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

• Sponsor: Washington University School of Medicine (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03063203
• Collaborator: Janssen Pharmaceuticals (Industry), National Institutes of Health (NIH) (NIH), National Cancer Institute (NCI) (NIH)
• Enrollment: 17
• Location: 1
• Arm: 1
• Actual Duration (Months): 56
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia; Acute Myeloid Leukemia, Relapsed, Adult	Drug: Decitabine; Procedure: Bone marrow biopsy/aspirate; Procedure: Peripheral blood draw; Procedure: Skin biopsy; Procedure: Buccal swab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 17 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label, Multicenter, Phase II Trial Testing Single Agent Decitabine in TP53 Mutated Relapsed/Refractory Acute Myeloid Leukemia
• Actual Study Start Date: Jul 14, 2017
• Actual Primary Completion Date: Feb 13, 2021
• Actual Study Completion Date: Mar 16, 2022

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Decitabine Cycle 1: All patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle Cycle 2: Patients with bone marrow blast counts < 5% may receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of a 28-day cycle. All other patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle. Cycle 3 and subsequent cycles: All patients will receive 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of the 28-day cycle

Drug: Decitabine; After 2 cycles, patients with progressive disease or relapse (a clear progression with at least >20% bone marrow blasts and an increase of at least 50% from prior biopsy) should be removed from protocol and proceed to salvage treatment according to center preference Transplant eligible patients who achieve CR, CRc, or CRi, after 3 cycles with a suitable donor will proceed to conditioning regimen and transplant Transplant eligible patients with PR after 3 cycles may be removed from protocol and proceed to salvage treatment according to center preference Transplant eligible patients with a suitable donor who achieve mLFS, CR, CRc, or CRi, may proceed to transplant after at 3 cycles Transplant ineligible patients with (CR, CRc or CRi, PR) will continue on maintenance doses Transplant ineligible patient with SD after cycle 4 may be removed from protocol and proceed to alternative treatment or continue on protocol according to treating physician's preference.; Other Names: 5-aza-2'-deoxycytidine ; Procedure: Bone marrow biopsy/aspirate; Baseline, Cycle 1 Day 10, Cycle 1 Day 28, Cycle 2 Day 28, Cycle 3 Day 28, and Progression or relapse Biopsy/aspirate on Cycle 1 Day 10 is for participants enrolled at Washington University only Biopsy/aspirate on Cycle 2 Day 28 is at the discretion of the treating physician; Procedure: Peripheral blood draw; -Baseline, Cycle 1 Day 10, Cycle 1 Day 28, Cycle 2 Day 28, Cycle 3 Day 28, and Progression/Relapse; Procedure: Skin biopsy; Optional but if refuse skin biopsy then participant can provided buccal swab There is no required time frame for this sample - it may have been collected months or even years prior to the first dose of decitabine If WBC at time of enrollment is >30,000/µl, skin biopsy should be collected at the time of C1D28 bone marrow biopsy or thereafter; Procedure: Buccal swab; -Baseline (if skin biopsy declined) and Cycle 2 Day 28

Outcome Measures

Primary Outcome Measures

1. Overall Survival of Participants With TP53 Mutation [1 year]

   Overall survival (OS) is defined as the time from enrollment to death due to any cause. For a patient who is not known to be alive at the end of study follow up, observation of OS is censored on the date the patient was last known to be alive To be evaluable for this outcome measure the participant would have to have received at least one dose of decitabine

Secondary Outcome Measures

1. Percentage of Responding TP53 Mutated Patients (CR, CRi) [12 weeks]

   Complete remission (CR) - Defined as bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count >1.0 x 109/L (1,000/μL); platelet count >100 x 109/L (100,000/μL). Complete remission with incomplete hematologic recovery (CRi): All CR criteria except for residual neutropenia - <1.0 x 109/L (1,000/μL) or thrombocytopenia -<100 x 109/L (100,000/μL)

2. Time to Stem Cell Transplant Among Participants Who Are Suitable Candidates for Transplant and Have an Identified Donor [12 weeks]

   Document the number of days that it takes each participant to reach transplant Transplant eligible participants are those who achieve complete remission (CR), cytogenetic complete remission (CRc), complete remission with incomplete hematologic recovery (CRi), or morphologic leukemia free state (mLFS) per 2017 ELN AML Recommendations.

