Acute Myeloid LeukemiaNCT02863458
DNA Hypomethylating Agents and Lenalidomide in Elderly Patients With Myeloid Malignancies in the US
An observational study of Acute Myeloid Leukemia and Myelodysplastic Syndromes, run by The Cleveland Clinic at 1 site in United States.
Trial summary
The study aims to comprehensively analyze data from a large and unselected older AML population in the US, both treated and untreated. These data will widen understanding of treatment decisions for the older Acute Myeloid Leukemia (AML) population. Read more about this study
- Who is it for?
- Ages 66 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, Myelodysplastic Syndromes
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2018to 30 Sep 2020
- How long will I take part?
- 12 Years
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 66 years and older
- All sexes
- No healthy volunteers
- Older adult
Study population: The overall sample will include cases of MDS and AML newly diagnosed between 2001 and 2011 with claims from 2000 to 2012. Investigators estimate this will include approximately 50,000 patients. To allow adequate time for HMA usage to begin to stabilize, our analysis will be restricted to patients alive at least 3 months after its approval. Decitabine received FDA approval for all subtypes of MDS in June 2006, but it was not covered by Medicare initially, so our analysis of it will be restricted to patients who were alive in January 2007. Patients will be followed from the date of their first MDS claim (index date) through death or study end, whichever occurred first.
Who may be able to join
- patients with myeloid malignancies diagnosed during 2001-2011 at the age of 66 years or older
- alive in September 2004 (i.e. 3 months after FDA approval of azacitidine for MDS)
- known month of diagnosis, and not identified from death certificates or autopsy only
- continuous Medicare Part A and B coverage, and were not enrolled in a health maintenance organization during the period of interest
Who cannot join
- Anyone under 66 years
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effectiveness of DNA Hypomethylating Agents and Lenalidomide in Elderly Patients With Myeloid Malignancies in the United States
The study aims to comprehensively analyze data from a large and unselected older AML population in the US, both treated and untreated. These data will widen understanding of treatment decisions for the older Acute Myeloid Leukemia (AML) population. Through use of the SEER-Medicare Registry, the effectiveness and impact of HMA treatments as well as the effectiveness of lenalidomide will be studied.
Read the detailed description
This will be the first study to comprehensively analyze data from a large and unselected older AML population in the US, both treated and untreated. These data will widen understanding of treatment decisions for the older AML population and shed light on the impact of HMA in this vulnerable population. The findings from this study will help identify the role of HMA (with its salient features of better tolerability and lesser toxicity) as a new treatment paradigm for older AML patients and enable comparison of outcomes with HMA vs other "conventional" leukemia therapies (intensive chemotherapy, low dose cytarabine or best supportive care). Additionally, with updated SEER-Medicare file carrying Medicare claims through 2013, this study will help analyze several long term outcome measures extending up to eight years for MDS patients treated with lenalidomide. Finally, the effectiveness of HMA in the SEER-Medicare MDS population will be studied by using SEER-Medicare data. This registry includes information on Medicare MDS beneficiaries - a population age cohort that has the highest incidence rates for MDS and a large sample size with absolute MDS cases approaching 40000, making it the largest MDS registry in the world.
The overall sample will include cases of MDS and AML newly diagnosed between 2001 and 2011 with claims from 2000 to 2012. Investigators estimate this will include approximately 50,000 patients.Therefore, the Target Follow Up design looks at patient records over a span of 12 years. Consists of patients with myeloid malignancies diagnosed during 2001-2011 at the age of 66 years or older and alive in September 2004 (i.e. 3 months after FDA approval of azacitidine for MDS), with known month of diagnosis, and not identified from death certificates or autopsy only, who had continuous Medicare Part A and B coverage, and were not enrolled in a health maintenance organization during the period of interest. The overall sample will include cases of MDS and AML newly diagnosed between 2001 and 2011 with claims from 2000 to 2012.
Variables of interest to be collected will include: MDS subtypes, age at diagnosis, sex, race, comorbidities, median household income at the zip code level, treatments (including supportive care) from diagnosis to AML progression, transfusion status, NCI comorbidity index score, response to treatments (using International Working Group criteria), physician characteristics (speciality data),and hospital characteristics (bed size, teaching status, case volume).
