LeukemiaPhase 2NCT01442714
Azacitidine + Lenalidomide Combo in the Elderly With Previously Treated AML & High-Risk MDS
A Phase 2 study testing Azacitidine and Lenalidomide in people with Leukemia and Acute Myeloid Leukemia (AML), run by Stanford University at 1 site in United States.
Trial summary
The purpose of the trial is to study how the elderly patients who have previously undergone treatment for acute myeloid leukemia and high-rRisk myelodysplastic syndromes, respond to a combined treatment with azacitidine and lenalidomide. Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Leukemia, Acute Myeloid Leukemia (AML), Myelodysplastic Syndromes (MDS)
- What is being tested?
- Azacitidine and Lenalidomide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2011to May 2014
- 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 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- acute myeloid leukemia (AML) (according to the WHO 2008 classification):
- De novo
- Secondary AML previously treated with demethylating agents for AML
- Secondary AML previously treated with demethylating agents for MDS
- Secondary AML previously treated with high dose lenalidomide for AML (≥ 25mg)
- High Risk MDS:
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- Del (5q)
- Non-del (5q), previously-treated with lenalidomide.
- Novo or secondary HR-MDS previously treated with demethylating agents
- White blood cell (WBC) ≤ 10,000
- Age ≥ 60
- Not an immediate candidate for allogeneic stem cell transplantation
- Unwilling or unable to receive conventional chemotherapy
- Prior therapy:
- with single agent demethylator (5-Azacitidine or Decitabine)
- with Lenalidomide
- Eastern Cooperative Oncology Group performance status ≤ 2
- Life expectancy > 2 months
- All study participants must be registered into the mandatory RevAssist program
- Willing and able to comply with the requirements of RevAssist
- Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test 10-14 days prior to study enrollment and again within 24 hours of prescribing lenalidomide
- Must commit to either continued abstinence from intercourse or begin two acceptable methods of birth control, at least 28 days before she starts taking lenalidomide.
- Must also agree to ongoing pregnancy testing.
- Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy.
- Willing and able to understand and voluntarily sign a written informed consent
- Able to adhere to the study visit schedule and other protocol requirements
Who cannot join
- Patients with LR-MDS progressing to HR-MDS after low dose lenalidomide or 5-day azacitidine will not be eligible.
- History of intolerance to thalidomide
- -development of erythema nodosum while taking thalidomide or similar drugs
- Known or suspected hypersensitivity to azacitidine or mannitol
- Patients with advanced malignant hepatic tumors.
- Concomitant treatment with other anti-neoplastic agents, with the exception of hydroxyurea
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- Previous participation on the VIREL study with the concomitant use of azacitidine plus lenalidomide.
- Anti-neoplastic treatment less than four weeks prior to enrollment, with the exception of hydroxyurea
- Use of any other experimental drug or therapy within 28 days of baseline
- Inability to swallow or absorb drug
- Active opportunistic infection or treatment for opportunistic infection within four weeks of first day of study drug dosing
- New York Heart Association Class III or IV heart failure
- Unstable angina pectoris
- Uncontrolled cardiac arrhythmia
- Uncontrolled psychiatric illness that would limit compliance with requirements
- Known HIV infection
- Pregnant
- Breast feeding
- Lactating females must agree not to breast feed while taking lenalidomide
- Other medical or psychiatric illness or organ dysfunction or laboratory abnormality
- Laboratory abnormalities:
- Either creatinine ≥ 1.5 mg / dL or creatinine clearance ≤ 50 mL / min
- Total bilirubin >1.5 x institutional ULN
- AST and ALT > 2.5 x institutional ULN
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford University School of Medicine
Stanford, California, 94305
About this study
Official title: Azacitidine Plus Lenalidomide Combination in Elderly Patients With Previously Treated Acute Myeloid Leukemia (AML) & High-Risk Myelodysplastic Syndromes (MDS) (VIREL2 Trial)
The purpose of the trial is to study how the elderly patients who have previously undergone treatment for acute myeloid leukemia and high-rRisk myelodysplastic syndromes, respond to a combined treatment with azacitidine and lenalidomide.
Read the detailed description
This is an open label, single-center, and phase 2 study of the combination of azacitidine with lenalidomide in previously treated elderly patients with acute myeloid leukemia (AML) and/or high-risk myelodysplastic syndrome (MDS) who have failed prior therapy with either a demethylating agent and/or IMIDs. MDS includes Chronic Myeloid Leukemia (CML).
