Acute Myeloid LeukemiaPhase 2NCT01743859
Azacitidine and Lenalidomide for Relapsed and Refractory Patients With Acute Myeloid Leukemia
A Phase 2 study testing Azacitidine, Lenalidomide and Off Therapy in people with Acute Myeloid Leukemia, run by University of Colorado, Denver at 1 site in United States.
Trial summary
The primary objective of this study is to determine the complete remission/complete remission with incomplete recovery of blood counts (CR/CRi) rate for relapsed and refractory acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- Azacitidine, Lenalidomide and Off Therapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Dec 2012to 3 Aug 2016
- 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
- • World Health Organization (WHO)-confirmed AML, other than Acute Promyelocytic Leukemia (APL)
- Age >18 years
- White blood cell count (WBC) at initiation of treatment ≤ 10,000/L
- o If WBC is > 10,000/L patients may be started on an appropriate dose of hydroxyurea (to be determined by the investigators), until WBC < 10,000/L, at which time the hydroxyurea will be discontinued for 12 hours prior to enrollment
- Relapsed or refractory (resistant) disease, as defined by standard criteria21:
- Relapsed: Bone marrow blasts ≥5%; reappearance of blasts in the blood; development of extramedullary disease
Show all 14Show fewer
- Refractory (resistant): Failure to achieve Complete Remission (CR) or complete remission with incomplete recovery of blood counts (CRi) in patients who survive ≥7 days following completion of initial treatment, with evidence of persistent leukemia by blood and/or bone marrow examination
- Failure of at least one prior therapy
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (See Appendix D: ECOG Performance Status Scale)
- Life expectancy > 2 months
- All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist® (RevAssist is a restricted distribution program for receiving lenalidomide)
- Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 million International Units per milliliter (mIU/mL) 10 - 14 days prior to study enrollment and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin two acceptable methods of birth control, one highly effective method and one additional effective method at the same time, at least 28 days before she starts taking lenalidomide. FCBP 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. See Appendix F: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods
- 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
- • Known or suspected hypersensitivity to azacitidine or mannitol
- Patients with advanced malignant hepatic tumors.
- Treatment less than four weeks prior to enrollment with other experimental therapies or antineoplastic agents, with the exception of hydroxyurea
- Inability to swallow or absorb drug
- Prior treatment with lenalidomide for AML
- Active opportunistic infection or treatment for opportunistic infection within four weeks of first day of study drug dosing
Show all 19Show fewer
- New York Heart Association Class III or IV heart failure
- Unstable angina pectoris
- Significant uncontrolled cardiac arrhythmias
- Uncontrolled psychiatric illness that would limit compliance with requirements
- Known Human immunodeficiency virus (HIV) infection
- Graft vs. host disease ≥ grade 2
- Relapse after allogeneic stem cell transplantation prior to post-transplant day 30
- Pregnant or breast feeding females; lactating females must agree not to breast feed while taking lenalidomide
- Other medical or psychiatric illness or organ dysfunction or laboratory abnormality which in the opinion of the investigator would compromise the patient's safety or interfere with data interpretation
- Laboratory abnormalities:
- Either creatinine >2.0 mg/dL or creatinine clearance <30 mL/min
- Total bilirubin > 2 x institutional upper limit of normal (ULN) (unless documented Gilbert's syndrome)
- Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) > 3 x institutional ULN
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Cancer Center
Aurora, Colorado, 80045
About this study
Official title: Sequential Treatment With Azacitidine and Lenalidomide for Relapsed and Refractory Patients With Acute Myeloid Leukemia
The primary objective of this study is to determine the complete remission/complete remission with incomplete recovery of blood counts (CR/CRi) rate for relapsed and refractory acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) patients.