- Conditions
- Acute Myeloid Leukemia, Myelodysplastic Syndromes
- Keywords
- MDS, AML, hypomethylating agents (HMA), Surveillance Epidemiology and End Results (SEER)
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants on hypomethylating agents (HMA) and the effectiveness of HMA in the SEER-Medicare MDS population
Study patterns \& determinants of HMA use in SEER-Medicare MDS population: Use of "2+BCBM" to ID registered \& unregistered MDS cases. Map out geographical distribution of HMA use based on MDS patients reclassified by SMMRS, which will yield the proportion of higher-risk (HR) \& lower-risk (LR) patients receiving HMA. Survival times to be analyzed using Cox models with time varying covariates. Predictors to be selected for both types of responses using learning interactions via hierarchical group-lasso regularization \& monotone spline transformations. Utilization of non-parametric random Forest \& random Survival Forest methods to build regression models \& assess goodness of fit \& functional form of the model-based results. Conduction of propensity score analyses of treatment effects as an alternative method for treatment-assignment bias correction. Propensity scores to be calculated using a generalized boosting method as implemented in the R package twang. Computations will be done in R.
Measured: Analaysis restricted to patients alive at least 3 months after HMA approval. Patients will be followed from date of their first MDS claim (index date) through death or study end, whichever occurred first.
Develop predictive models of HMA treatment outcomes using SEER-Medicare data
To develop predictive models of HMA treatment outcomes using SEER-Medicare data: Treatment response analysis will include variables that are extractable from SEER-Medicare files that can be used to infer standard clinical response criteria. The outcome measures will include: 1) the proportion of patients completing an HMA therapeutic-length treatment episode (TTE) [6 cycles = ~6 months]; 2) changes in transfusion dependence; 3) the number of acute hospitalizations during the HMA therapy period; 4) the time from treatment initiation for MDS to progression to AML; and 5) overall survival from the time of HMA initiation.
Measured: Analaysis restricted to patients alive at least 3 months after HMA approval. Patients will be followed from date of their first MDS claim (index date) through death or study end, whichever occurred first.
Secondary outcomes (2)
Effectiveness of lenalidomide in the SEER-Medicare MDS population
An adequate sample size is used to undertake assessment of several variables that affect use of lenalidomide as well as treatment outcomes which aim to analyze (a) prescribing patters of lenalidomide among the low risk (LR)and high risk (HR) MDS with time (from 2006 to 2013) and consistency with clinical guidelines (b) trends in combination therapy (lenalidomide + other MDS therapies) with time (c) determinants of response to lenalidomide - underlying comorbidities, duration of treatment exposure (in terms of number of cycles), concomitant use of azacitidine or other MDS therapies with transfusion status (e) associations between lenalidomide and a variety of outcomes, including survival, progression to AML, secondary solid tumor malignancies and thromboembolic events and (e) differences in lenalidomide use and outcome between MDS Centers of Excellence (using data from MDS Clinical Consortium) versus community setting.
Measured: Analaysis restricted to patients alive at least 3 months after HMA approval. Patients will be followed from date of their first MDS claim (index date) through death or study end, whichever occurred first.
Identify the role of HMA (with its salient features of better tolerability and lesser toxicity) as a new treatment paradigm for older AML patients and enable comparison of outcomes with HMA vs other "conventional" leukemia therapies.
To develop predictive models of HMA treatment outcomes using SEER-Medicare data: Treatment response analysis will include variables that are extractable from SEER-Medicare files that can be used to infer standard clinical response criteria. The outcome measures will include: 1) the proportion of patients completing an HMA therapeutic-length treatment episode (TTE) [6 cycles = ~6 months]; 2) changes in transfusion dependence; 3) the number of acute hospitalizations during the HMA therapy period; 4) the time from treatment initiation for MDS to progression to AML; and 5) overall survival from the time of HMA initiation.