Participants patients will receive azacitidine on the first 7 days followed by lenalidomide. Disease assessments with bone marrow examinations will be performed and if a complete response (CR); Complete remission with incomplete count recovery (CRi); partial response (PR); or stable disease (SD) is documented after 6 total cycles, participants will continue treatment until evidence of disease progression, provided they are tolerating treatment. Participants who have progressive disease or relapsed disease after the 6th cycle will be taken off the study, and participants with excessive toxicity at any time will be taken off the study.
- CR = Less than 5% blasts with no Auer rods, absence of extramedullary disease, absolute neutrophil count (ANC) > 1000/µL, platelets > 100,000/µL, and independence of red cell transfusion)
- CR with incomplete recovery (CRi) = all criteria of a CR with the exception of a platelet count less than 100,000/µL or residual neutropenia (< 1000/µL).
- PR = Meeting all hematologic criteria for CR with an allowance for 5% to 25% bone marrow blasts or decrease of pretreatment bone marrow blast percentage by ≥ 50%.
- SD = Change in bone marrow aspirate blast count within 10% of baseline.
- PD = Progressive / relapsed disease defined as reappearance of blasts in the blood or bone marrow blasts ≥ 5%, and development of extramedullary disease.
- Being tested
- Azacitidine, Lenalidomide
- Medical subject headings
- Leukemia, Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzacitidineDrug
Also called 5-azacytidine, Vidaza
Azacitidine is a chemical analogue of the cytosine nucleoside used in DNA and RNA. Azacitidine is thought to induce antineoplastic activity via two mechanisms; inhibition of DNA methyltransferase at low doses, causing hypomethylation of DNA, and direct cytotoxicity in abnormal hematopoietic cells in the bone marrow through its incorporation into DNA and RNA at high doses, resulting in cell death
LenalidomideDrug
Also called CC-5013, Celgene, Revlimid
Lenalidomide has been used to successfully treat both inflammatory disorders and cancers. In vitro, lenalidomide has three main activities: direct anti-tumor effect, inhibition of angiogenesis, and immunomodulatory role. In vivo, lenalidomide induces tumor cell apoptosis directly and indirectly by inhibition of bone marrow stromal cell support, by anti-angiogenic and anti-osteoclastogenic effects, and by immunomodulatory activity.
| Study group | Role | What they receive |
|---|---|---|
| Azacitidine plus Lenalidomide | Experimental | Patients will receive a single dose of azacitidine 75 mg/m² SC or IV on days 1 to 7, followed by lenalidomide 50 mg PO daily on days 8 to 28 of a 42-day cycle. Receives: Drug: Azacitidine; Drug: Lenalidomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR)
Overall response rate was defined as the sum of Complete Response (CR) + CR with incomplete count recovery (CRi) + Partial Response (PR).
Measured: 203 days
Secondary outcomes (2)
Median Duration of Response
The median duration of response was defined by the median duration of response for participants with Complete Response (CR); CR with incomplete count recovery (CRi); or Partial Response (PR).
Measured: 203 days
Overall Survival
Survival was measured from the 1st day of azacitidine treatment to death from any cause.
Measured: 462 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2011 (estimated)
- Study startAug 2011
- Primary completionMar 2014
- Study completionMay 2014
Why it stopped: Lack of efficacy - Inability to meet the primary response endpoint
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 LeukemiaStudies of the same condition, open and under way.
- More trials run by Stanford 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
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- Celgene Corporation
- Responsible party
- Principal investigator, Bruno C. Medeiros, Stanford University
- Investigators
- Bruno Carneiro de Medeiros, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01442714
- Sponsor's protocol ID
- IRB-21686
- Other IDs
- SU-08122011-8268, HEM0022, VIREL2
- Status last verified
- Dec 2017
- First submitted
- 23 Sep 2011
- Last updated
- 3 Jan 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Azacitidine Plus Lenalidomide Combination in Elderly Patients With Previously Treated Acute Myeloid Leukemia (AML) & High-Risk Myelodysplastic Syndromes (MDS) (VIREL2 Trial)
- ClinicalTrials.gov ID
- NCT01442714
- Acronym / sponsor ID
- IRB-21686
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of efficacy - Inability to meet the primary response endpoint
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- Celgene Corporation
- Study start
- Aug 2011
- Primary completion
- Mar 2014 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 28 Sep 2011 (estimated)
- Results
- Posted 3 Jan 2018
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 the trial is to study how the elderly patients who have previously undergone treatment for acute myeloid leukemia and high-rRisk myelodysplastic syndromes, respond to a combined treatment with azacitidine and lenalidomide.
