Myelodysplastic SyndromePhase 2NCT00795548
Safety Study of 5-Azacitidine and Standard Donor Lymphocyte Infusion (DLI) to Treat Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) Relapsing After Allogeneic Stem Cell Transplantation
A Phase 2 study testing 5-Azacitidine in people with Myelodysplastic Syndrome and Acute Myeloid Leukemia, run by Heinrich-Heine University, Duesseldorf at 6 sites in Germany.
Trial summary
This open label phase-II trial evaluates hematological response of an additional treatment with 5-Azacitidine to common DLI in patients with MDS or AML relapsing after allogeneic stem cell transplantation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndrome, Acute Myeloid Leukemia
- What is being tested?
- 5-Azacitidine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 6 sitesGermany
- Study dates
- Nov 2008to Aug 2011
- 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
- Primary and secondary MDS, AML after MDS, and de novo AML relapsing after allogeneic stem cell transplantation
- Eligibility for Donor Lymphocyte Infusions
- Performance status according to the WHO scale: 0, 1 or 2.
- Adequate renal and liver function: bilirubin < 1.5 times the upper limit of normal and a GFR > 50 ml/min
- Absence of severe cardiovascular disease, i.e., arrhythmias requiring chronic treatment, congestive heart failure (NYHA Class III or IV) or symptomatic ischemic heart disease, where New-York Heart Association (NYHA)
- HIV negative and HBs-Ag negative.
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- Absence of active uncontrolled infection (Septicaemia).
- No prior history or current evidence of central nervous system and psychiatric disorders requiring hospitalization.
- Age at least 18 years.
- Negative pregnancy test for women with reproductive potential.
- Signed written informed consent must be given according to national/local regulations.
Who cannot join
- Have malignant hepatic tumors.
- Severe liver dysfunction CHILD B and C.
- Renal insufficiency with a GFR < 50 ml/min
- Radiation therapy, chemotherapy, or cytotoxic therapy, given to treat conditions other than MDS, AML or applied for conditioning prior allogeneic stemcell transplantation.
- Psychiatric illness that would prevent granting of informed consent.
- Treatment with androgenic hormones during the previous 14 days prior Day 1.
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- Active viral infection with known human immunodeficiency virus (HIV) or viral Hepatitis B or C.
- Hypersensitivity to Mannitol or 5-Azacitidine.
- Treatment with other investigational drugs following relapse after allogeneic stemcell transplantation or ongoing adverse events from previous treatment with investigational drugs regardless of time period.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Germany6 sites
Charite´-Campus Benjamin Franklin, Medizinische Klinik III
Berlin, State of Berlin, 01220
Universitaetsklinikum Dresden, Medizinische Klinik und Poliklinik I
Dresden, Saxony, 01307
Department of Hematology, Oncology and Clinical Immunology, University Hospital Duesseldorf
Düsseldorf, North Rhine-Westphalia, 40225
Klinikum der Johann-Wolfgang-Goethe Universität, Medizinische Klinik II
Frankfurt am Main, Hesse, 60590
Bone Marrow Transplantation Unit, University Hospital Hamburg-Eppendorf
Hamburg, Free and Hanseatic City of Hamburg, 20246
Universitaetsklinik Heidelberg, Medizinische Klinik und Poliklinik V
Heidelberg, Baden-Wurttemberg, 69120
About this study
Official title: Phase-II Trial to Assess the Efficacy and Toxicity of 5-Azacitidine in Addition to Standard DLI for the Treatment of Patients With AML or MDS Relapsing After Allogeneic Stem Cell Transplantation
This open label phase-II trial evaluates hematological response of an additional treatment with 5-Azacitidine to common DLI in patients with MDS or AML relapsing after allogeneic stem cell transplantation.