Measured: Analaysis restricted to patients alive at least 3 months after HMA approval. Patients will be followed from date of their first MDS claim (index date) through death or study end, whichever occurred first.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2016 (estimated)
- Study start1 Sep 2018
- Primary completion30 Sep 2020 (estimated)
- Study completion30 Sep 2020 (estimated)
Why it stopped: Study was a data review, no patient recruitment occurred.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by The Cleveland ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 0 participants (actual)
- Target duration
- 12 Years
Sponsor and investigators
- Lead sponsor
- The Cleveland Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- Celgene
- Responsible party
- Sponsor
- Investigators
- Sudipto Mukherjee, MD, MPh, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02863458
- Sponsor's protocol ID
- 15-1066
- Status last verified
- Apr 2019
- First submitted
- 13 Sep 2015
- Last updated
- 13 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: share study data with Celgene and will plan to publish a manuscript upon completion of the study
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effectiveness of DNA Hypomethylating Agents and Lenalidomide in Elderly Patients With Myeloid Malignancies in the United States
- ClinicalTrials.gov ID
- NCT02863458
- Acronym / sponsor ID
- 15-1066
- Conditions
- Acute Myeloid Leukemia, Myelodysplastic Syndromes
- Keywords
- MDS, AML, hypomethylating agents (HMA), Surveillance Epidemiology and End Results (SEER)
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: Study was a data review, no patient recruitment occurred.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- The Cleveland ClinicUniversity, hospital or other
- Collaborators
- Celgene
- Study start
- 1 Sep 2018 (actual)
- Primary completion
- 30 Sep 2020 (estimated)
- Study completion
- 30 Sep 2020 (estimated)
- First posted
- 11 Aug 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study aims to comprehensively analyze data from a large and unselected older AML population in the US, both treated and untreated. These data will widen understanding of treatment decisions for the older Acute Myeloid Leukemia (AML) population. Through use of the SEER-Medicare Registry, the effectiveness and impact of HMA treatments as well as the effectiveness of lenalidomide will be studied.
Detailed description
This will be the first study to comprehensively analyze data from a large and unselected older AML population in the US, both treated and untreated. These data will widen understanding of treatment decisions for the older AML population and shed light on the impact of HMA in this vulnerable population. The findings from this study will help identify the role of HMA (with its salient features of better tolerability and lesser toxicity) as a new treatment paradigm for older AML patients and enable comparison of outcomes with HMA vs other "conventional" leukemia therapies (intensive chemotherapy, low dose cytarabine or best supportive care). Additionally, with updated SEER-Medicare file carrying Medicare claims through 2013, this study will help analyze several long term outcome measures extending up to eight years for MDS patients treated with lenalidomide. Finally, the effectiveness of HMA in the SEER-Medicare MDS population will be studied by using SEER-Medicare data. This registry includes information on Medicare MDS beneficiaries - a population age cohort that has the highest incidence rates for MDS and a large sample size with absolute MDS cases approaching 40000, making it the largest MDS registry in the world.
The overall sample will include cases of MDS and AML newly diagnosed between 2001 and 2011 with claims from 2000 to 2012. Investigators estimate this will include approximately 50,000 patients.Therefore, the Target Follow Up design looks at patient records over a span of 12 years. Consists of patients with myeloid malignancies diagnosed during 2001-2011 at the age of 66 years or older and alive in September 2004 (i.e. 3 months after FDA approval of azacitidine for MDS), with known month of diagnosis, and not identified from death certificates or autopsy only, who had continuous Medicare Part A and B coverage, and were not enrolled in a health maintenance organization during the period of interest. The overall sample will include cases of MDS and AML newly diagnosed between 2001 and 2011 with claims from 2000 to 2012.
Variables of interest to be collected will include: MDS subtypes, age at diagnosis, sex, race, comorbidities, median household income at the zip code level, treatments (including supportive care) from diagnosis to AML progression, transfusion status, NCI comorbidity index score, response to treatments (using International Working Group criteria), physician characteristics (speciality data),and hospital characteristics (bed size, teaching status, case volume).
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Target follow-up
- 12 Years
Who may qualify
- Ages
- 66 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
- Study population
- The overall sample will include cases of MDS and AML newly diagnosed between 2001 and 2011 with claims from 2000 to 2012. Investigators estimate this will include approximately 50,000 patients. To allow adequate time for HMA usage to begin to stabilize, our analysis will be restricted to patients alive at least 3 months after its approval. Decitabine received FDA approval for all subtypes of MDS in June 2006, but it was not covered by Medicare initially, so our analysis of it will be restricted to patients who were alive in January 2007. Patients will be followed from the date of their first MDS claim (index date) through death or study end, whichever occurred first.
