Acute Myeloid Leukemia (AML)Phase 2UPCI 13-165NCT02204020
Phase II Study of 5-azacytidine Maintenance After Transplant for AML or MDS
A Phase 2 study testing 5-azacytidine (5-aza) maintenance therapy after transplant in people with Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS), run by University of Pittsburgh at 1 site in United States.
Trial summary
Despite improvements in outcomes after Hematopoietic Cell Transplantation (HCT) for Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS), the risk of relapse remains high and is the most common cause of mortality after HCT. Moreover, treatment options for relapse after HCT are limited. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS)
- What is being tested?
- 5-azacytidine (5-aza) maintenance therapy after transplant
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2015to 4 May 2016
- Phase
- Phase 2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age≥18 with MDS or high-risk AML, morphologically confirmed and based on World Health Organization criteria (see below for definition of high-risk AML)*, who are transplant candidates with an available human leukocyte antigen (HLA) -matched sibling or unrelated donor with at least 8/8 match
- Definition of high-risk AML:
- Age≥60 years
- Age<60 years with any of the following:
- Secondary AML
- Poor risk cytogenetics, which include abnormalities of chromosome 3, 5, or 7, trisomy 8, 11q23 abnormalities, t(6;9), 20q-, and complex karyotype
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- Fms-like tyrosine kinase 3 (FLT3) mutation
- Disease status ≥ second complete remission (CR2) at time of HCT
- Detectable disease at time of HCT
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Adequate major organ function, as defined by AST and ALT < 2 x upper limit of normal, total serum bilirubin < 2 x upper limit of normal (unless due to hemolysis or Gilbert's syndrome, then no upper limit), creatinine < 2 x upper limit of normal, unless there is known chronic kidney disease (creatinine must be at baseline for subjects with chronic kidney disease)
- In agreement to use an effective barrier method of birth control to avoid pregnancy during the study and for a minimum of 30 days after study treatment, for all male and female patients who are fertile
Who cannot join
- Uncontrolled, life-threatening infection that is not responding to antimicrobial therapy
- Serum creatinine > 2 x upper limit of normal, unless there is known chronic kidney disease (creatinine must be at baseline for subjects with chronic kidney disease), aspartate aminotransferase (AST),alanine aminotransferase (ALT), or total bilirubin > 2x upper limit of normal
- History of psychiatric disorder which may compromise compliance with the protocol or which does not allow for appropriate informed consent
- Patient may not be receiving any other antineoplastic agents
- Pregnancy
- Concurrent use of any other investigational agents on a clinical trial
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- Prior allogeneic stem cell transplant
- Known hypersensitivity to 5-azacytidine * Prior treatment with 5-azacytidine is allowed
- Post-transplant eligibility and exclusion criteria
- Patients will have to meet the following post-transplant eligibility criteria to initiate treatment:
- In complete response (including complete remission with incomplete blood count recovery and marrow complete response) on bone marrow biopsy for response assessment after HCT (typically day +30)
- Patient is within 30-100 days after HCT
- Absolute neutrophil count (ANC) ≥ 1000/µL, platelet count ≥ 20,000/µL
- ECOG performance status 0-2
- Adequate major organ function, as defined by AST and ALT < 2 x upper limit of normal, total serum bilirubin < 2 x upper limit of normal (unless due to hemolysis or Gilbert's syndrome, then no upper limit), creatinine < 2 x upper limit of normal unless there is known chronic kidney disease (creatinine must be at baseline for subjects with chronic kidney disease)
- In agreement to use an effective barrier method of birth control to avoid pregnancy during the study and for a minimum of 30 days after study treatment, for all male and female patients who are fertile
- Patients may not have any of the following post-transplant exclusion criteria:
- Active grade II-IV acute GVHD, for example requiring treatment with steroids at a dose equivalent to prednisone 1mg/kg daily or higher
- Uncontrolled, life-threatening infection that is not responding to antimicrobial therapy
- Serum creatinine > 2 x upper limit of normal unless there is known chronic kidney disease (creatinine must be at baseline for subjects with chronic kidney disease), aspartate aminotransferase (AST),alanine aminotransferase (ALT), or total bilirubin > 2x upper limit of normal
- History of psychiatric disorder which may compromise compliance with the protocol or which does not allow for appropriate informed consent
- Pregnancy
- Concurrent use of any other investigational agents on a clinical trial
- Known hypersensitivity to 5-azacytidine * Prior treatment with 5-azacytidine is allowed
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15232
About this study
Official title: Phase II Study of 5-azacytidine Maintenance After Allogeneic Hematopoietic Cell Transplantation for High-risk Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS)
Despite improvements in outcomes after Hematopoietic Cell Transplantation (HCT) for Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS), the risk of relapse remains high and is the most common cause of mortality after HCT. Moreover, treatment options for relapse after HCT are limited. Strategies to reduce relapse with maintenance therapy in patients who are at high risk are needed to improve survival. 5-aza is a hypomethylating agent that has shown immune modulating properties that may enhance the graft-versus-leukemia (GVL) effect, including upregulation of tumor-associated antigen and costimulatory molecule expression. Moreover, 5-aza has properties that suggest protection against graft-versus-host disease (GVHD) as well. Preliminary data shows that it is well tolerated and effective in clinical use for the treatment of AML or MDS relapse after HCT, as well as for maintenance therapy. This study will evaluate the use of 5-aza for maintenance after HCT in patients with AML or MDS with risk factors that are associated with a high risk for relapse.
