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Trametinib in Treating Patients With Relapsed or Refractory Juvenile Myelomonocytic Leukemia

Primary Purpose

Juvenile Myelomonocytic Leukemia, Neurofibromatosis Type 1

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Bone Marrow Aspiration and Biopsy
Trametinib
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Juvenile Myelomonocytic Leukemia

Eligibility Criteria

1 Month - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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)
      • 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

Exclusion Criteria:

  • 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
  • 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

Sites / Locations

  • Children's Hospital of Alabama
  • Phoenix Childrens Hospital
  • Arkansas Children's Hospital
  • Kaiser Permanente Downey Medical Center
  • Loma Linda University Medical Center
  • Kaiser Permanente-Oakland
  • Children's Hospital of Orange County
  • Lucile Packard Children's Hospital Stanford University
  • UCSF Medical Center-Mission Bay
  • Children's Hospital Colorado
  • Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
  • Connecticut Children's Medical Center
  • Alfred I duPont Hospital for Children
  • MedStar Georgetown University Hospital
  • Children's National Medical Center
  • Nemours Children's Clinic-Jacksonville
  • University of Miami Miller School of Medicine-Sylvester Cancer Center
  • Nicklaus Children's Hospital
  • Arnold Palmer Hospital for Children
  • Nemours Children's Hospital
  • Saint Joseph's Hospital/Children's Hospital-Tampa
  • Children's Healthcare of Atlanta - Egleston
  • Lurie Children's Hospital-Chicago
  • Saint Jude Midwest Affiliate
  • Riley Hospital for Children
  • University of Iowa/Holden Comprehensive Cancer Center
  • University of Kentucky/Markey Cancer Center
  • National Institutes of Health Clinical Center
  • Dana-Farber Cancer Institute
  • C S Mott Children's Hospital
  • Children's Hospitals and Clinics of Minnesota - Minneapolis
  • University of Minnesota/Masonic Cancer Center
  • Children's Mercy Hospitals and Clinics
  • Washington University School of Medicine
  • The Steven and Alexandra Cohen Children's Medical Center of New York
  • Mount Sinai Hospital
  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
  • Carolinas Medical Center/Levine Cancer Institute
  • Duke University Medical Center
  • Cincinnati Children's Hospital Medical Center
  • Nationwide Children's Hospital
  • Dayton Children's Hospital
  • University of Oklahoma Health Sciences Center
  • Oregon Health and Science University
  • Children's Hospital of Philadelphia
  • Children's Hospital of Pittsburgh of UPMC
  • BI-LO Charities Children's Cancer Center
  • Saint Jude Children's Research Hospital
  • The Children's Hospital at TriStar Centennial
  • Vanderbilt University/Ingram Cancer Center
  • Dell Children's Medical Center of Central Texas
  • UT Southwestern/Simmons Cancer Center-Dallas
  • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
  • Methodist Children's Hospital of South Texas
  • Primary Children's Hospital
  • Seattle Children's Hospital
  • Children's Hospital of Wisconsin

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (trametinib)

Arm Description

Patients 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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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).
Trametinib concentrations
Will be measured by mass spectrometry. Will be analyzed descriptively. Values will be summarized with means and standard deviations.
Mutant allele burden
Will be measured by next-generation sequencing. Will be analyzed descriptively. Values will be summarized with means and standard deviations.
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.
Duration of Response
The 2-year Event-Free Survival will be estimated using Kaplan-Meier methodology.

Full Information

First Posted
June 16, 2017
Last Updated
October 7, 2023
Sponsor
National Cancer Institute (NCI)
Collaborators
Children's Oncology Group
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1. Study Identification

Unique Protocol Identification Number
NCT03190915
Brief Title
Trametinib in Treating Patients With Relapsed or Refractory Juvenile Myelomonocytic Leukemia
Official Title
A Phase 2 Study of the MEK Inhibitor Trametinib (NSC# 763093) in Children With Relapsed or Refractory Juvenile Myelomonocytic Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 9, 2018 (Actual)
Primary Completion Date
March 31, 2023 (Actual)
Study Completion Date
September 22, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)
Collaborators
Children's Oncology Group

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
Detailed Description
PRIMARY OBJECTIVE: I. To determine the objective response rate to trametinib in children with recurrent or refractory juvenile myelomonocytic leukemia (JMML). SECONDARY OBJECTIVES: I. 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. V. To measure the duration of response among responders. EXPLORATORY OBJECTIVE: I. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Juvenile Myelomonocytic Leukemia, Neurofibromatosis Type 1

