Leukemia, Erythroblastic, AcutePhase 2NCT02497404
Azacytidine Prior to in Vivo T-cell Depleted Allo Stem Cell Transplant for Patients With Myeloid Malignancies in CR
A Phase 2 study testing 5-Azacytidine, Fludarabine and Melphalan in people with Leukemia, Erythroblastic, Acute and Myelodysplastic Syndromes, run by Weill Medical College of Cornell University at 1 site in United States.
Trial summary
The purpose of this study is to determine whether 5-Azacytidine priming before the conditioning regimen for subjects receiving a hematopoietic stem cell transplant is an effective treatment for high risk myeloid malignancies in complete remission (CR). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, Erythroblastic, Acute, Myelodysplastic Syndromes
- What is being tested?
- 5-Azacytidine, Fludarabine and Melphalan
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Feb 2015to 17 Jun 2021
- Phase
- Phase 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologically or cytologically confirmed acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) as specified below:
- Acute myeloid leukemia with poor risk cytogenetics in complete morphologic remission. These include: del (5q)/-5, del (7q)/-7, abn 3q, 9q, 11q, 20q, 21q, 17p, t(6;9), t(9;22) or complex karyotypes (≥ 3 unrelated abnormalities); or
- Acute myeloid leukemia with either Flt-3, TET-2, p53, DNMT3A, or ASXL1 mutation, mutations of genes involved in the chromatin/spliceosome category (EZH2, SRSF2, U2AF1, ZRSR2), BCOR, and RUNX1, as well as MLL rearrangement, EVI1 overexpression in complete morphologic remission; or
- Acute myeloid leukemia with a white blood cell count of greater than or equal to 50,000/mcL at presentation in first complete morphologic remission; or
- Acute myeloid leukemia in first complete morphologic remission, having required more than one course of induction chemotherapy to attain remission status; or
- Acute myeloid leukemia, all types, excluding M3 (Promyelocytic leukemia) in second or higher complete morphologic remission; or
Show all 13Show fewer
- Myelodysplastic syndromes (intermediate-2, high risk and chronic myelomonocytic leukemia (CMML) with bone marrow blasts <5%); or
- Secondary acute myeloid leukemia on the basis of prior MDS or prior myeloproliferative neoplasm (MPN) in complete morphologic remission
- Life expectancy not severely limited by concomitant disease
- Karnofsky Performance Score greater than or equal to 70%.
- Adequate organ function as defined below:
- Serum Bilirubin:<2.0 mg/dL; Alanine Aminotransferase (ALT) (SGPT): <3 x upper limit of normal; Creatinine Clearance:>60 mL/min (eGFR as estimated by the modified Modification of Diet in Renal Disease Study (MDRD) equation)
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Evidence of chronic active hepatitis or cirrhosis
- HIV infection
- Uncontrolled illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant and lactating women are excluded from the study because the risks to an unborn fetus or potential risks in nursing infants are unknown.
- There are no prior therapies or concomitant medications that would render the patients ineligible
Trial locations and contacts
1 site in 1 country.
United States1 site
Weill Cornell Medical College
New York, New York, 10021
About this study
Official title: Epigenetic Priming With 5-Azacytidine Prior to in Vivo T-cell Depleted Allogeneic Stem Cell Transplantation for Patients With High Risk Myeloid Malignancies in Morphologic Remission
The purpose of this study is to determine whether 5-Azacytidine priming before the conditioning regimen for subjects receiving a hematopoietic stem cell transplant is an effective treatment for high risk myeloid malignancies in complete remission (CR).
Read the detailed description
This open label two-step phase II study is designed to determine the safety and efficacy of epigenetic priming with 5-Azacytidine immediately prior to reduced intensity conditioning for an in vivo T-cell depleted hematopoietic stem cell transplantation for high risk myeloid malignancies in complete remission (CR).