Read the detailed description
Phase II study of 5-aza maintenance after allogeneic Hematopoietic Cell Transplantation (HCT) for high-risk Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS). Early studies indicate 5-aza is a hypomethylating agent that has shown immune modulating properties that may enhance the graft-versus-leukemia (GVL) effect, including upregulation of tumor-associated antigen and costimulatory molecule expression. 5-aza also has properties that suggest protection against graft-versus-host disease (GVHD). The primary objective is to evaluate relapse rate at one year. Secondary objectives will include the incidence of both acute and chronic GVHD as well as relapse-free survival, overall survival and toxicity. Correlatives will be performed to evaluate the effect of 5-aza maintenance on the immune system.
Subjects must be transplant candidates with MDS or high risk characteristics of AML. Subjects are consented, screened, then transplanted. Those showing complete response and no active GVHD after transplant can proceed to maintenance with 5-aza. Bone marrow biopsies are performed for response assessment after transplant as well as every three cycles (1 cycle=28 days) while on treatment. Dosing starts at 32mg/m2 and can be increased every 2 cycles without a serious adverse event (SAE), or reduced per toxicity for up to 12 cycles.
- Being tested
- 5-azacytidine (5-aza) maintenance therapy after transplant
- Keywords
- Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS), allogeneic, 5-azacytidine (5-aza), hematopoietic, transplantation, transplant, graft-versus-tumor, graft-versus-host disease (GVHD), epigenetic, maintenance, hypomethylation, relapse
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Graft vs Host Disease, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5-azacytidine (5-aza) maintenance therapy after transplantDrug
Also called 5-aza
The planned initial dose of 5-aza is 32mg/m2 (Level 0) administered either subcutaneously or intravenously for days 1 through 5 of a 28-day cycle, which will be initiated between day+30 and day+100 after HCT. Patients who tolerate this dose based on hematologic parameters and with no SAEs for two consecutive cycles will be eligible for a dose escalation to 50mg/m2 (Level +1). Patients who tolerate this dose based on the same criteria as above for two consecutive cycles will be eligible for a dose escalation to 75mg/m² (Level +2). Patients will continue at dose Level +2 for the remainder of the study provided there are no toxicities that require dose reduction. Patients requiring a dose reduction are not eligible for re-escalation.
| Study group | Role | What they receive |
|---|---|---|
| 5-azacytidine | Experimental | 5-aza SC or IV 32mg/m2 - 75mg/m2 (based on dose escalation) Receives: Drug: 5-azacytidine (5-aza) maintenance therapy after transplant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Relapse rate at 1 year
Study will evaluate the relapse rate associated with 5-azacytidine (5-aza) as maintenance therapy after HCT in patients with high-risk AML or MDS.
Measured: 3 years
Secondary outcomes (6)
Safety of Toxicity Requiring Treatment Discontinuation (TRTD)
Measured: 3 years
Overall survival
Measured: 3 years
Incidence of acute GVHD
Measured: 3 years
Percentage of Toxicity Requiring Treatment Discontinuation (TRTD)
Measured: 3 years
relapse-free survival
Measured: 3 years
Incidence of chronic GVHD
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2014 (estimated)
- Study startApr 2015
- Primary completionApr 2015
- Study completion4 May 2016
Why it stopped: Lack of interest with investigators - no subjects enrolled
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid Leukemia (AML)Studies of the same condition, open and under way.
- More trials run by University of PittsburghThe 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Annie Im, M.D., University of Pittsburgh
- Investigators
- Annie Im, MD, Principal investigator, University of Pittsburgh Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02204020
- Sponsor's protocol ID
- UPCI 13-165
- Acronym
- UPCI 13-165
- Status last verified
- Mar 2018
- First submitted
- 25 Jul 2014
- Last updated
- 30 Mar 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of 5-azacytidine Maintenance After Allogeneic Hematopoietic Cell Transplantation for High-risk Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS)
- ClinicalTrials.gov ID
- NCT02204020
- Acronym / sponsor ID
- UPCI 13-165 / UPCI 13-165
- Keywords
- Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS), allogeneic, 5-azacytidine (5-aza), hematopoietic, transplantation, transplant, graft-versus-tumor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Lack of interest with investigators - no subjects enrolled
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Study start
- Apr 2015 (actual)
- Primary completion
- Apr 2015 (actual)
- Study completion
- 4 May 2016 (actual)
- First posted
- 30 Jul 2014 (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.
