Leukemia, Myeloid, AcutePhase 1/2NCT01747499
Azacitidine in Patients Undergoing Matched Unrelated Stem Cell Transplantation
A Phase 1/2 study testing Azacitidine in people with Leukemia, Myeloid, Acute and Myelodysplastic Syndromes, run by Washington University School of Medicine at 1 site in United States.
Trial summary
The purpose of this phase I/II study is to define the maximum tolerated dose of 5-AzaC and the effect on grade II-IV GvHD when given after matched unrelated donor transplant (MUD). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Precursor Cell Lymphoblastic Leukemia-Lymphoma
- What is being tested?
- Azacitidine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Apr 2013to 24 Dec 2018
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must meet the following criteria within 30 days prior to Day 0 unless otherwise noted.
- Phase I: Diagnosis of any hematological malignancy listed below (excluding myelofibrosis) in remission or with stable minimal residual disease
- Acute myelogenous leukemia (AML) in 1st or subsequent remission or in relapse after any remission
- Acute lymphoblastic leukemia (ALL) in 1st or subsequent remission or in relapse after any remission
- Myelodysplastic syndrome either intermediate 1 or 2, or high risk by the International Prognostic Scoring System
- Chronic myelogenous leukemia (CML) in accelerated or second chronic phase
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- Non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) in 2nd or greater complete remission, partial remission, or refractory relapse
- Chronic lymphocytic leukemia (CLL), Rai Stage 2-4, failing at least 2 prior regimens
- Multiple myeloma (MM), Stage 2-3
- Myeloproliferative disorder or neoplasm
- Phase II: Diagnosis of AML in remission 1 or 2 or a diagnosis of myelodysplastic syndrome either intermediate 1 or 2, or high risk by the International Prognostic Scoring System.
- Patients with MDS must be transplant candidates by current clinical standards.
- Patients who have been treated with hypomethylating agents prior to entering the study are eligible.
- Must have matched unrelated donor (8 of 8 HLA match at A, B, C, and DR loci) by high resolution DNA typing
- Must have donor peripheral blood stem cells mobilized by NMDP standards. No bone marrow donors.
- Must have 2-8 x 10^6 CD34+ cells/kg (recipient weight) infused on Day 0.
- Must have at least one additional aliquot of >=1 x 10^6 CD34/kg cryopreserved cells stored at the time of transplant.
- Must receive a myeloablative or reduced intensity conditioning regimen for SCT as defined by the CIBMTR
- Cyclophosphamide and single dose total body irradiation
- Fludarabine and busulfan
- Fractionated TBI and cyclophosphamide
- Busulfan and cyclophosphamide
- Must be able to receive GVHD prophylaxis with tacrolimus and methotrexate.
- Must be ≥ 18 yrs old and ≤ 70 yrs old. Azacitidine is not approved by the FDA for use in children.
- Must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
- Must have laboratory results indicating:
- Total bilirubin < 2.0 mg/dl, unless a diagnosis of Gilbert's disease
- AST/ALT ≤ 3 X the upper limit of institutional normal
- Serum creatinine ≤ 2.0 mg/dl
- Patient must have ability to understand and willingness to provide written informed consent prior to participation in the study and any related procedures being performed.
- The effects of azacitidine on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because category D agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of childbearing age must have a negative serum pregnancy test (ß-human chorionic gonadotropin) within 72 hours prior to initiating the conditioning regimen and be willing to not become pregnant by using effective contraception while undergoing treatment and for at least 3 months after the last dose of azacitidine.
- Men must be willing not to father a new child while receiving therapy. They must use an effective barrier method of contraception during the study and for 3 months following the last dose.
Who cannot join
- Must not have myelofibrosis or other disease known to prolong neutrophil engraftment to > 28 days after transplant.
- Must not be receiving any other investigational agents within 14 days of first dose of azacitidine (Day 7).
- Must not have myeloablative conditioning as defined below:
- TBI < or = Gy +/- purine analog
- Flu + Cy +/- ATG
- Flu + AraC + Ida
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- Cladribine + AraC
- Total Lymphoid Irradiation + ATG
- Must not receive antithymocyte globulin as part of pre-transplant conditioning regimens. Antithymocyte globulin is excluded due to its potential impact on modulating the incidence of GvHD or GvL.
- Must not have uncontrolled intercurrent illness including ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.
- Must not be pregnant or breastfeeding. Pregnant women are excluded from this study because azacitidine is a Category D agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with azacitidine, breastfeeding should be discontinued if the mother is treated azacitidine. These potential risks may also apply to other agents used in this study.
- Must not have a known or suspected hypersensitivity to azacitidine, mannitol, or compounds of similar composition to azacitidine..
- Must not have an advanced malignant hepatic tumor.