Subjects will be given a five day course of subcutaneous 5-azacytidine, followed by a reduced intensity conditioning regimen of fludarabine, melphalan and total body irradiation (TBI) prior to an allogeneic hematopoietic stem cell transplantation from a related or unrelated Human Leukocyte Antigen (HLA) matched donor.
The effect of 5-azacytidine on global gene methylation will be assessed. Evaluations for safety, in particular for graft failure, transplant related mortality and acute graft versus host disease will be made on a weekly basis. Efficacy, as defined by disease free survival, will be evaluated with a bone marrow biopsy at the standard time points, which are one-, three-, six-, and twelve-months after transplant and upon clinical suspicion within regular follow-up visits - weekly for the first 3 months, then biweekly for 3 months, then monthly until one-year post-stem cell transplant. Thereafter, unless otherwise dictated by the clinical scenario, the follow up visits will be every 3 months.
- Being tested
- 5-Azacytidine, Fludarabine, Melphalan, Alemtuzumab, Total Body Irradiation
- Medical subject headings
- Leukemia, Erythroblastic, Acute, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5-AzacytidineDrug
Also called Vidaza
Patients will be given a five day course of subcutaneous 5-azacytidine followed by a reduced intensity conditioning regimen of fludarabine and melphalan with or without total body irradiation prior to an allogeneic hematopoietic stem cell transplantation from a related or unrelated HLA matched donor. 5-Azacytidine 75 mg/m2 subcutaneously daily at the same time on days -11, -10, -9,
-8 and -7. This will be administered on an outpatient basis if possible.
FludarabineDrug
Also called Fludara
Conditioning regimen: Hospital admission will usually take place on the first day of the conditioning regimen. Fludarabine will be given at 40 mg/m2 intravenously daily at the same time over 30 minutes on days -6,-5,-4,-3.
MelphalanDrug
Also called Alkeran
Conditioning regimen: Hospital admission will usually take place on the first day of the conditioning regimen. Melphalan will be given at 140 mg/m2 IV on day -3.
AlemtuzumabDrug
Also called Campath, Lemtrada
Conditioning regimen: Hospital admission will usually take place on the first day of the conditioning regimen. Alemtuzumab will be given at 30 mg subcutaneously on Days -4 and -2 for unrelated donors, and Day -2 for related donors.
Total Body IrradiationRadiation
Also called TBI
Conditioning regimen: Hospital admission will usually take place on the first day of the conditioning regimen. Total Body Irradiation (TBI) will be given at 2 doses of 200 cGy each on one day of the conditioning regimen (between days -6 and -3).
| Study group | Role | What they receive |
|---|---|---|
| 5 Azacytidine | Experimental | Patients will be given a five day course of subcutaneous 5-azacytidine, followed by a reduced intensity conditioning regimen of fludarabine and melphalan with or without total body irradiation prior to an allogeneic hematopoietic stem cell transplantation from a related or unrelated HLA matched donor. Receives: Drug: 5-Azacytidine; Drug: Fludarabine; Drug: Melphalan; Drug: Alemtuzumab; Radiation: Total Body Irradiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease Free Survival at 1 Year Post-transplant
Number of participants without evidence of progression of underlying malignancy for which the transplant was performed, assessed at 1 year post-transplant.
Measured: 1 year post-transplant
Secondary outcomes (8)
Disease Free Survival at 6 Months Post-transplant
Number of participants without evidence of progression of underlying malignancy for which the transplant was performed, assessed at 6 months post-transplant
Measured: 6 months post-transplant
Disease Free Survival at 2 Years Post-transplant
Number of participants without evidence of progression of underlying malignancy for which the transplant was performed, assessed at 2 years post-transplant.