Despite improvements in outcomes after Hematopoietic Cell Transplantation (HCT) for Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS), the risk of relapse remains high and is the most common cause of mortality after HCT. Moreover, treatment options for relapse after HCT are limited. Strategies to reduce relapse with maintenance therapy in patients who are at high risk are needed to improve survival. 5-aza is a hypomethylating agent that has shown immune modulating properties that may enhance the graft-versus-leukemia (GVL) effect, including upregulation of tumor-associated antigen and costimulatory molecule expression. Moreover, 5-aza has properties that suggest protection against graft-versus-host disease (GVHD) as well. Preliminary data shows that it is well tolerated and effective in clinical use for the treatment of AML or MDS relapse after HCT, as well as for maintenance therapy. This study will evaluate the use of 5-aza for maintenance after HCT in patients with AML or MDS with risk factors that are associated with a high risk for relapse.
Detailed description
Phase II study of 5-aza maintenance after allogeneic Hematopoietic Cell Transplantation (HCT) for high-risk Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS). Early studies indicate 5-aza is a hypomethylating agent that has shown immune modulating properties that may enhance the graft-versus-leukemia (GVL) effect, including upregulation of tumor-associated antigen and costimulatory molecule expression. 5-aza also has properties that suggest protection against graft-versus-host disease (GVHD). The primary objective is to evaluate relapse rate at one year. Secondary objectives will include the incidence of both acute and chronic GVHD as well as relapse-free survival, overall survival and toxicity. Correlatives will be performed to evaluate the effect of 5-aza maintenance on the immune system.
Subjects must be transplant candidates with MDS or high risk characteristics of AML. Subjects are consented, screened, then transplanted. Those showing complete response and no active GVHD after transplant can proceed to maintenance with 5-aza. Bone marrow biopsies are performed for response assessment after transplant as well as every three cycles (1 cycle=28 days) while on treatment. Dosing starts at 32mg/m2 and can be increased every 2 cycles without a serious adverse event (SAE), or reduced per toxicity for up to 12 cycles.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 5-azacytidine | Experimental | Drug: 5-azacytidine (5-aza) maintenance therapy after transplant5-aza SC or IV 32mg/m2 - 75mg/m2 (based on dose escalation) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Age≥18 with MDS or high-risk AML, morphologically confirmed and based on World Health Organization criteria (see below for definition of high-risk AML)*, who are transplant candidates with an available human leukocyte antigen (HLA) -matched sibling or unrelated donor with at least 8/8 match
- Age≥60 years
- Age<60 years with any of the following:
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Adequate major organ function, as defined by AST and ALT < 2 x upper limit of normal, total serum bilirubin < 2 x upper limit of normal (unless due to hemolysis or Gilbert's syndrome, then no upper limit), creatinine < 2 x upper limit of normal, unless there is known chronic kidney disease (creatinine must be at baseline for subjects with chronic kidney disease)
Key exclusion criteria (24 listed)
- Uncontrolled, life-threatening infection that is not responding to antimicrobial therapy
- Serum creatinine > 2 x upper limit of normal, unless there is known chronic kidney disease (creatinine must be at baseline for subjects with chronic kidney disease), aspartate aminotransferase (AST),alanine aminotransferase (ALT), or total bilirubin > 2x upper limit of normal
- History of psychiatric disorder which may compromise compliance with the protocol or which does not allow for appropriate informed consent
- Patient may not be receiving any other antineoplastic agents
- Pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 5-azacytidine (5-aza) maintenance therapy after transplantAlso: 5-azaThe planned initial dose of 5-aza is 32mg/m2 (Level 0) administered either subcutaneously or intravenously for days 1 through 5 of a 28-day cycle, which will be initiated between day+30 and day+100 after HCT. Patients who tolerate this dose based on hematologic parameters and with no SAEs for two consecutive cycles will be eligible for a dose escalation to 50mg/m2 (Level +1). Patients who tolerate this dose based on the same criteria as above for two consecutive cycles will be eligible for a dose escalation to 75mg/m² (Level +2). Patients will continue at dose Level +2 for the remainder of the study provided there are no toxicities that require dose reduction. Patients requiring a dose reduction are not eligible for re-escalation. | Drug | 5-azacytidine |
Primary outcome
Relapse rate at 1 year
Time frame: 3 years
Study will evaluate the relapse rate associated with 5-azacytidine (5-aza) as maintenance therapy after HCT in patients with high-risk AML or MDS.
6 secondary outcomes
Safety of Toxicity Requiring Treatment Discontinuation (TRTD)
Time frame: 3 years
Overall survival
Time frame: 3 years
Incidence of acute GVHD
Time frame: 3 years
Percentage of Toxicity Requiring Treatment Discontinuation (TRTD)
Time frame: 3 years
relapse-free survival
Time frame: 3 years
Incidence of chronic GVHD
Time frame: 3 years
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 30 Mar 2018.
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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.
Annie Im, MD principal investigator
University of Pittsburgh Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 5-azacytidine (5-aza) maintenance therapy after transplant in people with Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS), run by University of Pittsburgh 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 12 inclusion and 24 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 30 Mar 2018. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Relapse rate at 1 year (time frame: 3 years). 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 30 Mar 2018.