Detailed description
This is an open label, single-center, and phase 2 study of the combination of azacitidine with lenalidomide in previously treated elderly patients with acute myeloid leukemia (AML) and/or high-risk myelodysplastic syndrome (MDS) who have failed prior therapy with either a demethylating agent and/or IMIDs. MDS includes Chronic Myeloid Leukemia (CML).
Participants patients will receive azacitidine on the first 7 days followed by lenalidomide. Disease assessments with bone marrow examinations will be performed and if a complete response (CR); Complete remission with incomplete count recovery (CRi); partial response (PR); or stable disease (SD) is documented after 6 total cycles, participants will continue treatment until evidence of disease progression, provided they are tolerating treatment. Participants who have progressive disease or relapsed disease after the 6th cycle will be taken off the study, and participants with excessive toxicity at any time will be taken off the study.
- CR = Less than 5% blasts with no Auer rods, absence of extramedullary disease, absolute neutrophil count (ANC) > 1000/µL, platelets > 100,000/µL, and independence of red cell transfusion)
- CR with incomplete recovery (CRi) = all criteria of a CR with the exception of a platelet count less than 100,000/µL or residual neutropenia (< 1000/µL).
- PR = Meeting all hematologic criteria for CR with an allowance for 5% to 25% bone marrow blasts or decrease of pretreatment bone marrow blast percentage by ≥ 50%.
- SD = Change in bone marrow aspirate blast count within 10% of baseline.
- PD = Progressive / relapsed disease defined as reappearance of blasts in the blood or bone marrow blasts ≥ 5%, and development of extramedullary disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Azacitidine plus Lenalidomide | Experimental | Drug: Azacitidine, Drug: LenalidomidePatients will receive a single dose of azacitidine 75 mg/m² SC or IV on days 1 to 7, followed by lenalidomide 50 mg PO daily on days 8 to 28 of a 42-day cycle. |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- acute myeloid leukemia (AML) (according to the WHO 2008 classification):
- High Risk MDS:
- White blood cell (WBC) ≤ 10,000
- Age ≥ 60
- Not an immediate candidate for allogeneic stem cell transplantation
Key exclusion criteria (24 listed)
- Patients with LR-MDS progressing to HR-MDS after low dose lenalidomide or 5-day azacitidine will not be eligible.
- History of intolerance to thalidomide
- -development of erythema nodosum while taking thalidomide or similar drugs
- Known or suspected hypersensitivity to azacitidine or mannitol
- Patients with advanced malignant hepatic tumors.
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: 5-azacytidine, VidazaAzacitidine is a chemical analogue of the cytosine nucleoside used in DNA and RNA. Azacitidine is thought to induce antineoplastic activity via two mechanisms; inhibition of DNA methyltransferase at low doses, causing hypomethylation of DNA, and direct cytotoxicity in abnormal hematopoietic cells in the bone marrow through its incorporation into DNA and RNA at high doses, resulting in cell death | Drug | Azacitidine plus Lenalidomide |
| LenalidomideAlso: CC-5013, Celgene, RevlimidLenalidomide has been used to successfully treat both inflammatory disorders and cancers. In vitro, lenalidomide has three main activities: direct anti-tumor effect, inhibition of angiogenesis, and immunomodulatory role. In vivo, lenalidomide induces tumor cell apoptosis directly and indirectly by inhibition of bone marrow stromal cell support, by anti-angiogenic and anti-osteoclastogenic effects, and by immunomodulatory activity. | Drug | Azacitidine plus Lenalidomide |
Primary outcome
Overall Response Rate (ORR)
Time frame: 203 days
Overall response rate was defined as the sum of Complete Response (CR) + CR with incomplete count recovery (CRi) + Partial Response (PR).
2 secondary outcomes
Median Duration of Response
Time frame: 203 days
Overall Survival
Time frame: 462 Days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jan 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Bruno Carneiro de Medeiros principal investigator
Stanford 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 Azacitidine and Lenalidomide in people with Leukemia and Acute Myeloid Leukemia (AML), run by Stanford 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 26 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: stopped early, as of the sponsor's last update on 3 Jan 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?
Yes. Results are posted in the registry (first posted 3 Jan 2018). 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?
Overall Response Rate (ORR) (time frame: 203 days). 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 3 Jan 2018.