3. Median Time to Leukemia Relapse (TTLR) in Non-transplant Patients [2 years]

   -Recurrence/morphologic relapse - Defined as relapse following complete remission is defined as reappearance of blasts in the blood or the finding of ≥ 5% blasts in the bone marrow, not attributable to any other cause. New dysplastic changes is considered relapse. If there are no blasts in the peripheral blood and 5-20% blasts in the bone marrow, bone marrow biopsy should be repeated in > 1 week to confirm relapse.

4. Event-free Survival (EFS) [2 year]

   -Event-free survival is defined as the interval from the date of first dose of study drug to date of treatment failure, recurrence, death due to any cause, or loss to follow up.

5. Average Number of Hospital Days [During cycles 1 and 2 (60 days)]

   -Document number of hospital days that each participant stays and obtain average for all evaluable participants

6. Response Compared Between Patients With Morphologically Evident Disease Versus Patients With Molecularly Detected Disease at the Time of Enrollment [Through 12 weeks]

   Morphologically evident disease (>5% blasts by cytomorphology) Molecularly detected disease (disease detected with flow cytometry, cytogenetic, or mutational analysis if ≤ 5% blasts by cytomorphology) Response will be assessed according to the 2017 European LeukemiaNet (ELN) Acute Myeloid Leukemia (AML) recommendations

7. Survival Compared Between Patients With Morphologically Evident Disease Versus Patients With Molecularly Detected Disease at the Time of Enrollment [2 years]

   Morphologically evident disease (>5% blasts by cytomorphology) Molecularly detected disease (disease detected with flow cytometry, cytogenetic, or mutational analysis with ≤ 5% blasts by cytomorphology)

8. Response Compared Between Patients With de Novo AML Versus Patients With Secondary AML Versus Patients With Treatment-related AML [Through 12 weeks]

   -Response will be assessed according to the 2017 European LeukemiaNet (ELN) Acute Myeloid Leukemia (AML) recommendations

9. Survival Compared Between Patients With de Novo AML Versus Patients With Secondary AML Versus Patients With Treatment-related AML [2 years]

10. Response Compared Between Patients With Presence of Cytogenetic Abnormalities in Addition to TP53 Mutations Versus Patients With Absence of Cytogenetic Abnormalities in Addition to TP53 Mutations [12 weeks]

    -Response will be assessed according to the 2017 European LeukemiaNet (ELN) Acute Myeloid Leukemia (AML) recommendations

11. Survival Compared Between Patients With Presence of Cytogenetic Abnormalities in Addition to TP53 Mutations Versus Patients With Absence of Cytogenetic Abnormalities in Addition to TP53 Mutations [2 years]

12. Median Number of Hospital Stays [During cycles 1 and 2 (60 days)]

    -Document number of hospital days that each participant stays and obtain median for all evaluable participants

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 7 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Washington University School of Medicine	Saint Louis	Missouri	United States	63110

Sponsors and Collaborators

• Washington University School of Medicine
• Janssen Pharmaceuticals
• National Institutes of Health (NIH)
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: John Welch, M.D., Ph.D., Washington University School of Medicine

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 1, 2020
• Informed Consent Form - Dec 2, 2020

More Information

Additional Information:

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Publications

None provided.

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT03063203
• Other Study ID Numbers: 201911185-1001; 3P50CA171963-06S1
• First Posted: Feb 24, 2017
• Last Update Posted: Jun 2, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Decitabine

Study Results

Participant Flow

Arm/Group Title	Decitabine
Arm/Group Description	Cycle 1: All patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle Cycle 2: Patients with bone marrow blast counts < 5% may receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of a 28-day cycle. All other patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle. Cycle 3 and subsequent cycles: All patients will receive 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of the 28-day cycle
Period Title: Overall Study
STARTED	17
COMPLETED	3
NOT COMPLETED	14

Baseline Characteristics

Arm/Group Title	Decitabine
Arm/Group Description	Cycle 1: All patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle Cycle 2: Patients with bone marrow blast counts < 5% may receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of a 28-day cycle. All other patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle. Cycle 3 and subsequent cycles: All patients will receive 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of the 28-day cycle
Overall Participants	17
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	61
Sex: Female, Male (Count of Participants)
Female	6 35.3%
Male	11 64.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	17 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 5.9%
White	16 94.1%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	17 100%

Outcome Measures

1. Primary Outcome

Title	Overall Survival of Participants With TP53 Mutation
Description	Overall survival (OS) is defined as the time from enrollment to death due to any cause. For a patient who is not known to be alive at the end of study follow up, observation of OS is censored on the date the patient was last known to be alive To be evaluable for this outcome measure the participant would have to have received at least one dose of decitabine
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Decitabine
Arm/Group Description	Cycle 1: All patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle Cycle 2: Patients with bone marrow blast counts < 5% may receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of a 28-day cycle. All other patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle. Cycle 3 and subsequent cycles: All patients will receive 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of the 28-day cycle
Measure Participants	17
Median (95% Confidence Interval) [days]	244

