Myelodysplastic SyndromePhase 2NCT01556477
The Efficacy of Azacitidine +/- Lenalidomide in High-risk Myelodysplastic Syndrome (MDS)and Acute Myeloid Leukemia (AML) With Del(5q).
A Phase 2 study testing Azacitidine and azacitidine + lenalidomide in people with Myelodysplastic Syndrome and Acute Myelogenous Leukemia, run by Nordic MDS Group at 1 site in Sweden.
Trial summary
The proposed phase II trial is a multicenter, randomized, open-label study that will evaluate the efficacy and safety of azacitidine alone or in combination with lenalidomide in high-risk Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML) with a karyotype including del(5q). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndrome, Acute Myelogenous Leukemia
- What is being tested?
- Azacitidine and azacitidine + lenalidomide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 1 siteSweden
- Study dates
- Mar 2012to Nov 2014
- 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
- 18 years of age at the time of signing the informed consent form.
- MDS with IPSS Int-2 or High with a karyotype including del(5q).
- Acute myeloid leukaemia (AML) with multilineage dysplasia and 20-30 % blasts (former RAEB-t) with a karyotype including del(5q).
- Subject has signed the informed consent form.
- Women of childbearing potential (WCBP) must have a negative serum or urine pregnancy test prior to starting lenalidomide. In addition, sexually active WCBP must agree to use adequate contraceptive methods (oral, injectable, patches, or implantable hormonal contraceptive methods; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) while on lenalidomide. WCBP must agree to have pregnancy tests every 4 weeks while on lenalidomide.
- Males (including those who have had a vasectomy) must use barrier contraception (latex condoms) when engaging in reproductive sexual activity with WCBP while on lenalidomide, when temporarily stopping lenalidomide and 28 days after the last dose of lenalidomide.
- Note: Refractory and relapsed patients can be included as long as they fulfil the inclusion criteria.
Who cannot join
- Eligible for upfront allogeneic SCT without prior induction chemotherapy or azacitidine
- Pregnant or lactating females.
- Prior therapy with azacitidine
- Prior therapy with lenalidomide
- Expected survival less than two months.
- Acute promyelocytic leukemia (APL)
Show all 13Show fewer
- Central nervous system leukemia
- Serum biochemical values as follows
- Serum creatinine >2.0 mg/dL (177 mmol/L)
- Serum aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or alanine transferase (ALT)/serum glutamate pyruvate transaminase (SGPT) >3.0 x upper limit of normal (ULN)
- Serum total bilirubin >1.5 mg/dL
- Prior allergic reaction to thalidomide
- Uncontrolled systemic infection
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Multicentre Open Randomized Phase II Study of the Efficacy and Safety of Azacitidine Alone or in Combination With Lenalidomide in High-risk Myeloid Disease (High-risk Myelodysplastic Syndrome and Acute Myeloid Leukemia) With a Karyotype Including Del(5q)
The proposed phase II trial is a multicenter, randomized, open-label study that will evaluate the efficacy and safety of azacitidine alone or in combination with lenalidomide in high-risk Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML) with a karyotype including del(5q). The primary objective will be to evaluate the efficacy in terms of response according to International Working Group (IWG) criteria for MDS and AML after 6 cycles of azacitidine or azacitidine + lenalidomide treatment, or at end of study if this occurs at an earlier time point.
Read the detailed description
This is an prospective open multi-center randomized phase II study of standard dose azacytidine with or without the addition of lenalidomide in high-risk myeloid disease (high-risk MDS and AML) with a karyotype including del(5q). Seventy-two patients, eligible for treatment with azacytidine (Intermedium/INT-2 and High-risk MDS and AML with 20-30 % marrow blasts according to label) will be included.
Azacytidine will be given in a modified standard dose, azacytidine 5+2 (75 mg/m2/ d subcutaneously for 5 days, followed by a 2-day weekend break, followed by azacytidine 75 mg/m2/ d for 2 days every 28 days, no individual dose exceeding 200 mg) for 6 cycles. Cycle interval may be prolonged if toxicity according to predefined criteria occurs. Patients will be randomized to azacytidine (Arm A) or azacytidine + lenalidomide (Arm B). The initial dose of lenalidomide is 10 mg 21/28 days, starting day 1 in each azacytidine cycle and leaving the last week before start of next azacytidine cycle free. The dose should be increased to 20 mg day 1 in cycle 4 if no toxicity according to predefined criteria occurs. The total study period is 24 weeks + additional weeks caused by prolonged cycle interval. Patients, who following a response may be eligible for allo-SCT may exit the study after cycle 3, 4 or 5 and then be subject to end-of-study assessment. Patients who at start of treatment, or any time during study have a neutrophil count <0,5 x 109/l will be treated with Granulocyte-ColonyStimulatingFactor (G-CSF).