- Must not be HIV, HBV, or HCV positive.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: Phase I/II Trial of Intravenous Azacitidine in Patients Undergoing Matched Unrelated Stem Cell Transplantation
The purpose of this phase I/II study is to define the maximum tolerated dose of 5-AzaC and the effect on grade II-IV GvHD when given after matched unrelated donor transplant (MUD).
- Conditions
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Being tested
- Azacitidine
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzacitidineDrug
Also called Vidaza®, Ladakamycin, 5-AzaC
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Conditioning treatment
Transplant on Day 0
15 mg/m^2 azacitidine Days 7-11
15 mg/m^2 azacitidine Days 35-39
15 mg/m^2 azacitidine Days 63-67
15 mg/m^2 azacitidine Days 91-95 Receives: Drug: Azacitidine |
| Cohort 2 | Experimental | Conditioning treatment
Transplant on Day 0
30 mg/m^2 azacitidine Days 7-11
30 mg/m^2 azacitidine Days 35-39
30 mg/m^2 azacitidine Days 63-67
30 mg/m^2 azacitidine Days 91-95 Receives: Drug: Azacitidine |
| Cohort 3 | Experimental | Conditioning treatment
Transplant on Day 0
37.5 mg/m^2 azacitidine Days 7-11
37.5 mg/m^2 azacitidine Days 35-39
37.5 mg/m^2 azacitidine Days 63-67
37.5 mg/m^2 azacitidine Days 91-95 Receives: Drug: Azacitidine |
| Cohort 4 | Experimental | Conditioning treatment
Transplant on Day 0
45 mg/m^2 azacitidine Days 7-11
45 mg/m^2 azacitidine Days 35-39
45 mg/m^2 azacitidine Days 63-67
45 mg/m^2 azacitidine Days 91-95 Receives: Drug: Azacitidine |
| Phase II Cohort | Experimental | Conditioning treatment
Transplant on Day 0
Dose determined in Phase I - 45 mg/m^2 azacitidine Days 7-11
Dose determined in Phase I - 45 mg/m^2 azacitidine Days 35-39
Dose determined in Phase I - 45 mg/m^2 azacitidine Days 63-67
Dose determined in Phase I - 45 mg/m^2 attitudinize Days 91-95 Receives: Drug: Azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I: to Determine the Maximum Tolerated Dose (MTD) of Azacitidine in Patients Undergoing Matched (8 Out of 8) Unrelated Donor Transplant for Any Hematological Malignancy in Remission or With Stable Disease.
The MTD is defined as the dose level immediately below the dose level at which patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity.
Measured: 28 days
Phase II: Number of Participants With Grades II-IV Acute GvHD
GVHD rate and severity will be assessed based on modified Glucksberg criteria. Grade II-IV and III-IV aGVHD in first 180 days after transplant will be assessed.
Measured: Day +180
Secondary outcomes (5)
Rate of Grades III-IV aGVHD at Day +180.
GVHD rate and severity will be assessed based on modified Glucksberg criteria.
Measured: Day +180
Overall Survival as Measured by Number of Participants Alive at 1 Year After Transplant
Date of transplant to the date of death from any cause.
Measured: One year after transplant
Treatment-related Mortality
Death that results from a transplant procedure-related complication (e.g. infection, organ failure, hemorrhage, GVHD) rather than from relapse of the underlying disease or an unrelated cause.
Measured: Day +140
Number of Participants Who Relapsed Within the First Year of Transplant
Recurrence of the original malignant disease after transplantation. The time to relapse is the time to the first observation of hematologic, radiographic, or cytogenetic changes, which result in characterization as relapse.
Measured: Within the first year of transplant
Rate of Chronic GvHD
Measured: One year after transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2012 (estimated)
- Study start15 Apr 2013
- Primary completion31 Aug 2018
- Study completion24 Dec 2018
Why it stopped: Enrolling 8 more patients would be statistically unlikely that the primary endpoint would be reached (reduce day 180 grade II-IV GVHD rates to 20% or less)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Leukemia, Myeloid, AcuteStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- The Foundation for Barnes-Jewish Hospital, National Cancer Institute (NCI), National Institutes of Health (NIH)
- Responsible party
- Sponsor
- Investigators
- Mark A. Schroeder, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01747499
- Sponsor's protocol ID
- 201303012
- Other IDs
- 1P50CA171963-01A1
- Status last verified
- Sep 2019
- First submitted
- 7 Dec 2012
- Last updated
- 16 Oct 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Trial of Intravenous Azacitidine in Patients Undergoing Matched Unrelated Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT01747499
- Acronym / sponsor ID
- 201303012
- Conditions
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Enrolling 8 more patients would be statistically unlikely that the primary endpoint would be reached (reduce day 180 grade II-IV GVHD rates to 20% or less)
- Enrolment
- 54 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- The Foundation for Barnes-Jewish Hospital, National Cancer Institute (NCI), National Institutes of Health (NIH)
- Study start
- 15 Apr 2013
- Primary completion
- 31 Aug 2018 (actual)
- Study completion