2. Secondary Outcome

Title	Percentage of Responding TP53 Mutated Patients (CR, CRi)
Description	Complete remission (CR) - Defined as bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count >1.0 x 109/L (1,000/μL); platelet count >100 x 109/L (100,000/μL). Complete remission with incomplete hematologic recovery (CRi): All CR criteria except for residual neutropenia - <1.0 x 109/L (1,000/μL) or thrombocytopenia -<100 x 109/L (100,000/μL)
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Decitabine
Arm/Group Description	Cycle 1: All patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle Cycle 2: Patients with bone marrow blast counts < 5% may receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of a 28-day cycle. All other patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle. Cycle 3 and subsequent cycles: All patients will receive 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of the 28-day cycle
Measure Participants	17
Count of Participants [Participants]	5 29.4%

3. Secondary Outcome

Title	Time to Stem Cell Transplant Among Participants Who Are Suitable Candidates for Transplant and Have an Identified Donor
Description	Document the number of days that it takes each participant to reach transplant Transplant eligible participants are those who achieve complete remission (CR), cytogenetic complete remission (CRc), complete remission with incomplete hematologic recovery (CRi), or morphologic leukemia free state (mLFS) per 2017 ELN AML Recommendations.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Decitabine
Arm/Group Description	Cycle 1: All patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle Cycle 2: Patients with bone marrow blast counts < 5% may receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of a 28-day cycle. All other patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle. Cycle 3 and subsequent cycles: All patients will receive 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of the 28-day cycle
Measure Participants	7
Median (Full Range) [days]	117

4. Secondary Outcome

Title	Median Time to Leukemia Relapse (TTLR) in Non-transplant Patients
Description	-Recurrence/morphologic relapse - Defined as relapse following complete remission is defined as reappearance of blasts in the blood or the finding of ≥ 5% blasts in the bone marrow, not attributable to any other cause. New dysplastic changes is considered relapse. If there are no blasts in the peripheral blood and 5-20% blasts in the bone marrow, bone marrow biopsy should be repeated in > 1 week to confirm relapse.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Decitabine
Arm/Group Description	Cycle 1: All patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle Cycle 2: Patients with bone marrow blast counts < 5% may receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of a 28-day cycle. All other patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle. Cycle 3 and subsequent cycles: All patients will receive 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of the 28-day cycle
Measure Participants	4
Median (Full Range) [days]	308

5. Secondary Outcome

Title	Event-free Survival (EFS)
Description	-Event-free survival is defined as the interval from the date of first dose of study drug to date of treatment failure, recurrence, death due to any cause, or loss to follow up.
Time Frame	2 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Decitabine
Arm/Group Description	Cycle 1: All patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle Cycle 2: Patients with bone marrow blast counts < 5% may receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of a 28-day cycle. All other patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle. Cycle 3 and subsequent cycles: All patients will receive 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of the 28-day cycle
Measure Participants	17
Median (95% Confidence Interval) [days]	227

6. Secondary Outcome

Title	Average Number of Hospital Days
Description	-Document number of hospital days that each participant stays and obtain average for all evaluable participants
Time Frame	During cycles 1 and 2 (60 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Decitabine
Arm/Group Description	Cycle 1: All patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle Cycle 2: Patients with bone marrow blast counts < 5% may receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of a 28-day cycle. All other patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle. Cycle 3 and subsequent cycles: All patients will receive 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of the 28-day cycle
Measure Participants	17
Mean (Full Range) [days]	10.3

7. Secondary Outcome

Title	Response Compared Between Patients With Morphologically Evident Disease Versus Patients With Molecularly Detected Disease at the Time of Enrollment
Description	Morphologically evident disease (>5% blasts by cytomorphology) Molecularly detected disease (disease detected with flow cytometry, cytogenetic, or mutational analysis if ≤ 5% blasts by cytomorphology) Response will be assessed according to the 2017 European LeukemiaNet (ELN) Acute Myeloid Leukemia (AML) recommendations
Time Frame	Through 12 weeks

Outcome Measure Data

Analysis Population Description

Response was not evaluable for 2 patients with molecularly evident disease as their samples were hemodilute. Response was not evaluable for 1 patient with molecularly detected disease as their sample was hemodilute.