Read the detailed description
AML patients with relapsed and refractory disease have very poor outcomes. Sequential azacitidine and lenalidomide was recently shown by the PI of this study to be well-tolerated and effective in elderly, treatment naïve AML patients. Observations from this study and others that have piloted this combination have suggested that patients who received and failed prior treatments may also respond to this regimen. Therefore, the sequential combination of azacitidine with lenalidomide could potentially improve outcomes for relapsed and refractory AML patients by providing them with a treatment option that is tolerable and potentially clinically synergistic. To determine the efficacy of this combination in this population, we will pilot this phase 2 study.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- Azacitidine, Lenalidomide, Off Therapy
- Keywords
- Myeloid, Leukemia
- Medical subject headings
- Leukemia, Myeloid, Acute, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzacitidineDrug
Also called Vidaza (TM)
Enrolled patients will receive 75 mg/m2 of azacitidine subcutaneously (SC) or intravenously (IV) on days 1-7 alone.
LenalidomideDrug
Also called Revlimid (TM)
Beginning on day 8, patients will receive 50 mg of lenalidomide PO, and will take this daily from day 8 through 28.
Off TherapyOther
2 weeks off therapy, then begin sequence again for 12 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Azacitidine + Lenalidomide + Off Therapy | Experimental | Patients will receive 7 days of azacitidine followed by 3 weeks of lenalidomide. They will then have 2 weeks off therapy, for a maximum of 12 cycles. Receives: Drug: Azacitidine; Drug: Lenalidomide; Other: Off Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Complete Remission or Complete Remission With Incomplete Recovery Blood Counts
Change in baseline to end of study. To be assessed by standard criteria based on bone marrow examination. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Measured: Interim assessment after 18 patients (estimated 2 years) and full assessment after 37 patients (estimated 3-4 years)
Overall Response Rate
Change in baseline to end of study. To be assessed by standard criteria based on bone marrow examination
Measured: Planned assessment after enrollment of all 37 patients (estimated 3-4 years)
Secondary outcomes (5)
Response or Remission Duration
Change in baseline to end of study. To be assessed by standard criteria based on bone marrow examination
Measured: Depending on outcomes, will initiate this assessment after 2 years and will continue until completion of study, estimated at 4 years
Toxicity and SAEs Related to Treatment
Change in baseline to end of study. To be measured based on Common Terminology Criteria for Adverse Events (CTCAE) criteria
Measured: Will begin assessment with first patient and will continue until completion of study, estimated to be 4 years
Overall Survival
Change in baseline to end of study
Measured: Depending on outcomes, will begin assessment at 2 years and will continue until completion of study, estimated to be at four years
Progression-free Survival
Change in baseline to end of study. To be assessed by standard criteria based on bone marrow examination
Measured: Depending on outcomes, will initiate this assessment after 2 years and will continue until completion of study, estimated at 4 years
Determine Biomarkers That Predict Response/Toxicity
Change in baseline to end of study. Planned assessments of methylation changes and other biomarkers. Computational biology modeling used to identify biomarkers and predict response.
Measured: Three years after initiating study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2012 (estimated)
- Study start6 Dec 2012
- Primary completion27 Apr 2016
- Study completion3 Aug 2016
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 Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe 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
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- Celgene
- Responsible party
- Sponsor
- Investigators
- Daniel Pollyea, MD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01743859
- Sponsor's protocol ID
- 12-1283.cc
- Other IDs
- NCI-2012-03191
- Status last verified
- Aug 2019
- First submitted
- 16 Nov 2012
- Last updated
- 8 Oct 2019
- 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 8 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sequential Treatment With Azacitidine and Lenalidomide for Relapsed and Refractory Patients With Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT01743859
- Acronym / sponsor ID
- 12-1283.cc
- Conditions
- Acute Myeloid Leukemia
- Keywords
- Myeloid, Leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- Celgene
- Study start
- 6 Dec 2012 (actual)
- Primary completion
- 27 Apr 2016 (actual)
- Study completion
- 3 Aug 2016 (actual)
- First posted
- 6 Dec 2012 (estimated)
- Results
- Posted 8 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 primary objective of this study is to determine the complete remission/complete remission with incomplete recovery of blood counts (CR/CRi) rate for relapsed and refractory acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) patients.