Measured: 2 years post-transplant
Overall Survival at 6 Months Post-transplant
Number of participants alive at 6 months post-transplant
Measured: 6 months post-transplant
Overall Survival at 1 Year Post-Transplant
Number of participants alive at 1 year post-transplant
Measured: 1 year post-transplant
Overall Survival at 2 Years Post-Transplant
Number of participants alive at 2 years post-transplant
Measured: 2 years post-transplant
Graft Failure
Number of patients who experience graft failure, defined as the absence of neutrophil engraftment by Day +21 or a drop in the absolute neutrophil count to <0.3 cells/microL for five consecutive days occurring after initial neutrophil engraftment within the first 3 weeks post-transplantation.
Measured: 21 days post-transplant
Acute Graft-versus-Host Disease (GVHD)
Number of patients who develop acute graft-versus-host disease of any grade.
Measured: 2 years post-transplant
High-Risk Extensive Chronic Graft-versus-Host-Disease
Number of patients who develop high-risk extensive chronic graft-versus-host disease. Extensive chronic GVHD is defined as generalized skin or multiple organ involvement. High risk chronic GVHD is defined as platelet count of less than 100k/microL
Measured: 2 years post-transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2015 (estimated)
- Study start13 Feb 2015
- Primary completion17 Jun 2020
- Study completion17 Jun 2021
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, Erythroblastic, AcuteStudies of the same condition, open and under way.
- More trials run by Weill Medical College of Cornell UniversityThe 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
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Weill Medical College of Cornell University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sebastian Mayer, MD, Principal investigator, Weill Medical College of Cornell University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02497404
- Sponsor's protocol ID
- 1306014009
- Status last verified
- Aug 2021
- First submitted
- 19 Feb 2015
- Last updated
- 22 Sep 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Epigenetic Priming With 5-Azacytidine Prior to in Vivo T-cell Depleted Allogeneic Stem Cell Transplantation for Patients With High Risk Myeloid Malignancies in Morphologic Remission
- ClinicalTrials.gov ID
- NCT02497404
- Acronym / sponsor ID
- 1306014009
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Weill Medical College of Cornell UniversityUniversity, hospital or other
- Study start
- 13 Feb 2015 (actual)
- Primary completion
- 17 Jun 2020 (actual)
- Study completion
- 17 Jun 2021 (actual)
- First posted
- 14 Jul 2015 (estimated)
- Results
- Posted 22 Sep 2021
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 study is to determine whether 5-Azacytidine priming before the conditioning regimen for subjects receiving a hematopoietic stem cell transplant is an effective treatment for high risk myeloid malignancies in complete remission (CR).
Detailed description
This open label two-step phase II study is designed to determine the safety and efficacy of epigenetic priming with 5-Azacytidine immediately prior to reduced intensity conditioning for an in vivo T-cell depleted hematopoietic stem cell transplantation for high risk myeloid malignancies in complete remission (CR).
Subjects will be given a five day course of subcutaneous 5-azacytidine, followed by a reduced intensity conditioning regimen of fludarabine, melphalan and total body irradiation (TBI) prior to an allogeneic hematopoietic stem cell transplantation from a related or unrelated Human Leukocyte Antigen (HLA) matched donor.
The effect of 5-azacytidine on global gene methylation will be assessed. Evaluations for safety, in particular for graft failure, transplant related mortality and acute graft versus host disease will be made on a weekly basis. Efficacy, as defined by disease free survival, will be evaluated with a bone marrow biopsy at the standard time points, which are one-, three-, six-, and twelve-months after transplant and upon clinical suspicion within regular follow-up visits - weekly for the first 3 months, then biweekly for 3 months, then monthly until one-year post-stem cell transplant. Thereafter, unless otherwise dictated by the clinical scenario, the follow up visits will be every 3 months.
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, Drug: Fludarabine, Drug: Melphalan, Drug: Alemtuzumab, Radiation: Total Body IrradiationPatients will be given a five day course of subcutaneous 5-azacytidine, followed by a reduced intensity conditioning regimen of fludarabine and melphalan with or without total body irradiation prior to an allogeneic hematopoietic stem cell transplantation from a related or unrelated HLA matched donor. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Patients must have histologically or cytologically confirmed acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) as specified below:
- Life expectancy not severely limited by concomitant disease
- Karnofsky Performance Score greater than or equal to 70%.