Arm/Group Title	Morphologically Evident Disease	Molecularly Detected Disease
Arm/Group Description	Cycle 1: All patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle Cycle 2: Patients with bone marrow blast counts < 5% may receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of a 28-day cycle. All other patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle. Cycle 3 and subsequent cycles: All patients will receive 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of the 28-day cycle	Cycle 1: All patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle Cycle 2: Patients with bone marrow blast counts < 5% may receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of a 28-day cycle. All other patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle. Cycle 3 and subsequent cycles: All patients will receive 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of the 28-day cycle
Measure Participants	6	8
Complete remission with incomplete hematologic recovery (CRi)	3 17.6%	2 NaN
Morphologic leukemia free state (mLFS)	0 0%	1 NaN
Stable Disease (SD)	2 11.8%	4 NaN
Progressive disease (PD)	1 5.9%	1 NaN

8. Secondary Outcome

Title	Survival Compared Between Patients With Morphologically Evident Disease Versus Patients With Molecularly Detected Disease at the Time of Enrollment
Description	Morphologically evident disease (>5% blasts by cytomorphology) Molecularly detected disease (disease detected with flow cytometry, cytogenetic, or mutational analysis with ≤ 5% blasts by cytomorphology)
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Morphologically Evident Disease	Molecularly Detected Disease
Arm/Group Description	Cycle 1: All patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle Cycle 2: Patients with bone marrow blast counts < 5% may receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of a 28-day cycle. All other patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle. Cycle 3 and subsequent cycles: All patients will receive 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of the 28-day cycle	Cycle 1: All patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle Cycle 2: Patients with bone marrow blast counts < 5% may receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of a 28-day cycle. All other patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle. Cycle 3 and subsequent cycles: All patients will receive 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of the 28-day cycle
Measure Participants	8	9
Median (95% Confidence Interval) [days]	215	336

9. Secondary Outcome

Title	Response Compared Between Patients With de Novo AML Versus Patients With Secondary AML Versus Patients With Treatment-related AML
Description	-Response will be assessed according to the 2017 European LeukemiaNet (ELN) Acute Myeloid Leukemia (AML) recommendations
Time Frame	Through 12 weeks

Outcome Measure Data

Analysis Population Description

2 patients with de novo AML were not evaluable for this outcome measure because the samples were hemodilute. 1 patient with treatment related AML was not evaluable for this outcome measure because the samples were hemodilute.

Arm/Group Title	Patients With de Novo AML	Patients With Secondary AML	Patients With Treatment Related AML
Arm/Group Description	Cycle 1: All patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle Cycle 2: Patients with bone marrow blast counts < 5% may receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of a 28-day cycle. All other patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle. Cycle 3 and subsequent cycles: All patients will receive 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of the 28-day cycle	Cycle 1: All patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle Cycle 2: Patients with bone marrow blast counts < 5% may receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of a 28-day cycle. All other patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle. Cycle 3 and subsequent cycles: All patients will receive 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of the 28-day cycle	Cycle 1: All patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle Cycle 2: Patients with bone marrow blast counts < 5% may receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of a 28-day cycle. All other patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle. Cycle 3 and subsequent cycles: All patients will receive 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of the 28-day cycle
Measure Participants	6	2	6
Complete remission with incomplete hematologic recovery (CRi)	3 17.6%	0 NaN	2 NaN
Morphologic leukemia free state (mLFS)	0 0%	0 NaN	1 NaN
Stable Disease (SD)	3 17.6%	1 NaN	2 NaN
Progressive disease (PD)	0 0%	1 NaN	1 NaN

10. Secondary Outcome

Title	Survival Compared Between Patients With de Novo AML Versus Patients With Secondary AML Versus Patients With Treatment-related AML
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patients With de Novo AML	Patients With Secondary AML	Patients With Treatment Related AML
Arm/Group Description	Cycle 1: All patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle Cycle 2: Patients with bone marrow blast counts < 5% may receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of a 28-day cycle. All other patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle. Cycle 3 and subsequent cycles: All patients will receive 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of the 28-day cycle	Cycle 1: All patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle Cycle 2: Patients with bone marrow blast counts < 5% may receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of a 28-day cycle. All other patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle. Cycle 3 and subsequent cycles: All patients will receive 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of the 28-day cycle	Cycle 1: All patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle Cycle 2: Patients with bone marrow blast counts < 5% may receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of a 28-day cycle. All other patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle. Cycle 3 and subsequent cycles: All patients will receive 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of the 28-day cycle
Measure Participants	8	2	7
Median (95% Confidence Interval) [days]	246	235	244