- 24 Dec 2018 (actual)
- First posted
- 11 Dec 2012 (estimated)
- Results
- Posted 16 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this phase I/II study is to define the maximum tolerated dose of 5-AzaC and the effect on grade II-IV GvHD when given after matched unrelated donor transplant (MUD).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: AzacitidineConditioning treatment Transplant on Day 0 15 mg/m^2 azacitidine Days 7-11 15 mg/m^2 azacitidine Days 35-39 15 mg/m^2 azacitidine Days 63-67 15 mg/m^2 azacitidine Days 91-95 |
| Cohort 2 | Experimental | Drug: AzacitidineConditioning treatment Transplant on Day 0 30 mg/m^2 azacitidine Days 7-11 30 mg/m^2 azacitidine Days 35-39 30 mg/m^2 azacitidine Days 63-67 30 mg/m^2 azacitidine Days 91-95 |
| Cohort 3 | Experimental | Drug: AzacitidineConditioning treatment Transplant on Day 0 37.5 mg/m^2 azacitidine Days 7-11 37.5 mg/m^2 azacitidine Days 35-39 37.5 mg/m^2 azacitidine Days 63-67 37.5 mg/m^2 azacitidine Days 91-95 |
| Cohort 4 | Experimental | Drug: AzacitidineConditioning treatment Transplant on Day 0 45 mg/m^2 azacitidine Days 7-11 45 mg/m^2 azacitidine Days 35-39 45 mg/m^2 azacitidine Days 63-67 45 mg/m^2 azacitidine Days 91-95 |
| Phase II Cohort | Experimental | Drug: AzacitidineConditioning treatment Transplant on Day 0 Dose determined in Phase I - 45 mg/m^2 azacitidine Days 7-11 Dose determined in Phase I - 45 mg/m^2 azacitidine Days 35-39 Dose determined in Phase I - 45 mg/m^2 azacitidine Days 63-67 Dose determined in Phase I - 45 mg/m^2 attitudinize Days 91-95 |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (32 listed)
- Patients must meet the following criteria within 30 days prior to Day 0 unless otherwise noted.
- Phase I: Diagnosis of any hematological malignancy listed below (excluding myelofibrosis) in remission or with stable minimal residual disease
- Phase II: Diagnosis of AML in remission 1 or 2 or a diagnosis of myelodysplastic syndrome either intermediate 1 or 2, or high risk by the International Prognostic Scoring System.
- Patients with MDS must be transplant candidates by current clinical standards.
- Patients who have been treated with hypomethylating agents prior to entering the study are eligible.
Key exclusion criteria (14 listed)
- Must not have myelofibrosis or other disease known to prolong neutrophil engraftment to > 28 days after transplant.
- Must not be receiving any other investigational agents within 14 days of first dose of azacitidine (Day 7).
- Must not have myeloablative conditioning as defined below:
- Must not receive antithymocyte globulin as part of pre-transplant conditioning regimens. Antithymocyte globulin is excluded due to its potential impact on modulating the incidence of GvHD or GvL.
- Must not have uncontrolled intercurrent illness including ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.
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 |
|---|---|---|
| AzacitidineAlso: Vidaza®, Ladakamycin, 5-AzaC | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4, Phase II Cohort |
Primary outcome
Phase I: to Determine the Maximum Tolerated Dose (MTD) of Azacitidine in Patients Undergoing Matched (8 Out of 8) Unrelated Donor Transplant for Any Hematological Malignancy in Remission or With Stable Disease.
Time frame: 28 days
The MTD is defined as the dose level immediately below the dose level at which patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity.
Phase II: Number of Participants With Grades II-IV Acute GvHD
Time frame: Day +180
GVHD rate and severity will be assessed based on modified Glucksberg criteria. Grade II-IV and III-IV aGVHD in first 180 days after transplant will be assessed.
5 secondary outcomes
Rate of Grades III-IV aGVHD at Day +180.
Time frame: Day +180
Overall Survival as Measured by Number of Participants Alive at 1 Year After Transplant
Time frame: One year after transplant
Treatment-related Mortality
Time frame: Day +140
Number of Participants Who Relapsed Within the First Year of Transplant
Time frame: Within the first year of transplant
Rate of Chronic GvHD
Time frame: One year after transplant
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Mark A. Schroeder, M.D. principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Azacitidine in people with Leukemia, Myeloid, Acute and Myelodysplastic Syndromes, run by Washington University School of Medicine 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 32 inclusion and 14 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: stopped early, as of the sponsor's last update on 16 Oct 2019. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Yes. Results are posted in the registry (first posted 16 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Phase I: to Determine the Maximum Tolerated Dose (MTD) of Azacitidine in Patients Undergoing Matched (8 Out of 8) Unrelated Donor Transplant for Any Hematological Malignancy in Remission or With Stable Disease. (time frame: 28 days). 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 16 Oct 2019; AzTrials last refreshed its copy on 7 Nov 2026.