receiving any other investigational agents.

- Known central nervous system (CNS) leukemia or testicular involvement of 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.
We found this trial at
7
sites
101 Jessup Hall
Iowa City, Iowa 52242
(319) 335-3500
Principal Investigator: Carlos Vigil, M.D.
University of Iowa With just over 30,000 students, the University of Iowa is one of...
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Iowa City, IA
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185 Cambridge Street
Boston, Massachusetts 02114
617-724-5200
Principal Investigator: Timothy Graubert, M.D.
Phone: 617-643-0670
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Boston, MA
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5801 South Ellis Avenue
Chicago, Illinois 60637
 773.702.1234
Principal Investigator: Wendy Stock, M.D.
Phone: 773-834-8982
University of Chicago One of the world's premier academic and research institutions, the University of...
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Chicago, IL
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1100 Fairview Avenue North
Seattle, Washington 98109
(206) 667-5000
Principal Investigator: Elihu Estey, M.D.
Phone: 206-288-7176
Fred Hutchinson Cancer Research Center At Fred Hutchinson Cancer Research Center, our interdisciplinary teams of...
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Seattle, WA
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450 Brookline Ave
Boston, Massachusetts 2215
617-632-3000
Principal Investigator: Richard Stone, M.D.
Phone: 617-632-2214
Dana-Farber Cancer Institute Since it’s founding in 1947, Dana-Farber has been committed to providing adults...
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from
Boston, MA
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1515 Holcombe Blvd
Houston, Texas 77030
 713-792-2121
Principal Investigator: Hagop Kantarjian, M.D.
University of Texas M.D. Anderson Cancer Center The mission of The University of Texas MD...
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Houston, TX
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660 S Euclid Ave
Saint Louis, Missouri 63110
(314) 362-5000
Principal Investigator: John Welch, M.D., Ph.D.
Phone: 314-362-2626
Washington University School of Medicine Washington University Physicians is the clinical practice of the School...
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from
Saint Louis, MO
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