Trametinib in Treating Patients With Relapsed or Refractory Juvenile Myelomonocytic Leukemia
A Phase 2 Study of the MEK Inhibitor Trametinib (NSC# 763093) in Children With Relapsed or Refractory Juvenile Myelomonocytic Leukemia
4 other identifiers
interventional
10
1 country
57
Brief Summary
This phase II trial studies how well trametinib works in treating patients with juvenile myelomonocytic leukemia that has come back (relapsed) or does not respond to treatment (refractory). Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Sep 2018
Longer than P75 for phase_2
57 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 16, 2017
CompletedFirst Posted
Study publicly available on registry
June 19, 2017
CompletedStudy Start
First participant enrolled
September 9, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 31, 2023
CompletedResults Posted
Study results publicly available
July 16, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
October 3, 2026
ExpectedApril 13, 2026
January 1, 2026
4.6 years
June 16, 2017
March 7, 2024
April 9, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Objective Response
Response rates will be calculated as the percent of evaluable patients who are responders, and confidence intervals will be constructed accounting for the two-stage design. A responder is defined as a patient who achieves a best response of PR or CR on the study prior to having an overall response of PD; all others will be considered non-responders. The definitions of response are based on a publication (PMID: 25552679) entitled "Criteria for evaluating response and outcome in clinical trials for children with juvenile myelomonocytic leukemia". Patients can be categorized as having experienced complete remission, partial remission, stable disease, or progressive disease based on a combination of clinical and molecular variables.
12 cycles (1 cycle = 28 days)
Secondary Outcomes (6)
Incidence of Adverse Events
Up to cycle 12 (1 cycle = 28 days)
Pharmacokinetic (PK) Parameters of Trametinib
Up to cycle 12 (1 cycle = 28 days)
Trametinib Concentrations
Up to cycle 12 (1 cycle = 28 days)
Mutant Allele Burden
Up to cycle 12 (1 cycle = 28 days)
Complete Response
12 cycles (1 cycle = 28 days)
- +1 more secondary outcomes
Study Arms (1)
Treatment (trametinib)
EXPERIMENTALPatients receive trametinib PO QD on days 1-28 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a bone marrow aspiration or biopsy at baseline, on day 28 of cycles 1 and 2, at all subsequent odd numbered cycles, and at end of treatment.
Interventions
Given PO
Undergo bone marrow aspiration or biopsy
Eligibility Criteria
You may qualify if:
- Patients must be \>= 1 month and \< 22 years of age at the time of study entry
- Patients must have had histologic verification of juvenile myelomonocytic leukemia (JMML) at original diagnosis and currently have relapsed or refractory disease; the diagnosis is made based on the following criteria
- JMML category 1 (all of the following): the diagnostic criteria must include all features in category 1 and EITHER (i) one of the features in category 2 OR (ii) two features from category 3 to make the diagnosis
- Splenomegaly
- \> 1000 (1 x 10\^9/uL) circulating monocytes
- \< 20% blasts in the bone marrow or peripheral blood
- Absence of the t(9;22) or BCR/ABL fusion gene
- JMML category 2 (at least one of the following if at least two category 3 criteria are not present):
- Somatic mutation in RAS or PTPN11
- Clinical diagnosis of NF1 or NF1 gene mutation
- Homozygous mutation in CBL
- Monosomy 7
- JMML category 3 (at least two of the following if no category 2 criteria are met):
- Circulating myeloid precursors
- White blood cell count, \> 10 000 (10 x 10\^9/ uL)
- +35 more criteria
You may not qualify if:
- Patients who are pregnant or breast-feeding are not eligible for this study as there is yet no available information regarding human fetal or teratogenic toxicities; negative pregnancy tests must be obtained in girls who are post-menarchal; patients of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study therapy; women of childbearing potential should be advised to use effective contraception for 4 months after the last dose of trametinib; trametinib may also potentially be secreted in milk and therefore breastfeeding women are excluded; female patients should not breastfeed during treatment with trametinib, and for 4 months following the last dose; male patients must use a condom during intercourse and agree not to father a child during therapy and for 4 months following discontinuation of trametinib to avoid unnecessary exposure of trametinib to the fetus
- Concomitant Medications
- Corticosteroids: patients requiring corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the 7 days prior to enrollment are not eligible; if used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid
- Note: hydrocortisone used as a pre-medication to prevent transfusion related reactions is not considered a concomitant corticosteroid
- Investigational drugs: patients who are currently receiving another investigational drug are not eligible
- Anti-cancer agents: patients who are currently receiving other anti-cancer agents are not eligible (except patients receiving hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy)
- Anti-graft versus host disease (GVHD) or agents to prevent organ rejection post-transplant: patients who are receiving cyclosporine, tacrolimus or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial
- Cardiac medications: any medications for treatment of left ventricular systolic dysfunction
- Patients who have an uncontrolled infection are not eligible
- Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
- Patients with a history of hepatic sinusoid obstructive syndrome (veno-occlusive disease) within the prior 3 months are not eligible
- Patients with a history of or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR) are not eligible
- Patients with a history of RVO or CSR, or predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension
- Patients with uncontrolled systemic disease(s) such as hypertension or diabetes mellitus are not eligible; blood pressure must be =\< the 95th percentile for age, height, and gender
- Patients with a history of allergic reaction attributed to compounds of similar chemical or biologic composition to the MEK inhibitor, trametinib are not eligible
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Children's Oncology Groupcollaborator
- National Cancer Institute (NCI)lead
Study Sites (57)
Children's Hospital of Alabama
Birmingham, Alabama, 35233, United States
Phoenix Childrens Hospital
Phoenix, Arizona, 85016, United States
Arkansas Children's Hospital
Little Rock, Arkansas, 72202-3591, United States
Kaiser Permanente Downey Medical Center
Downey, California, 90242, United States
Loma Linda University Medical Center
Loma Linda, California, 92354, United States
Kaiser Permanente-Oakland
Oakland, California, 94611, United States
Children's Hospital of Orange County
Orange, California, 92868, United States
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, 94304, United States
UCSF Medical Center-Mission Bay
San Francisco, California, 94158, United States
Children's Hospital Colorado
Aurora, Colorado, 80045, United States
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Denver, Colorado, 80218, United States
Connecticut Children's Medical Center
Hartford, Connecticut, 06106, United States
Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803, United States
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, 32207, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
Nicklaus Children's Hospital
Miami, Florida, 33155, United States
Arnold Palmer Hospital for Children
Orlando, Florida, 32806, United States
Nemours Children's Hospital
Orlando, Florida, 32827, United States
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida, 33607, United States
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, 30329, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611, United States
Saint Jude Midwest Affiliate
Peoria, Illinois, 61637, United States
Riley Hospital for Children
Indianapolis, Indiana, 46202, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536, United States
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, 55404, United States
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455, United States
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
The Steven and Alexandra Cohen Children's Medical Center of New York
New Hyde Park, New York, 11040, United States
Mount Sinai Hospital
New York, New York, 10029, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032, United States
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
Nationwide Children's Hospital
Columbus, Ohio, 43205, United States
Dayton Children's Hospital
Dayton, Ohio, 45404, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224, United States
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, 29605, United States
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
The Children's Hospital at TriStar Centennial
Nashville, Tennessee, 37203, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232, United States
Dell Children's Medical Center of Central Texas
Austin, Texas, 78723, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030, United States
Methodist Children's Hospital of South Texas
San Antonio, Texas, 78229, United States
Primary Children's Hospital
Salt Lake City, Utah, 84113, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Related Publications (2)
Stieglitz E, Lee AG, Angus SP, Davis C, Barkauskas DA, Hall D, Kogan SC, Meyer J, Rhodes SD, Tasian SK, Xuei X, Shannon K, Loh ML, Fox E, Weigel BJ. Efficacy of the Allosteric MEK Inhibitor Trametinib in Relapsed and Refractory Juvenile Myelomonocytic Leukemia: a Report from the Children's Oncology Group. Cancer Discov. 2024 Sep 4;14(9):1590-1598. doi: 10.1158/2159-8290.CD-23-1376.
PMID: 38867349DERIVEDMcCullough KB, Kuhn AK, Patnaik MM. Treatment advances for pediatric and adult onset neoplasms with monocytosis. Curr Hematol Malig Rep. 2021 Jun;16(3):256-266. doi: 10.1007/s11899-021-00622-8. Epub 2021 Mar 16.
PMID: 33728588DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Results Reporting Coordinator
- Organization
- Children's Oncology Group
Study Officials
- PRINCIPAL INVESTIGATOR
Elliot Stieglitz
Children's Oncology Group
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 16, 2017
First Posted
June 19, 2017
Study Start
September 9, 2018
Primary Completion
March 31, 2023
Study Completion (Estimated)
October 3, 2026
Last Updated
April 13, 2026
Results First Posted
July 16, 2024
Record last verified: 2026-01