Study of MEK Inhibitor Selumetinib in Combination With Azacitidine in Patients With Higher Risk Chronic Myeloid Neoplasia
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03326310|
Recruitment Status : Recruiting
First Posted : October 31, 2017
Last Update Posted : October 16, 2018
|Condition or disease||Intervention/treatment||Phase|
|Chronic Myeloid Leukemia Myelofibroses||Drug: Azacitidine Drug: Selumetinib||Phase 1|
This is a phase I, open-label, dose-escalation study to determine the MTD of selumetinib when combined with the standard dose of azacitidine. For the purposes of DLT assessment, subjects will be stratified into 2 cohorts- cohort A will include subjects with MDS and MDS/MPN; cohort B will include subjects with myelofibrosis. Dose escalation will proceed independently in each of these cohorts. Determination of MTD will thus also proceed independently within each cohort. Three dose levels of selumetinib are planned for evaluation. Dose escalation will follow a 3+3 study design. Patients will be enrolled sequentially and stratified according to disease type as outlined above. An increased dose level will only open to accrual once at least 3 patients have been treated at the lower dose, followed for the defined DLT observation period (28 days, see section 2.8 below), and the lower dose level has been deemed safe.
The 3+3 dose escalation algorithm will proceed as follows:
- If 0/3 patients develop a DLT at a dose level, escalate to the next dose level.
If 1/3 patients develops a DLT at a dose level, enroll 3 additional patients at that dose level.
- At that dose level, if 1/6 patients develops a DLT, escalate to the next dose level.
- If ≥2/6 patients develop a DLT, that dose level will be determined to be too toxic.
- If 2-3/3 patients develop a DLT at a dose level, that dose level will be determined to be too toxic.
Six patients will be treated at the MTD.
- If the study progresses to dose level 3 with 0/3 patients experiencing a DLT, an additional 3 patients will be enrolled at that dose level to gain additional information regarding toxicity.
- If a dose level is determined to be too toxic and the next lower dose level only included 3 patients, an additional 3 patients will be treated at the lower dose level to confirm tolerability.
- If no patients have a DLT reported at dose level 3, that will be defined as the MTD and the dose will not be escalated above that level.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Study of MEK Inhibitor Selumetinib in Combination With Azacitidine in Patients With Higher Risk Chronic Myeloid Neoplasia: MDS, MDS/MPNs, and Myelofibrosis|
|Actual Study Start Date :||September 4, 2018|
|Estimated Primary Completion Date :||September 4, 2021|
|Estimated Study Completion Date :||September 4, 2023|
Experimental: Azacitidine and selumetinib
Subjects will receive azacitidine subcutaneously on days 1-7. Selumetinib will be administered on days 8-21. Subjects will continue on this schedule in cycles of 28 days duration in the absence of disease progression.
Patients will receive azacitidine 75 mg/m2 as a subcutaneous injection on days 1-7. The dose of azacitidine 75 mg/m2 will remain unchanged, unless a dose reduction is required based on toxicities (dose level -1 = selumetinib 50 mg PO twice daily and azacitidine 50 mg/m2).
Subjects will continue on this schedule in cycles of 28 days duration in the absence of disease progression
Other Name: Vidaza
Patients will receive selumetinib administered by mouth on days 8-21. The starting dose cohort (dose level 1) will receive selumetinib 50 mg PO twice daily on days 8-21. Subsequent planned doses include selumetinib 75 mg PO twice daily (dose level 2) and selumetinib 100 mg PO twice daily (dose level 3). Subsequent dose levels will only be given once the prior dose level has shown acceptable safety.
Subjects will continue on this schedule in cycles of 28 days duration in the absence of disease progression.
Other Name: AZD6244
- Number of patients with adverse events [ Time Frame: Up to 24 months. ]To determine the maximum tolerated dose (MTD) of selumetinib when combined with azacitidine and measure any toxicities that may arise.
- Time to completion of next generation sequencing panel. [ Time Frame: From the start of treatment to the record of patient death from any cause, or 100 months, whichever comes first. ]To assess the feasibility of prospectively screening patients for RAS pathway activating mutations by next generation sequencing at our center in the context of a clinical trial.
- Rate of overall response. [ Time Frame: From the start of treatment to the first record of response, up to 100 months, whichever comes first. ]Calculated by complete response + partial response + hematologic improvement.
- Rate of symptom response. [ Time Frame: From the start of treatment to the first record of symptom response, up to 100 months, whichever comes first. ]
- Rate of overall survival. [ Time Frame: From the start of treatment to the date of death, not to exceed 100 months, whichever comes first. ]
- Rate of progression free survival. [ Time Frame: From the start of treatment to the first record of disease progression or the date of death, not to exceed 100 months, whichever comes first. ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03326310
|Contact: Melissa Fridstein||(773) email@example.com|
|Contact: Olatoyosi Odenike, MDfirstname.lastname@example.org|
|United States, Illinois|
|The University of Chicago||Recruiting|
|Chicago, Illinois, United States, 60637|
|Contact: Melissa Fridstein 773-702-9885 email@example.com|