Key inclusion criteria (4 listed)
- patients with myeloid malignancies diagnosed during 2001-2011 at the age of 66 years or older
- alive in September 2004 (i.e. 3 months after FDA approval of azacitidine for MDS)
- known month of diagnosis, and not identified from death certificates or autopsy only
- continuous Medicare Part A and B coverage, and were not enrolled in a health maintenance organization during the period of interest
Key exclusion criteria (1 listed)
- Anyone under 66 years
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Number of Participants on hypomethylating agents (HMA) and the effectiveness of HMA in the SEER-Medicare MDS population
Time frame: Analaysis restricted to patients alive at least 3 months after HMA approval. Patients will be followed from date of their first MDS claim (index date) through death or study end, whichever occurred first.
Study patterns \& determinants of HMA use in SEER-Medicare MDS population: Use of "2+BCBM" to ID registered \& unregistered MDS cases. Map out geographical distribution of HMA use based on MDS patients reclassified by SMMRS, which will yield the proportion of higher-risk (HR) \& lower-risk (LR) patients receiving HMA. Survival times to be analyzed using Cox models with time varying covariates. Predictors to be selected for both types of responses using learning interactions via hierarchical group-lasso regularization \& monotone spline transformations. Utilization of non-parametric random Forest \& random Survival Forest methods to build regression models \& assess goodness of fit \& functional form of the model-based results. Conduction of propensity score analyses of treatment effects as an alternative method for treatment-assignment bias correction. Propensity scores to be calculated using a generalized boosting method as implemented in the R package twang. Computations will be done in R.
Develop predictive models of HMA treatment outcomes using SEER-Medicare data
Time frame: Analaysis restricted to patients alive at least 3 months after HMA approval. Patients will be followed from date of their first MDS claim (index date) through death or study end, whichever occurred first.
To develop predictive models of HMA treatment outcomes using SEER-Medicare data: Treatment response analysis will include variables that are extractable from SEER-Medicare files that can be used to infer standard clinical response criteria. The outcome measures will include: 1) the proportion of patients completing an HMA therapeutic-length treatment episode (TTE) [6 cycles = ~6 months]; 2) changes in transfusion dependence; 3) the number of acute hospitalizations during the HMA therapy period; 4) the time from treatment initiation for MDS to progression to AML; and 5) overall survival from the time of HMA initiation.
2 secondary outcomes
Effectiveness of lenalidomide in the SEER-Medicare MDS population
Time frame: Analaysis restricted to patients alive at least 3 months after HMA approval. Patients will be followed from date of their first MDS claim (index date) through death or study end, whichever occurred first.
Identify the role of HMA (with its salient features of better tolerability and lesser toxicity) as a new treatment paradigm for older AML patients and enable comparison of outcomes with HMA vs other "conventional" leukemia therapies.
Time frame: Analaysis restricted to patients alive at least 3 months after HMA approval. Patients will be followed from date of their first MDS claim (index date) through death or study end, whichever occurred first.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2023.
- Individual participant dataSharing planned: Yes. share study data with Celgene and will plan to publish a manuscript upon completion of the study
Related trials for Acute Myeloid Leukemia
RecruitingPhase 1
A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
AML (Acute Myeloid Leukemia)
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
RecruitingPhase 1/2
Venetoclax and CLAG-M for the Treatment of Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms
Acute Biphenotypic Leukemia, Acute Myeloid Leukemia
Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sudipto Mukherjee, MD, MPh principal investigator
The Cleveland Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Acute Myeloid Leukemia and Myelodysplastic Syndromes, run by The Cleveland Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 13 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants on hypomethylating agents (HMA) and the effectiveness of HMA in the SEER-Medicare MDS population (time frame: Analaysis restricted to patients alive at least 3 months after HMA approval. Patients will be followed from date of their first MDS claim (index date) through death or study end, whichever occurred first.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2023.