11. Secondary Outcome

Title	Response Compared Between Patients With Presence of Cytogenetic Abnormalities in Addition to TP53 Mutations Versus Patients With Absence of Cytogenetic Abnormalities in Addition to TP53 Mutations
Description	-Response will be assessed according to the 2017 European LeukemiaNet (ELN) Acute Myeloid Leukemia (AML) recommendations
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Response was not evaluable for 3 patients with presence of cytogenetic abnormalities in addition to TP53 mutations as their response samples were hemodilute.

Arm/Group Title	Presence of Cytogenetic Abnormalities in Addition to TP53 Mutations	Absence of Cytogenetic Abnormalities in Addition to TP53 Mutations
Arm/Group Description	Cycle 1: All patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle Cycle 2: Patients with bone marrow blast counts < 5% may receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of a 28-day cycle. All other patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle. Cycle 3 and subsequent cycles: All patients will receive 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of the 28-day cycle	Cycle 1: All patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle Cycle 2: Patients with bone marrow blast counts < 5% may receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of a 28-day cycle. All other patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle. Cycle 3 and subsequent cycles: All patients will receive 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of the 28-day cycle
Measure Participants	13	1
Complete remission with incomplete hematologic recovery (CRi)	5 29.4%	0 NaN
Morphologic leukemia free state (mLFS)	1 5.9%	0 NaN
Stable Disease (SD)	5 29.4%	1 NaN
Progressive disease (PD)	2 11.8%	0 NaN

12. Secondary Outcome

Title	Survival Compared Between Patients With Presence of Cytogenetic Abnormalities in Addition to TP53 Mutations Versus Patients With Absence of Cytogenetic Abnormalities in Addition to TP53 Mutations
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Presence of Cytogenetic Abnormalities in Addition to TP53 Mutations	Absence of Cytogenetic Abnormalities in Addition to TP53 Mutations
Arm/Group Description	Cycle 1: All patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle Cycle 2: Patients with bone marrow blast counts < 5% may receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of a 28-day cycle. All other patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle. Cycle 3 and subsequent cycles: All patients will receive 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of the 28-day cycle	Cycle 1: All patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle Cycle 2: Patients with bone marrow blast counts < 5% may receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of a 28-day cycle. All other patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle. Cycle 3 and subsequent cycles: All patients will receive 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of the 28-day cycle
Measure Participants	16	1
Median (95% Confidence Interval) [days]	254	NA

13. Secondary Outcome

Title	Median Number of Hospital Stays
Description	-Document number of hospital days that each participant stays and obtain median for all evaluable participants
Time Frame	During cycles 1 and 2 (60 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Decitabine
Arm/Group Description	Cycle 1: All patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle Cycle 2: Patients with bone marrow blast counts < 5% may receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of a 28-day cycle. All other patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle. Cycle 3 and subsequent cycles: All patients will receive 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of the 28-day cycle
Measure Participants	17
Median (Full Range) [days]	9

