A Phase 2 interventional study of Decitabine and Bone marrow biopsy/aspirate in Acute Myeloid Leukemia and Acute Myeloid Leukemia, Relapsed, Adult, sponsored by Washington University School of Medicine. Terminated at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-06-02.
Sponsored by Washington University School of Medicine · Phase 2, Interventional, and Treatment
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.
5,441 studies on the registry are indexed under Leukemia; 637 are open to participants now.
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Relapsed/refractory AML following 7+3 (or similar cytarabine containing induction chemotherapy for AML) disease detected by one of the following methods:
Bone marrow and organ function as defined below:
Exclusion Criteria:
* 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 · Procedure: Bone marrow biopsy/aspirate · Procedure: Peripheral blood draw · Procedure: Skin biopsy · Procedure: Buccal swab
* 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.
Also known as: 5-aza-2'-deoxycytidine
* 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
-Baseline, Cycle 1 Day 10, Cycle 1 Day 28, Cycle 2 Day 28, Cycle 3 Day 28, and Progression/Relapse
* 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
-Baseline (if skin biopsy declined) and Cycle 2 Day 28
Overall Survival of Participants With TP53 Mutation
* 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
Percentage of Responding TP53 Mutated Patients (CR, CRi)
* 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
Time to Stem Cell Transplant Among Participants Who Are Suitable Candidates for Transplant and Have an Identified Donor
* 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
Median Time to Leukemia Relapse (TTLR) in Non-transplant Patients
-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
Event-free Survival (EFS)
-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
Average Number of Hospital Days
-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)
Response Compared Between Patients With Morphologically Evident Disease Versus Patients With Molecularly Detected Disease at the Time of Enrollment
* 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
Survival Compared Between Patients With Morphologically Evident Disease Versus Patients With Molecularly Detected Disease at the Time of Enrollment
* 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
Response Compared Between Patients With de Novo AML Versus Patients With Secondary AML Versus Patients With Treatment-related AML
-Response will be assessed according to the 2017 European LeukemiaNet (ELN) Acute Myeloid Leukemia (AML) recommendations
Time frame: Through 12 weeks
Survival Compared Between Patients With de Novo AML Versus Patients With Secondary AML Versus Patients With Treatment-related AML
Time frame: 2 years
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
-Response will be assessed according to the 2017 European LeukemiaNet (ELN) Acute Myeloid Leukemia (AML) recommendations
Time frame: 12 weeks
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
Median Number of Hospital Stays
-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)
| Milestone | Decitabine |
|---|---|
| Started | 17 |
| Completed | 3 |
| Not completed | 14 |
| Withdrew: Chose alternative therapy | 3 |
| Withdrew: Death | 2 |
| Withdrew: Disease progression | 4 |
| Withdrew: Physician decision | 5 |
* 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
| days | Decitabine |
|---|---|
| Overall Survival of Participants With TP53 Mutation | 244 (116 to 390) |
* 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)
| Participants | Decitabine |
|---|---|
| Percentage of Responding TP53 Mutated Patients (CR, CRi) | 5 |
* 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.
| days | Decitabine |
|---|---|
| Time to Stem Cell Transplant Among Participants Who Are Suitable Candidates for Transplant and Have an Identified Donor | 117 (77 to 163) |
-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.
| days | Decitabine |
|---|---|
| Median Time to Leukemia Relapse (TTLR) in Non-transplant Patients | 308 (64 to 374) |
-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.
