5-Azacytidine With Lenalidomide in Patients With High Risk Myelodysplastic Syndrome (MDS) and Acute Myelogenous Leukemia (AML)
|ClinicalTrials.gov Identifier: NCT01038635|
Recruitment Status : Completed
First Posted : December 24, 2009
Results First Posted : February 10, 2017
Last Update Posted : February 10, 2017
|First Submitted Date ICMJE||December 23, 2009|
|First Posted Date ICMJE||December 24, 2009|
|Results First Submitted Date||December 19, 2016|
|Results First Posted Date||February 10, 2017|
|Last Update Posted Date||February 10, 2017|
|Start Date ICMJE||December 2009|
|Primary Completion Date||November 2015 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Number of Dose Limiting Toxicities for Determining Maximum Tolerated Dose (MTD) of Lenalidomide in Combination With 5-azacytidine (5-AZA) [ Time Frame: 3-8 week cycles, up to 24 weeks ]
DLT determined only during first course of therapy, at least 28 days from treatment of last participant before a new dose level initiated. All severe (Grade 3-4) non-hematological toxicities that are drug related considered for DLT determination. If 1 participant develops grade III-IV non-hematological toxicity, 3 more will be accrued at that particular dose level. If 2 or more participants develop grade III-IV non-hematologic toxicity, the doses of the combination at which this occurs will be considered too toxic. A total of 10 patients will be treated at the maximally tolerated dose (MTD) of the combination (the dose level below that considered to be too toxic) to confirm its tolerability.
|Original Primary Outcome Measures ICMJE
||Maximum Dose Tolerated (MTD) [ Time Frame: 3-8 week cycles ]|
|Change History||Complete list of historical versions of study NCT01038635 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||5-Azacytidine With Lenalidomide in Patients With High Risk Myelodysplastic Syndrome (MDS) and Acute Myelogenous Leukemia (AML)|
|Official Title ICMJE||Phase I/II Study of the Combination of 5-azacitidine With Lenalidomide in Patients With High Risk Myelodysplastic Syndrome (MDS) and Acute Myelogenous Leukemia (AML)|
The goal of Phase 1 of this clinical research study is to find the highest tolerable dose of lenalidomide that can be given in combination with azacitidine to patients with MDS or AML.
The goal of Phase 2 of this study is to learn if the combination dose of azacitidine and lenalidomide found in Phase 1 can help to control MDS and/or AML.
The safety of this drug combination will be studied in both Phases.
The Study Drugs:
Azacitidine is designed to block certain proteins that stop the function of tumor-fighting genes. By blocking the "bad" proteins, the tumor-fighting genes may be able to work better.
Lenalidomide is designed to change the immune system. It may also interfere with the development of tiny blood vessels that help support tumor growth. Therefore, in theory, it may decrease or prevent the growth of cancer cells.
If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you joined this study. Up to 6 groups of 3-6 participants will be enrolled in the Phase 1 portion of the study, and up to 40 participants will be enrolled in Phase 2.
If you are enrolled in the Phase 1 portion, the dose of lenalidomide you receive will depend on when you joined this study. The first group of participants will receive the lowest dose level of lenalidomide. Each new group will receive a higher dose of lenalidomide than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of lenalidomide is found.
If you are enrolled in the Phase 2 portion, you will receive lenalidomide at the highest dose that was tolerated in the Phase 1 portion.
All participants will receive the same dose level of azacitidine.
Study Drug Administration:
Each study "cycle" will be about 3-8 weeks, depending on how well you tolerate the drugs, any side effects that you may have, and how your blood count and bone marrow recovers.
On Days 1-5 of every cycle, you will receive azacitidine by vein over 15-30 minutes.
In order to participate in this study you must register into and follow the requirements of the Revlimid REMS™ program of Celgene Corporation. This program provides education and counseling on the risks of fetal exposure, blood clots and reduced blood counts. You will be required to receive counseling every 28 days during treatment with lenalidomide, follow the pregnancy testing and birth control requirements of the program that are appropriate for you and take telephone surveys regarding your compliance with the program.