Read the detailed description
Relapse after allogeneic stem cell transplantation is a major problem in patients with poor prognosis AML or MDS. Donor lymphocyte infusions alone re-induce remission in a minority of these patients, which may be the result of poor differentiation of the leukemic cells. The study drug 5-Aza is effective in AML and MDS.In addition to direct cytotoxicity, it alters gene expression and induces differentiation of leukemic blast cells. Furthermore, DNA-demethylating treatment results in an induction of transcription and cell surface expression of formerly unexpressed KIRs (killer Ig-like receptors) in NK cells, which are involved in the specific recognition of leukemic target cells and who are able to generate a specific graft-versus leukemia effect. The increased expression of MHC class I and II molecules on the surface of the recipient's leukemic cells and the de novo expression of formerly silenced KIR genes in donor NK cells due to treatment with 5-Aza may result in an increased susceptibility of myeloid leukemic cells to the allogeneic graft versus leukemia effect. Therefore, the graft-versus leukemia effect by donor lymphocyte infusions and NK cells from the original donor may be supported by additional therapy with 5-Azacitidine.
- Conditions
- Myelodysplastic Syndrome, Acute Myeloid Leukemia
- Being tested
- 5-Azacitidine
- Keywords
- Myelodysplastic syndrome (MDS), Acute myeloid leukemia (AML), Stem cell transplantation, 5-Azacitidine, Donor lymphocyte infusion, MDS or AML relapsed after stem cell transplantation
- Medical subject headings
- Myelodysplastic Syndromes, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5-AzacitidineDrug
Also called Vidaza
5-Aza will be administered at doses of 100mg/m2 via subcutaneous injection over a period of 5 days. The total amount per treatment cycle, consisting of 5 days, is 500mg/m². Each treatment cycle is repeated every 28 days, with a treatment pause of 23 days between each 5-Aza cycle, to a total of 6 (optional 8 cycles) cycles.
DLI will be transfused on day +34 with a total count of CD3+ cells of DLI 1-5x10E6CD3+/kg bodyweight. In absence of GvHD DLI transfusion is repeated on day +90 with DLI 1-5x10E7CD3+/kg bodyweight and on day +142 with DLI 1-5x10E8CD3+/kg bodyweight. Additional DLI may be given.
| Study group | Role | What they receive |
|---|---|---|
| 5-Azacitidine | Experimental | 5-Azacitidine in addition to standard donor lymphocyte infusions. Receives: Drug: 5-Azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Best response
Measured: within the 6 months of treatment
Secondary outcomes (6)
Safety and Toxicity of 5-Azacitidine for patients relapsing after allo-SCT
Measured: within 3 years
Response rate
Measured: within 6 months
Duration of remissions
Measured: within 3 years
Incidence of acute and chronic GvHD
Measured: 3 years
Achievement of complete chimerism
Measured: 6 month
Toxicity
Measured: wtihin 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2008 (estimated)
- Study startNov 2008
- Primary completionOct 2010
- Study completionAug 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myelodysplastic SyndromeStudies of the same condition, open and under way.
- More trials run by Heinrich-Heine University, DuesseldorfThe 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Heinrich-Heine University, Duesseldorf
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Guido Kobbe, PD Dr., Principal investigator, Department of Hematology, Oncology and Clinical Immunology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00795548
- Sponsor's protocol ID
- AZARELA_HHU_2007
- Status last verified
- Jan 2012
- First submitted
- 20 Nov 2008
- Last updated
- 23 Jan 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase-II Trial to Assess the Efficacy and Toxicity of 5-Azacitidine in Addition to Standard DLI for the Treatment of Patients With AML or MDS Relapsing After Allogeneic Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT00795548
- Acronym / sponsor ID
- AZARELA_HHU_2007
- Conditions
- Myelodysplastic Syndrome, Acute Myeloid Leukemia
- Keywords
- Myelodysplastic syndrome (MDS), Acute myeloid leukemia (AML), Stem cell transplantation, 5-Azacitidine, Donor lymphocyte infusion, MDS or AML relapsed after stem cell transplantation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Heinrich-Heine University, DuesseldorfUniversity, hospital or other
- Study start
- Nov 2008
- Primary completion
- Oct 2010 (actual)
- Study completion
- Aug 2011 (actual)
- First posted
- 21 Nov 2008 (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.