| days | Decitabine |
|---|---|
| Event-free Survival (EFS) | 227 (64 to 354) |
-Document number of hospital days that each participant stays and obtain average for all evaluable participants
| days | Decitabine |
|---|---|
| Average Number of Hospital Days | 10.3 (2 to 28) |
* 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
| Participants | Morphologically Evident Disease | Molecularly Detected Disease |
|---|---|---|
| Complete remission with incomplete hematologic recovery (CRi) | 3 | 2 |
| Morphologic leukemia free state (mLFS) | 0 | 1 |
| Stable Disease (SD) | 2 | 4 |
| Progressive disease (PD) | 1 | 1 |
* Morphologically evident disease (\>5% blasts by cytomorphology) * Molecularly detected disease (disease detected with flow cytometry, cytogenetic, or mutational analysis with ≤ 5% blasts by cytomorphology)
| days | Morphologically Evident Disease | Molecularly Detected Disease |
|---|---|---|
| Survival Compared Between Patients With Morphologically Evident Disease Versus Patients With Molecularly Detected Disease at the Time of Enrollment | 215 (58 to 390) | 336 (61 to 557) |
-Response will be assessed according to the 2017 European LeukemiaNet (ELN) Acute Myeloid Leukemia (AML) recommendations
| Participants | Patients With de Novo AML | Patients With Secondary AML | Patients With Treatment Related AML |
|---|---|---|---|
| Complete remission with incomplete hematologic recovery (CRi) | 3 | 0 | 2 |
| Morphologic leukemia free state (mLFS) | 0 | 0 | 1 |
| Stable Disease (SD) | 3 | 1 | 2 |
| Progressive disease (PD) | 0 | 1 | 1 |
| days | Patients With de Novo AML | Patients With Secondary AML | Patients With Treatment Related AML |
|---|---|---|---|
| Survival Compared Between Patients With de Novo AML Versus Patients With Secondary AML Versus Patients With Treatment-related AML | 246 (106 to 557) | 235 (116 to 354) | 244 (58 to 454) |
-Response will be assessed according to the 2017 European LeukemiaNet (ELN) Acute Myeloid Leukemia (AML) recommendations
| Participants | Presence of Cytogenetic Abnormalities in Addition to TP53 Mutations | Absence of Cytogenetic Abnormalities in Addition to TP53 Mutations |
|---|---|---|
| Complete remission with incomplete hematologic recovery (CRi) | 5 | 0 |
| Morphologic leukemia free state (mLFS) | 1 | 0 |
| Stable Disease (SD) | 5 | 1 |
| Progressive disease (PD) | 2 | 0 |
| days | Presence of Cytogenetic Abnormalities in Addition to TP53 Mutations | Absence of Cytogenetic Abnormalities in Addition to TP53 Mutations |
|---|---|---|
| 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 | 254 (116 to 390) | NA (NA to NA) |
-Document number of hospital days that each participant stays and obtain median for all evaluable participants
| days | Decitabine |
|---|---|
| Median Number of Hospital Stays | 9 (2 to 28) |
Collected over 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).. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Decitabine | 15/17 (88.2%) | 4/17 (23.5%) | 17/17 (100%) |
| Event | Decitabine |
|---|---|
| Febrile neutropeniaInfections and infestations | 2/17 |
| Bacteremia streptococcusInfections and infestations | 1/17 |
| Facial cellulitisInfections and infestations | 1/17 |
| SinusitisInfections and infestations | 1/17 |
| Thromboembolic eventVascular disorders | 1/17 |
| Event | Decitabine |
|---|---|
| Lymphocyte count decreasedInvestigations | 9/17 |
| White blood cell decreasedInvestigations | 7/17 |
| Neutrophil count decreasedInvestigations | 6/17 |
| Platelet count decreasedInvestigations | 5/17 |
| HyponatremiaMetabolism and nutrition disorders | 5/17 |
| Febrile neutropeniaInfections and infestations | 4/17 |
| VomitingGastrointestinal disorders | 4/17 |
| FatigueGeneral disorders | 4/17 |
| Alanine aminotransferase increasedInvestigations | 4/17 |
| Aspartate aminotransferase increasedInvestigations | 4/17 |
| Age, Continuous(years) | Decitabine |
|---|---|
| Median | 61 (43 to 74) |
| Sex: Female, Male(Participants) | Decitabine |
|---|---|
| Female | 6 |
| Male | 11 |
| Ethnicity (NIH/OMB)(Participants) | Decitabine |
|---|---|
| Hispanic or Latino | 0 |
| Not Hispanic or Latino | 17 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | Decitabine |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 1 |
| White | 16 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
| Region of Enrollment(participants) | Decitabine |
|---|---|
| United States | 17 |
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