- Being tested
- Azacitidine, azacitidine + lenalidomide
- Keywords
- MDS, AML, Azacitidine, Lenalidomide, del5q
- 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.
AzacitidineDrug
Also called Vidaza
Azacitidine 5-2-2 (75 mg/m2/day subcutaneously for 5 days, followed by a 2-day weekend break, followed by azacitidine 75 mg/m2/ day for 2 days every 28 days, no individual dose exceeding 200 mg) for 6 cycles.
azacitidine + lenalidomideDrug
Also called Vidaza and Revlimid
Azacitidine 5-2-2 (75 mg/m2/day subcutaneously for 5 days, followed by a 2-day weekend break, followed by azacitidine 75 mg/m2/ day for 2 days every 28 days, no individual dose exceeding 200 mg) for 6 cycles.
Initial dose of lenalidomide is 10 mg 21/28 days, starting day 1 in each azacitidine cycle and leaving the last week before start of next azacitidine cycle free. The dose should increased to 25 mg day 1 in cycle 4 if no toxicity according to predefined criteria occurs. Total treatment period is 24 weeks.
| Study group | Role | What they receive |
|---|---|---|
| azacitidine | Active comparator | Not described Receives: Drug: Azacitidine |
| azacitidine + lenalidomide | Experimental | Not described Receives: Drug: azacitidine + lenalidomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response according to IWG criteria for MDS and AML
Response according to IWG criteria include hematologic response (including transfusion independence), bone marrow response (blast count) and cytogenetic response (karyotype) after 6 cycles of azacytidine or azacytidine+lenalidomide. For patients who can keep the 4 week interval the Time Frame will be 25 weeks. The cycle interval can be extended up to 8 weeks which makes 44 weeks the maximum Time Frame.
Measured: 25-44 weeks (after 6 cycles of azacitidine or azacitidine+lenalidomide)
Secondary outcomes (6)
Cytogenetic response after 3 cycles using Fluorescence In Situ Hybridization(FISH)
After 3 cycles the 5q- clone will be measured with FISH to see if there is a response already at that time. For patients who can keep the 4 week interval the Time Frame will be 25 weeks. The cycle interval can be extended up to 8 weeks which makes 44 weeks the maximum Time Frame.
Measured: 25-44 weeks
Safety (number and types of adverse advents) in azacitidine vs azacitidine + lenalidomide groups
Heamtological adverse events will be monitored by checking Hemoglobin,Leucocyte count, Platelet and a Differential every week. Non-Hematological adverse events will be monitored and reported in the Case report form (CRF). For patients who can keep the 4 week interval the Time Frame will be 25 weeks. The cycle interval can be extended up to 8 weeks which makes 44 weeks the maximum Time Frame.
Measured: 25-44 weeks
Azacitidine cycle interval between groups
For patients who can keep the 4 week interval the Time Frame will be 25 weeks. The cycle interval can be extended up to 8 weeks which makes 44 weeks the maximum Time Frame.
Measured: 25-44 weeks
Survival in azacitidine vs azacitidine + lenalidomide groups
All patients will undergo follow-up once yearly from start of treatment; week 52, 104, and 156.
Measured: Up to week 156
Relapse in azacitidine vs azacitidine + lenalidomide groups
All patients will undergo follow-up once yearly from start of treatment; week 52, 104, and 156.
Measured: Up to week 156
Analysis of a broad spectrum of molecular and cellular events which previously have been identified as related to MDS with del(5q).
Bone marrow will be biobanked at inclusion and after 6 cycles of treatment or or at end of study if this occurs at an earlier time point. For patients who can keep the 4 week interval the Time Frame will be 25 weeks. The cycle interval can be extended up to 8 weeks which makes 44 weeks the maximum Time Frame.