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (trametinib)
Arm Type
Experimental
Arm Description
Patients 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.
Intervention Type
Procedure
Intervention Name(s)
Bone Marrow Aspiration and Biopsy
Intervention Description
Undergo bone marrow aspiration or biopsy
Intervention Type
Drug
Intervention Name(s)
Trametinib
Other Intervention Name(s)
GSK 1120212, GSK-1120212, GSK1120212, JTP-74057, MEK Inhibitor GSK1120212
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Objective response
Description
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.
Time Frame
12 cycles (1 cycle = 28 days)
Secondary Outcome Measure Information:
Title
Incidence of adverse events
Description
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.
Time Frame
Up to cycle 12 (1 cycle = 28 days)
Title
Pharmacokinetic (PK) parameters of trametinib
Description
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).
Time Frame
Up to cycle 12 (1 cycle = 28 days)
Title
Trametinib concentrations
Description
Will be measured by mass spectrometry. Will be analyzed descriptively. Values will be summarized with means and standard deviations.
Time Frame
Up to cycle 12 (1 cycle = 28 days)
Title
Mutant allele burden
Description
Will be measured by next-generation sequencing. Will be analyzed descriptively. Values will be summarized with means and standard deviations.
Time Frame
Up to cycle 12 (1 cycle = 28 days)
Title
Complete Response
Description
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.
Time Frame
12 cycles (1 cycle = 28 days)
Title
Duration of Response
Description
The 2-year Event-Free Survival will be estimated using Kaplan-Meier methodology.
Time Frame
2-year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Month
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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) 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 Exclusion Criteria: 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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Elliot Stieglitz
Organizational Affiliation
Children's Oncology Group
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hospital of Alabama
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Phoenix Childrens Hospital
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85016
Country
United States
Facility Name
Arkansas Children's Hospital
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72202-3591
Country
United States
Facility Name
Kaiser Permanente Downey Medical Center
City
Downey
State/Province
California
ZIP/Postal Code
90242
Country
United States
Facility Name
Loma Linda University Medical Center
City
Loma Linda
State/Province
California
ZIP/Postal Code
92354
Country
United States
Facility Name
Kaiser Permanente-Oakland
City
Oakland
State/Province
California
ZIP/Postal Code
94611
Country
United States
Facility Name
Children's Hospital of Orange County
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Lucile Packard Children's Hospital Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
UCSF Medical Center-Mission Bay
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Connecticut Children's Medical Center
City
Hartford
State/Province
Connecticut
ZIP/Postal Code
06106
Country
United States
Facility Name
Alfred I duPont Hospital for Children
City
Wilmington
State/Province
Delaware
ZIP/Postal Code
19803
Country
United States
Facility Name
MedStar Georgetown University Hospital
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Nemours Children's Clinic-Jacksonville
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32207
Country
United States
Facility Name
University of Miami Miller School of Medicine-Sylvester Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Nicklaus Children's Hospital
City
Miami
State/Province
Florida
ZIP/Postal Code
33155
Country
United States
Facility Name
Arnold Palmer Hospital for Children
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Nemours Children's Hospital
City
Orlando
State/Province
Florida
ZIP/Postal Code
32827
Country
United States
Facility Name
Saint Joseph's Hospital/Children's Hospital-Tampa
City
Tampa
State/Province
Florida
ZIP/Postal Code
33607
Country
United States
Facility Name
Children's Healthcare of Atlanta - Egleston
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Lurie Children's Hospital-Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Saint Jude Midwest Affiliate
City
Peoria
State/Province
Illinois
ZIP/Postal Code
61637
Country
United States
Facility Name
Riley Hospital for Children
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
University of Iowa/Holden Comprehensive Cancer Center
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
University of Kentucky/Markey Cancer Center
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
Facility Name
National Institutes of Health Clinical Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
C S Mott Children's Hospital
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Children's Hospitals and Clinics of Minnesota - Minneapolis
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55404
Country
United States
Facility Name
University of Minnesota/Masonic Cancer Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Children's Mercy Hospitals and Clinics
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
The Steven and Alexandra Cohen Children's Medical Center of New York
City
New Hyde Park
State/Province
New York
ZIP/Postal Code
11040
Country
United States
Facility Name
Mount Sinai Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Carolinas Medical Center/Levine Cancer Institute
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28203
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
Dayton Children's Hospital
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45404
Country
United States
Facility Name
University of Oklahoma Health Sciences Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Children's Hospital of Pittsburgh of UPMC
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Facility Name
BI-LO Charities Children's Cancer Center
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Facility Name
Saint Jude Children's Research Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States
Facility Name
The Children's Hospital at TriStar Centennial
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Vanderbilt University/Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Dell Children's Medical Center of Central Texas
City
Austin
State/Province
Texas
ZIP/Postal Code
78723
Country
United States
Facility Name
UT Southwestern/Simmons Cancer Center-Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Methodist Children's Hospital of South Texas
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Primary Children's Hospital
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84113
Country
United States
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Name
Children's Hospital of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
33728588
Citation
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.
Results Reference
derived

Learn more about this trial

Trametinib in Treating Patients With Relapsed or Refractory Juvenile Myelomonocytic Leukemia

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