Adverse Events

Time Frame	Adverse events were collected from time of consent until 30 days after last dose of therapy (may continue until time of transplantation or disease progression - estimated time of 3-6 months). All-cause mortality was collected from time of consent through completion of follow-up (for 2 years after last dose of decitabine or until the patient is lost to follow-up or dies).
Arm/Group Title	Decitabine
Arm/Group Description	Cycle 1: All patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle Cycle 2: Patients with bone marrow blast counts < 5% may receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of a 28-day cycle. All other patients will receive decitabine 20 mg/m^2 IV infusion per day over one hour on Days 1-10 of a 28-day cycle. Cycle 3 and subsequent cycles: All patients will receive 20 mg/m^2 IV infusion per day over one hour on Days 1-5 of the 28-day cycle
All Cause Mortality
	Decitabine
	Affected / at Risk (%)	# Events
Total	15/17 (88.2%)
Serious Adverse Events
	Decitabine
	Affected / at Risk (%)	# Events
Total	4/17 (23.5%)
Infections and infestations
Bacteremia streptococcus	1/17 (5.9%)
Facial cellulitis	1/17 (5.9%)
Febrile neutropenia	2/17 (11.8%)
Sinusitis	1/17 (5.9%)
Vascular disorders
Thromboembolic event	1/17 (5.9%)
Other (Not Including Serious) Adverse Events
	Decitabine
	Affected / at Risk (%)	# Events
Total	17/17 (100%)
Blood and lymphatic system disorders
Anemia	1/17 (5.9%)
Cardiac disorders
Chest tightness	1/17 (5.9%)
Chest pain - cardiac	1/17 (5.9%)
Heart failure	1/17 (5.9%)
Ear and labyrinth disorders
Ear pain	1/17 (5.9%)
Eye disorders
Diplopia	1/17 (5.9%)
Conjunctivitis	1/17 (5.9%)
Gastrointestinal disorders
Heartburn	1/17 (5.9%)
Abdominal pain	1/17 (5.9%)
Constipation	1/17 (5.9%)
Diarrhea	3/17 (17.6%)
Dyspepsia	1/17 (5.9%)
Gastroesophageal reflux disease	1/17 (5.9%)
Gastrointestinal pain	1/17 (5.9%)
Nausea	3/17 (17.6%)
Oral pain	2/17 (11.8%)
Stomach pain	1/17 (5.9%)
Toothache	1/17 (5.9%)
Vomiting	4/17 (23.5%)
General disorders
Knots	1/17 (5.9%)
Injection site reaction	2/17 (11.8%)
Localized edema - right breast	1/17 (5.9%)
Chills	3/17 (17.6%)
Edema limbs	2/17 (11.8%)
Fatigue	4/17 (23.5%)
Fever	1/17 (5.9%)
Infusion related reaction	1/17 (5.9%)
Non-cardiac chest pain	1/17 (5.9%)
Infections and infestations
Febrile neutropenia	4/17 (23.5%)
Cellulitis on shin	1/17 (5.9%)
Staphylococcus epidermis	1/17 (5.9%)
Thrush	1/17 (5.9%)
Sepsis	1/17 (5.9%)
Upper respiratory infection	2/17 (11.8%)
Investigations
Alanine aminotransferase increased	4/17 (23.5%)
Alkaline phosphatase increased	3/17 (17.6%)
Aspartate aminotransferase increased	4/17 (23.5%)
Blood bilirubin increased	1/17 (5.9%)
Cardiac troponin I increased	1/17 (5.9%)
Creatinine increased	2/17 (11.8%)
Lymphocyte count decreased	9/17 (52.9%)
Neutrophil count decreased	6/17 (35.3%)
Platelet count decreased	5/17 (29.4%)
Weight loss	1/17 (5.9%)
White blood cell decreased	7/17 (41.2%)
Metabolism and nutrition disorders
Acidosis	1/17 (5.9%)
Anorexia	2/17 (11.8%)
Hyperglycemia	2/17 (11.8%)
Hypermagnesemia	1/17 (5.9%)
Hypernatremia	2/17 (11.8%)
Hypoalbuminemia	2/17 (11.8%)
Hypocalcemia	3/17 (17.6%)
Hypokalemia	1/17 (5.9%)
Hypomagnesemia	1/17 (5.9%)
Hyponatremia	5/17 (29.4%)
Hypophosphatemia	1/17 (5.9%)
Musculoskeletal and connective tissue disorders
Hip pain	1/17 (5.9%)
Muscle spasms	1/17 (5.9%)
Shoulder pain	1/17 (5.9%)
Generalized muscle weakness	1/17 (5.9%)
Myalgia	1/17 (5.9%)
Neck pain	1/17 (5.9%)
Nervous system disorders
Dizziness	4/17 (23.5%)
Dysgeusia	1/17 (5.9%)
Headache	3/17 (17.6%)
Peripheral sensory neuropathy	1/17 (5.9%)
Tremor	1/17 (5.9%)
Psychiatric disorders
Confusion	1/17 (5.9%)
Delirium	1/17 (5.9%)
Hallucinations	2/17 (11.8%)
Insomnia	2/17 (11.8%)
Renal and urinary disorders
Acute kidney injury	2/17 (11.8%)
Respiratory, thoracic and mediastinal disorders
Cough	2/17 (11.8%)
Dyspnea	4/17 (23.5%)
Epistaxis	2/17 (11.8%)
Nasal congestion	1/17 (5.9%)
Respiratory failure	3/17 (17.6%)
Sore throat	2/17 (11.8%)
Skin and subcutaneous tissue disorders
Oily skin	1/17 (5.9%)
Traumatic fat necrosis	1/17 (5.9%)
Rash maculopapular	3/17 (17.6%)
Vascular disorders
Hypertension	2/17 (11.8%)
Hypotension	1/17 (5.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.