Measured: 25-44 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2012 (estimated)
- Study startMar 2012
- Primary completionJul 2014 (estimated)
- Study completionNov 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Myelodysplastic SyndromeStudies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 72 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nordic MDS Group
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Lars Möllgård, MD, PhD, Principal investigator, Nordic MDS Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01556477
- Sponsor's protocol ID
- NMDSG10B
- Other IDs
- 2011-001639-21
- Status last verified
- Mar 2012
- First submitted
- 12 Mar 2012
- Last updated
- 16 Mar 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Rasmussen B, Nilsson L, Tobiasson M, Jadersten M, Garelius H, Dybedal I, Gronbaek K, Ejerblad E, Lorenz F, Flogegard M, Marcher CW, Cavalier L, Ebeling F, Olsnes AM, Norgaard JM, Saft L, Mollgard L, Hellstrom-Lindberg E, Schlegelberger B, Gohring G. Influence of Cytogenetics on the Outcome of Patients With High-Risk Myelodysplastic Syndrome Including Deletion 5q Treated With Azacitidine With or Without Lenalidomide. Genes Chromosomes Cancer. 2025 Feb;64(2):e70029. doi: 10.1002/gcc.70029.
PubMed 39921387
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicentre Open Randomized Phase II Study of the Efficacy and Safety of Azacitidine Alone or in Combination With Lenalidomide in High-risk Myeloid Disease (High-risk Myelodysplastic Syndrome and Acute Myeloid Leukemia) With a Karyotype Including Del(5q)
- ClinicalTrials.gov ID
- NCT01556477
- Acronym / sponsor ID
- NMDSG10B
- Keywords
- MDS, AML, Azacitidine, Lenalidomide, del5q
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 72 participants (estimated)
- Lead sponsor
- Nordic MDS GroupResearch network
- Study start
- Mar 2012
- Primary completion
- Jul 2014 (estimated)
- Study completion
- Nov 2014 (estimated)
- First posted
- 16 Mar 2012 (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 proposed phase II trial is a multicenter, randomized, open-label study that will evaluate the efficacy and safety of azacitidine alone or in combination with lenalidomide in high-risk Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML) with a karyotype including del(5q). The primary objective will be to evaluate the efficacy in terms of response according to International Working Group (IWG) criteria for MDS and AML after 6 cycles of azacitidine or azacitidine + lenalidomide treatment, or at end of study if this occurs at an earlier time point.
Detailed description
This is an prospective open multi-center randomized phase II study of standard dose azacytidine with or without the addition of lenalidomide in high-risk myeloid disease (high-risk MDS and AML) with a karyotype including del(5q). Seventy-two patients, eligible for treatment with azacytidine (Intermedium/INT-2 and High-risk MDS and AML with 20-30 % marrow blasts according to label) will be included.
Azacytidine will be given in a modified standard dose, azacytidine 5+2 (75 mg/m2/ d subcutaneously for 5 days, followed by a 2-day weekend break, followed by azacytidine 75 mg/m2/ d for 2 days every 28 days, no individual dose exceeding 200 mg) for 6 cycles. Cycle interval may be prolonged if toxicity according to predefined criteria occurs. Patients will be randomized to azacytidine (Arm A) or azacytidine + lenalidomide (Arm B). The initial dose of lenalidomide is 10 mg 21/28 days, starting day 1 in each azacytidine cycle and leaving the last week before start of next azacytidine cycle free. The dose should be increased to 20 mg day 1 in cycle 4 if no toxicity according to predefined criteria occurs. The total study period is 24 weeks + additional weeks caused by prolonged cycle interval. Patients, who following a response may be eligible for allo-SCT may exit the study after cycle 3, 4 or 5 and then be subject to end-of-study assessment. Patients who at start of treatment, or any time during study have a neutrophil count <0,5 x 109/l will be treated with Granulocyte-ColonyStimulatingFactor (G-CSF).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| azacitidine | Active comparator | Drug: Azacitidine |
| azacitidine + lenalidomide | Experimental | Drug: azacitidine + lenalidomide |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 18 years of age at the time of signing the informed consent form.
- MDS with IPSS Int-2 or High with a karyotype including del(5q).
- Acute myeloid leukaemia (AML) with multilineage dysplasia and 20-30 % blasts (former RAEB-t) with a karyotype including del(5q).
- Subject has signed the informed consent form.