- Adequate organ function as defined below:
- Serum Bilirubin:<2.0 mg/dL; Alanine Aminotransferase (ALT) (SGPT): <3 x upper limit of normal; Creatinine Clearance:>60 mL/min (eGFR as estimated by the modified Modification of Diet in Renal Disease Study (MDRD) equation)
Key exclusion criteria (5 listed)
- Evidence of chronic active hepatitis or cirrhosis
- HIV infection
- Uncontrolled illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant and lactating women are excluded from the study because the risks to an unborn fetus or potential risks in nursing infants are unknown.
- There are no prior therapies or concomitant medications that would render the patients ineligible
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-AzacytidineAlso: VidazaPatients will be given a five day course of subcutaneous 5-azacytidine followed by a reduced intensity conditioning regimen of fludarabine and melphalan with or without total body irradiation prior to an allogeneic hematopoietic stem cell transplantation from a related or unrelated HLA matched donor. 5-Azacytidine 75 mg/m2 subcutaneously daily at the same time on days -11, -10, -9, -8 and -7. This will be administered on an outpatient basis if possible. | Drug | 5 Azacytidine |
| FludarabineAlso: FludaraConditioning regimen: Hospital admission will usually take place on the first day of the conditioning regimen. Fludarabine will be given at 40 mg/m2 intravenously daily at the same time over 30 minutes on days -6,-5,-4,-3. | Drug | 5 Azacytidine |
| MelphalanAlso: AlkeranConditioning regimen: Hospital admission will usually take place on the first day of the conditioning regimen. Melphalan will be given at 140 mg/m2 IV on day -3. | Drug | 5 Azacytidine |
| AlemtuzumabAlso: Campath, LemtradaConditioning regimen: Hospital admission will usually take place on the first day of the conditioning regimen. Alemtuzumab will be given at 30 mg subcutaneously on Days -4 and -2 for unrelated donors, and Day -2 for related donors. | Drug | 5 Azacytidine |
| Total Body IrradiationAlso: TBIConditioning regimen: Hospital admission will usually take place on the first day of the conditioning regimen. Total Body Irradiation (TBI) will be given at 2 doses of 200 cGy each on one day of the conditioning regimen (between days -6 and -3). | Radiation | 5 Azacytidine |
Primary outcome
Disease Free Survival at 1 Year Post-transplant
Time frame: 1 year post-transplant
Number of participants without evidence of progression of underlying malignancy for which the transplant was performed, assessed at 1 year post-transplant.
8 secondary outcomes
Disease Free Survival at 6 Months Post-transplant
Time frame: 6 months post-transplant
Disease Free Survival at 2 Years Post-transplant
Time frame: 2 years post-transplant
Overall Survival at 6 Months Post-transplant
Time frame: 6 months post-transplant
Overall Survival at 1 Year Post-Transplant
Time frame: 1 year post-transplant
Overall Survival at 2 Years Post-Transplant
Time frame: 2 years post-transplant
Graft Failure
Time frame: 21 days post-transplant
Acute Graft-versus-Host Disease (GVHD)
Time frame: 2 years post-transplant
High-Risk Extensive Chronic Graft-versus-Host-Disease
Time frame: 2 years post-transplant
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Sebastian Mayer, MD principal investigator
Weill Medical College of Cornell University
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, Fludarabine and Melphalan in people with Leukemia, Erythroblastic, Acute and Myelodysplastic Syndromes, run by Weill Medical College of Cornell University 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 13 inclusion and 5 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: finished, as of the sponsor's last update on 22 Sep 2021. 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?
Yes. Results are posted in the registry (first posted 22 Sep 2021). 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?
Disease Free Survival at 1 Year Post-transplant (time frame: 1 year post-transplant). 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 22 Sep 2021.