This open label phase-II trial evaluates hematological response of an additional treatment with 5-Azacitidine to common DLI in patients with MDS or AML relapsing after allogeneic stem cell transplantation.
Detailed description
Relapse after allogeneic stem cell transplantation is a major problem in patients with poor prognosis AML or MDS. Donor lymphocyte infusions alone re-induce remission in a minority of these patients, which may be the result of poor differentiation of the leukemic cells. The study drug 5-Aza is effective in AML and MDS.In addition to direct cytotoxicity, it alters gene expression and induces differentiation of leukemic blast cells. Furthermore, DNA-demethylating treatment results in an induction of transcription and cell surface expression of formerly unexpressed KIRs (killer Ig-like receptors) in NK cells, which are involved in the specific recognition of leukemic target cells and who are able to generate a specific graft-versus leukemia effect. The increased expression of MHC class I and II molecules on the surface of the recipient's leukemic cells and the de novo expression of formerly silenced KIR genes in donor NK cells due to treatment with 5-Aza may result in an increased susceptibility of myeloid leukemic cells to the allogeneic graft versus leukemia effect. Therefore, the graft-versus leukemia effect by donor lymphocyte infusions and NK cells from the original donor may be supported by additional therapy with 5-Azacitidine.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 5-Azacitidine | Experimental | Drug: 5-Azacitidine5-Azacitidine in addition to standard donor lymphocyte infusions. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Primary and secondary MDS, AML after MDS, and de novo AML relapsing after allogeneic stem cell transplantation
- Eligibility for Donor Lymphocyte Infusions
- Performance status according to the WHO scale: 0, 1 or 2.
- Adequate renal and liver function: bilirubin < 1.5 times the upper limit of normal and a GFR > 50 ml/min
- Absence of severe cardiovascular disease, i.e., arrhythmias requiring chronic treatment, congestive heart failure (NYHA Class III or IV) or symptomatic ischemic heart disease, where New-York Heart Association (NYHA)
Key exclusion criteria (9 listed)
- Have malignant hepatic tumors.
- Severe liver dysfunction CHILD B and C.
- Renal insufficiency with a GFR < 50 ml/min
- Radiation therapy, chemotherapy, or cytotoxic therapy, given to treat conditions other than MDS, AML or applied for conditioning prior allogeneic stemcell transplantation.
- Psychiatric illness that would prevent granting of informed consent.
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-AzacitidineAlso: Vidaza5-Aza will be administered at doses of 100mg/m2 via subcutaneous injection over a period of 5 days. The total amount per treatment cycle, consisting of 5 days, is 500mg/m². Each treatment cycle is repeated every 28 days, with a treatment pause of 23 days between each 5-Aza cycle, to a total of 6 (optional 8 cycles) cycles. DLI will be transfused on day +34 with a total count of CD3+ cells of DLI 1-5x10E6CD3+/kg bodyweight. In absence of GvHD DLI transfusion is repeated on day +90 with DLI 1-5x10E7CD3+/kg bodyweight and on day +142 with DLI 1-5x10E8CD3+/kg bodyweight. Additional DLI may be given. | Drug | 5-Azacitidine |
Primary outcome
Best response
Time frame: within the 6 months of treatment
6 secondary outcomes
Safety and Toxicity of 5-Azacitidine for patients relapsing after allo-SCT
Time frame: within 3 years
Response rate
Time frame: within 6 months
Duration of remissions
Time frame: within 3 years
Incidence of acute and chronic GvHD
Time frame: 3 years
Achievement of complete chimerism
Time frame: 6 month
Toxicity
Time frame: wtihin 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2012.
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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.
Guido Kobbe, PD Dr. principal investigator
Department of Hematology, Oncology and Clinical Immunology
6 sites 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-Azacitidine in people with Myelodysplastic Syndrome and Acute Myeloid Leukemia, run by Heinrich-Heine University, Duesseldorf at 6 sites in Germany.
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 11 inclusion and 9 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 23 Jan 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Germany. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Best response (time frame: within the 6 months of treatment). 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 23 Jan 2012.