- Women of childbearing potential (WCBP) must have a negative serum or urine pregnancy test prior to starting lenalidomide. In addition, sexually active WCBP must agree to use adequate contraceptive methods (oral, injectable, patches, or implantable hormonal contraceptive methods; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) while on lenalidomide. WCBP must agree to have pregnancy tests every 4 weeks while on lenalidomide.
Key exclusion criteria (13 listed)
- Eligible for upfront allogeneic SCT without prior induction chemotherapy or azacitidine
- Pregnant or lactating females.
- Prior therapy with azacitidine
- Prior therapy with lenalidomide
- Expected survival less than two months.
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: VidazaAzacitidine 5-2-2 (75 mg/m2/day subcutaneously for 5 days, followed by a 2-day weekend break, followed by azacitidine 75 mg/m2/ day for 2 days every 28 days, no individual dose exceeding 200 mg) for 6 cycles. | Drug | azacitidine |
| azacitidine + lenalidomideAlso: Vidaza and RevlimidAzacitidine 5-2-2 (75 mg/m2/day subcutaneously for 5 days, followed by a 2-day weekend break, followed by azacitidine 75 mg/m2/ day for 2 days every 28 days, no individual dose exceeding 200 mg) for 6 cycles. Initial dose of lenalidomide is 10 mg 21/28 days, starting day 1 in each azacitidine cycle and leaving the last week before start of next azacitidine cycle free. The dose should increased to 25 mg day 1 in cycle 4 if no toxicity according to predefined criteria occurs. Total treatment period is 24 weeks. | Drug | azacitidine + lenalidomide |
Primary outcome
Response according to IWG criteria for MDS and AML
Time frame: 25-44 weeks (after 6 cycles of azacitidine or azacitidine+lenalidomide)
Response according to IWG criteria include hematologic response (including transfusion independence), bone marrow response (blast count) and cytogenetic response (karyotype) after 6 cycles of azacytidine or azacytidine+lenalidomide. For patients who can keep the 4 week interval the Time Frame will be 25 weeks. The cycle interval can be extended up to 8 weeks which makes 44 weeks the maximum Time Frame.
6 secondary outcomes
Cytogenetic response after 3 cycles using Fluorescence In Situ Hybridization(FISH)
Time frame: 25-44 weeks
Safety (number and types of adverse advents) in azacitidine vs azacitidine + lenalidomide groups
Time frame: 25-44 weeks
Azacitidine cycle interval between groups
Time frame: 25-44 weeks
Survival in azacitidine vs azacitidine + lenalidomide groups
Time frame: Up to week 156
Relapse in azacitidine vs azacitidine + lenalidomide groups
Time frame: Up to week 156
Analysis of a broad spectrum of molecular and cellular events which previously have been identified as related to MDS with del(5q).
Time frame: 25-44 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2012.
- Derived from this study: PubMed 39921387Rasmussen B, Nilsson L, Tobiasson M, Jadersten M, Garelius H, Dybedal I, Gronbaek K, Ejerblad E, Lorenz F, Flogegard M, Marcher CW, Cavalier L, Ebeling F, Olsnes AM, Norgaard JM, Saft L, Mollgard L, Hellstrom-Lindberg E, Schlegelberger B, Gohring G. Influence of Cytogenetics on the Outcome of Patients With High-Risk Myelodysplastic Syndrome Including Deletion 5q Treated With Azacitidine With or Without Lenalidomide. Genes Chromosomes Cancer. 2025 Feb;64(2):e70029. doi: 10.1002/gcc.70029.
- Nordic MDS Group websiteLink provided by the sponsor.
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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.
Lars Möllgård, MD, PhD principal investigator
Nordic MDS Group
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 Azacitidine and azacitidine + lenalidomide in people with Myelodysplastic Syndrome and Acute Myelogenous Leukemia, run by Nordic MDS Group at 1 site in Sweden.
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 7 inclusion and 13 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: status not confirmed, as of the sponsor's last update on 16 Mar 2012. 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 Sweden. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Lars Möllgård, MD, PhD (+46 8 5858 0000, lars.mollgard@karolinska.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response according to IWG criteria for MDS and AML (time frame: 25-44 weeks (after 6 cycles of azacitidine or azacitidine+lenalidomide)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01556477, which also lists 1 linked publication.
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 Mar 2012.