If you are enrolled in Phase 2 of the study, on Days 6-15 of every cycle, you will take capsules of lenalidomide by mouth.
You should swallow lenalidomide capsules whole with a cup (about 8 ounces) of water at the same time each day. Do not break, chew, or open the capsules. If you miss a dose of lenalidomide, take it as soon as you remember on the same day. If you miss taking your dose for the entire day, take your regular dose the next scheduled day (do NOT take double your regular dose to make up for the missed dose). If you take more than the prescribed dose of lenalidomide, you should seek emergency medical care if needed and contact study staff right away. Any unused lenalidomide should be returned as instructed through the RevAssist® program.
Any woman who can become pregnant should wear gloves if touching the lenalidomide capsules.
You have been informed of the risk of birth defects. If you are female, you agree not to become pregnant while taking lenalidomide. For this reason, lenalidomide is provided to patients under a special distribution program called Revlimid REMSTM.
Your dose of study drugs may be lowered if you experience side effects.
You may be given drugs to help prevent side effects, such as nausea, vomiting, and/or diarrhea. The doctor will tell you more about what drugs you may receive.
At every study visit, you will be asked about any other drugs and/or treatments you may be receiving and about any side effects you may be having.
One (1) time during each week of Cycle 1:
On Days 21 and 28 of Cycle 1 (+/- 3 days), you will have a bone marrow aspiration performed to check the status of the disease. You will then have a bone marrow aspiration performed every 7-14 days for the rest of the study. If at any point the disease appears to go into remission, you will then have a bone marrow aspiration performed every 1-3 cycles.
Before Day 1 of Cycles 2 and beyond:
If you are a woman who is able to become pregnant, you will have blood (about 1-2 tablespoons) or urine pregnancy tests 1 time a week for the first 4 weeks of the study, then every 4 weeks while on study, when you stop the study, and 4 weeks after you are off study.
If you are a woman who is able to become pregnant and your menstrual cycles are irregular, you will have blood (about 1-2 tablespoons) or urine pregnancy test 1 time a week for the first 4 weeks, then every 2 weeks while on study, when you stop the study, and 2 and 4 weeks after you are off study.
Length of Study:
You may continue to receive azacitidine as long as the doctor thinks it is in your best interest. You may receive lenalidomide as part of this study for as long as you are benefitting. You will be taken off study if the disease gets worse or you experience intolerable side effects.
This is an investigational study. Both azacitidine and lenalidomide are FDA approved and commercially available for the treatment of MDS. Azacitidine is not FDA approved or commercially available for treatment of AML. The combination as used in this study is investigational.
Up to 88 participants will take part in this study. All will be enrolled at MD Anderson.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 1
|Study Design ICMJE||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Study Arms||Experimental: 5-Azacytidine + Lenalidomide
5-Azacytidine 75 mg/m^2 by vein daily x 5 days on days 1 to 5. Lenalidomide starting dose 10 mg orally daily x 5 days on days 6 to 10.
|Publications *||DiNardo CD, Daver N, Jabbour E, Kadia T, Borthakur G, Konopleva M, Pemmaraju N, Yang H, Pierce S, Wierda W, Bueso-Ramos C, Patel KP, Cortes JE, Ravandi F, Kantarjian HM, Garcia-Manero G. Sequential azacitidine and lenalidomide in patients with high-risk myelodysplastic syndromes and acute myeloid leukaemia: a single-arm, phase 1/2 study. Lancet Haematol. 2015 Jan;2(1):e12-20. doi: 10.1016/S2352-3026(14)00026-X. Epub 2014 Dec 22.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Completion Date||November 2015|
|Primary Completion Date||November 2015 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages||Child, Adult, Senior|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT01038635|
|Other Study ID Numbers ICMJE||2009-0467
NCI-2011-01941 ( Registry Identifier: NCI CTRP )
|Has Data Monitoring Committee||No|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||M.D. Anderson Cancer Center|
|Study Sponsor ICMJE||M.D. Anderson Cancer Center|
|PRS Account||M.D. Anderson Cancer Center|
|Verification Date||December 2016|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP