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Juvenile Myelomonocytic LeukemiaPhase 2NCT03190915

Trametinib in Treating Patients With Relapsed or Refractory Juvenile Myelomonocytic Leukemia

A Phase 2 study testing Bone Marrow Aspiration and Biopsy and Trametinib in people with Juvenile Myelomonocytic Leukemia and Neurofibromatosis Type 1, run by National Cancer Institute (NCI) at 57 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 1 month to 21 years
What is being tested?
Bone Marrow Aspiration and Biopsy and Trametinib
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
57 sitesUnited States
Study dates
9 Sep 2018to 14 Oct 2027
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 1 month to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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
Show all 50Show fewer
  • 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)
  • Increased hemoglobin F for age
  • Clonal cytogenetic abnormality
  • GM-CSF hypersensitivity
  • Patients with refractory or relapsed JMML must have had at least one cycle of intensive frontline therapy or at least 2 cycles of a deoxyribonucleic acid (DNA) demethylating agent with persistence of disease, defined by clinical symptoms or the presence of a clonal abnormality; frontline therapy is defined as one cycle of intravenous chemotherapy that includes any of the following agents: fludarabine, cytarabine, or any anthracycline but specifically excludes oral 6-mercaptopurine; frontline therapy will also include any conditioning regimen as part of a stem cell transplant; patients who transform to AML at any point with more than 20% blasts are not eligible for this trial
  • Patients must have a Lansky or Karnofsky performance status score of >= 50, corresponding to Eastern Cooperative Oncology Group (ECOG) categories 0, 1 or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
  • Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to study enrollment
  • Myelosuppressive chemotherapy: patients must have completely recovered from all acute toxic effects of chemotherapy, immunotherapy or radiotherapy prior to study enrollment; at least 14 days must have elapsed since the completion of cytotoxic therapy, with the exception of hydroxyurea
  • Note: cytoreduction with hydroxyurea can be initiated and continued for up to 24 hours prior to the start of protocol therapy
  • Hematopoietic growth factors: at least 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
  • Biologic (anti-neoplastic agent): at least 7 days must have elapsed since completion of therapy with a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period prior to enrollment must be extended beyond the time during which adverse events are known to occur
  • Monoclonal antibodies:
  • At least 30 days after the completion of any type of immunotherapy, e.g. tumor vaccines
  • At least 3 half-lives must have elapsed since prior therapy that included a monoclonal antibody
  • Radiotherapy:
  • >= 2 weeks must have elapsed since local palliative external radiation therapy (XRT) (small port)
  • >= 6 months must have elapsed if prior craniospinal XRT was received, if >= 50% of the pelvis was irradiated, or if traumatic brain injury (TBI) was received
  • >= 4 weeks must have elapsed if other substantial bone marrow irradiation was given
  • Stem cell transplant or rescue without TBI: no evidence of active graft versus (vs.) host disease and >= 3 months must have elapsed since transplant; >= 4 weeks must have elapsed since any donor lymphocyte infusion
  • Patients must not be known to be refractory to red blood cell or platelet transfusions
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 (within 7 days prior to enrollment) or a serum creatinine based on age/gender as follows (within 7 days prior to enrollment):
  • Age: Maximum serum creatinine (mg/dL)
  • 1 month to < 6 months: 0.4 (male) 0.4 (female)
  • 6 months to < 1 year: 0.5 (male) 0.5 (female)
  • 1 to < 2 years: 0.6 (male) 0.6 (female)
  • 2 to < 6 years: 0.8 (male) 0.8 (female)
  • 6 to < 10 years: 1 (male) 1 (female)
  • 10 to < 13 years: 1.2 (male) 1.2 (female)
  • 13 to < 16 years: 1.5 (male) 1.4 (female)
  • >= 16 years: 1.7 (male) 1.4 (female)
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 x ULN (=< 135 U/L) (within 7 days prior to enrollment) (for the purpose of this study, the ULN for SGPT is 45 U/L)
  • Serum albumin >= 2 g/dL (within 7 days prior to enrollment)
  • Shortening fraction of >= 27% by echocardiogram OR ejection fraction of >= 50% by multi-gated acquisition (MUGA)
  • Corrected QT (by Bazett's formula [QTcB]) interval < 450 msecs
  • Patients must be able to swallow tablets or liquid; use of a nasogastric or gastrostomy (G) tube is also allowed

Who cannot join

  • 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)
Show all 16Show fewer
  • 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
  • Patients with a clinical diagnosis of Noonan syndrome are not eligible; Note: patients with Casitas B-lineage lymphoma (CBL) syndrome, also known as Noonan-like syndrome, are eligible to enroll

Trial locations and contacts

57 sites in 1 country.

57 sites in 1 country

United States57 sites

  • C S Mott Children's Hospital

    Ann Arbor, Michigan, 48109

  • Children's Healthcare of Atlanta - Arthur M Blank Hospital

    Atlanta, Georgia, 30329

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • Dell Children's Medical Center of Central Texas

    Austin, Texas, 78723

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

  • Children's Hospital of Alabama

    Birmingham, Alabama, 35233

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Carolinas Medical Center/Levine Cancer Institute

    Charlotte, North Carolina, 28203

  • Lurie Children's Hospital-Chicago

    Chicago, Illinois, 60611

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

  • Dayton Children's Hospital

    Dayton, Ohio, 45404

  • Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center

    Denver, Colorado, 80218

  • Kaiser Permanente Downey Medical Center

    Downey, California, 90242

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • BI-LO Charities Children's Cancer Center

    Greenville, South Carolina, 29605

  • Connecticut Children's Medical Center

    Hartford, Connecticut, 06106

  • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

    Houston, Texas, 77030

  • Riley Hospital for Children

    Indianapolis, Indiana, 46202

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • Nemours Children's Clinic-Jacksonville

    Jacksonville, Florida, 32207

  • Children's Mercy Hospitals and Clinics

    Kansas City, Missouri, 64108

  • University of Kentucky/Markey Cancer Center

    Lexington, Kentucky, 40536

  • Arkansas Children's Hospital

    Little Rock, Arkansas, 72202-3591

  • Loma Linda University Medical Center

    Loma Linda, California, 92354

  • Saint Jude Children's Research Hospital

    Memphis, Tennessee, 38105

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, 33136

  • Nicklaus Children's Hospital

    Miami, Florida, 33155

  • Children's Hospital of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Children's Hospitals and Clinics of Minnesota - Minneapolis

    Minneapolis, Minnesota, 55404

  • University of Minnesota/Masonic Cancer Center

    Minneapolis, Minnesota, 55455

  • The Children's Hospital at TriStar Centennial

    Nashville, Tennessee, 37203

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • The Steven and Alexandra Cohen Children's Medical Center of New York

    New Hyde Park, New York, 11040

  • Mount Sinai Hospital

    New York, New York, 10029

  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

  • Kaiser Permanente-Oakland

    Oakland, California, 94611

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Children's Hospital of Orange County

    Orange, California, 92868

  • Arnold Palmer Hospital for Children

    Orlando, Florida, 32806

  • Nemours Children's Hospital

    Orlando, Florida, 32827

  • Lucile Packard Children's Hospital Stanford University

    Palo Alto, California, 94304

  • OSF Children's Hospital of Illinois

    Peoria, Illinois, 61637

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Phoenix Childrens Hospital

    Phoenix, Arizona, 85016

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15224

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Primary Children's Hospital

    Salt Lake City, Utah, 84113

  • Methodist Children's Hospital of South Texas

    San Antonio, Texas, 78229

  • UCSF Medical Center-Mission Bay

    San Francisco, California, 94158

  • Seattle Children's Hospital

    Seattle, Washington, 98105

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Saint Joseph's Hospital/Children's Hospital-Tampa

    Tampa, Florida, 33607

  • MedStar Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

  • Alfred I duPont Hospital for Children

    Wilmington, Delaware, 19803

Other trials in United States

About this study

Official title: A Phase 2 Study of the MEK Inhibitor Trametinib (NSC# 763093) in Children With Relapsed or Refractory Juvenile Myelomonocytic Leukemia

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine the objective response rate to trametinib in children with recurrent or refractory juvenile myelomonocytic leukemia (JMML).

SECONDARY OBJECTIVES:

  1. To further define and describe the toxicities of single agent trametinib in children with recurrent or refractory JMML.

II. To further characterize the pharmacokinetics of trametinib in children with recurrent or refractory JMML.

III. To prospectively evaluate mutant allele burden as a marker of disease activity in JMML.

IV. To measure the rate of complete responses in children with recurrent or refractory JMML.

  1. To measure the duration of response among responders.

EXPLORATORY OBJECTIVE:

  1. To describe the distribution of JMML diagnostic criteria in children with recurrent or refractory JMML.

OUTLINE:

Patients receive trametinib orally (PO) once daily (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.

After completion of study treatment, patients are followed up annually for up to 5 years.

Being tested
Bone Marrow Aspiration and Biopsy, Trametinib
Medical subject headings
Leukemia, Myelomonocytic, Juvenile, Neurofibromatosis 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Bone Marrow Aspiration and BiopsyProcedure or surgery

    Undergo bone marrow aspiration or biopsy

  • TrametinibDrug

    Also called GSK 1120212, GSK 212, GSK-1120212, GSK-212

    Given PO

Study groups in NCT03190915
Study groupRoleWhat they receive
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.
Receives: Procedure: Bone Marrow Aspiration and Biopsy; Drug: Trametinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 12 cycles (1 cycle = 28 days)

Secondary outcomes (6)

  1. Incidence of Adverse Events

    Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Will report the percentage of patients within each disease stratum who experienced a grade 3 or higher toxicity with attribution of possible, probable, or definite while on protocol therapy or within 30 days of the last dose of therapy.

    Measured: Up to cycle 12 (1 cycle = 28 days)

  2. Pharmacokinetic (PK) Parameters of Trametinib

    A descriptive analysis of pharmacokinetic parameters of trametinib will be performed to define systemic exposure, drug clearance, Trametinib concentrations, and other pharmacokinetic parameters. The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).

    Measured: Up to cycle 12 (1 cycle = 28 days)

  3. Trametinib Concentrations

    Will be measured by mass spectrometry. Will be analyzed descriptively. Values will be summarized with means and standard deviations.

    Measured: Up to cycle 12 (1 cycle = 28 days)

  4. Mutant Allele Burden

    Will be measured by next-generation sequencing. The percent change in mutant allele burden will be analyzed descriptively. Values will be summarized with means and standard deviations.

    Measured: Up to cycle 12 (1 cycle = 28 days)

  5. Complete Response

    Complete Response rates will be calculated as the percent of evaluable patients who had an overall best response of Complete Response, and confidence intervals will be constructed accounting for the two-stage design.

    Measured: 12 cycles (1 cycle = 28 days)

  6. Duration of Response

    Duration of response (Aim 1.2.5) will be defined as the time from first occurrence of PR or CR until the first occurrence of PD, death, or going off study. Patients who progress will be considered to have had an event, patients who die prior to progressing will be considered to have a competing event, and patients who go off study prior to progressing will be censored at time of last contact. The analysis will be done using the method of Gray.

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Jun 2017
  2. Study start9 Sep 2018
  3. Primary completion31 Mar 2023
  4. Study completion14 Oct 2027 (estimated)

Resources

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
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03190915
Sponsor's protocol ID
NCI-2017-00921
Other IDs
NCI-2017-00921, ADVL1521, ADVL1521, U10CA180886, U54CA196519
Status last verified
Jul 2026
First submitted
16 Jun 2017
Last updated
3 Nov 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 38867349

  • McCullough 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.

    PubMed 33728588

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bone Marrow Aspiration and Biopsy and Trametinib in people with Juvenile Myelomonocytic Leukemia and Neurofibromatosis Type 1, run by National Cancer Institute (NCI) at 57 sites 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 50 inclusion and 16 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: under way, not looking for participants, as of the sponsor's last update on 3 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 57 sites 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 16 Jul 2024). 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?

Objective Response (time frame: 12 cycles (1 cycle = 28 days)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03190915, which also lists 2 linked publications.

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 Nov 2026.

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