Detailed description
AML patients with relapsed and refractory disease have very poor outcomes. Sequential azacitidine and lenalidomide was recently shown by the PI of this study to be well-tolerated and effective in elderly, treatment naïve AML patients. Observations from this study and others that have piloted this combination have suggested that patients who received and failed prior treatments may also respond to this regimen. Therefore, the sequential combination of azacitidine with lenalidomide could potentially improve outcomes for relapsed and refractory AML patients by providing them with a treatment option that is tolerable and potentially clinically synergistic. To determine the efficacy of this combination in this population, we will pilot this phase 2 study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Azacitidine + Lenalidomide + Off Therapy | Experimental | Drug: Azacitidine, Drug: Lenalidomide, Other: Off TherapyPatients will receive 7 days of azacitidine followed by 3 weeks of lenalidomide. They will then have 2 weeks off therapy, for a maximum of 12 cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- • World Health Organization (WHO)-confirmed AML, other than Acute Promyelocytic Leukemia (APL)
- o If WBC is > 10,000/L patients may be started on an appropriate dose of hydroxyurea (to be determined by the investigators), until WBC < 10,000/L, at which time the hydroxyurea will be discontinued for 12 hours prior to enrollment
Key exclusion criteria (19 listed)
- • Known or suspected hypersensitivity to azacitidine or mannitol
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 (TM)Enrolled patients will receive 75 mg/m2 of azacitidine subcutaneously (SC) or intravenously (IV) on days 1-7 alone. | Drug | Azacitidine + Lenalidomide + Off Therapy |
| LenalidomideAlso: Revlimid (TM)Beginning on day 8, patients will receive 50 mg of lenalidomide PO, and will take this daily from day 8 through 28. | Drug | Azacitidine + Lenalidomide + Off Therapy |
| Off Therapy2 weeks off therapy, then begin sequence again for 12 weeks. | Other | Azacitidine + Lenalidomide + Off Therapy |
Primary outcome
Percentage of Participants With Complete Remission or Complete Remission With Incomplete Recovery Blood Counts
Time frame: Interim assessment after 18 patients (estimated 2 years) and full assessment after 37 patients (estimated 3-4 years)
Change in baseline to end of study. To be assessed by standard criteria based on bone marrow examination. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Overall Response Rate
Time frame: Planned assessment after enrollment of all 37 patients (estimated 3-4 years)
Change in baseline to end of study. To be assessed by standard criteria based on bone marrow examination
5 secondary outcomes
Response or Remission Duration
Time frame: Depending on outcomes, will initiate this assessment after 2 years and will continue until completion of study, estimated at 4 years
Toxicity and SAEs Related to Treatment
Time frame: Will begin assessment with first patient and will continue until completion of study, estimated to be 4 years
Overall Survival
Time frame: Depending on outcomes, will begin assessment at 2 years and will continue until completion of study, estimated to be at four years
Progression-free Survival
Time frame: Depending on outcomes, will initiate this assessment after 2 years and will continue until completion of study, estimated at 4 years
Determine Biomarkers That Predict Response/Toxicity
Time frame: Three years after initiating study
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Acute Myeloid Leukemia
RecruitingPhase 1
A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
AML (Acute Myeloid Leukemia)
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
RecruitingPhase 1/2
Venetoclax and CLAG-M for the Treatment of Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms
Acute Biphenotypic Leukemia, Acute Myeloid Leukemia
Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome
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.
Daniel Pollyea, MD principal investigator
University of Colorado, Denver
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, Lenalidomide and Off Therapy in people with Acute Myeloid Leukemia, run by University of Colorado, Denver 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 14 inclusion and 19 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 8 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 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 8 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?
Percentage of Participants With Complete Remission or Complete Remission With Incomplete Recovery Blood Counts (time frame: Interim assessment after 18 patients (estimated 2 years) and full assessment after 37 patients (estimated 3-4 years)). 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 8 Oct 2019.