Trial Outcomes & Findings for Trametinib in Treating Patients With Relapsed or Refractory Juvenile Myelomonocytic Leukemia (NCT NCT03190915)

NCT ID: NCT03190915

Last Updated: 2025-10-29

Results Overview

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.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

10 participants

Primary outcome timeframe

12 cycles (1 cycle = 28 days)

Results posted on

2025-10-29

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment (Trametinib) 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.
Overall Study STARTED	10
Overall Study COMPLETED	3
Overall Study NOT COMPLETED	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment (Trametinib) 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.
Overall Study Physician Determines It Is In Patient's Best Interest	4
Overall Study Progressive Disease	3

Baseline Characteristics

Trametinib in Treating Patients With Relapsed or Refractory Juvenile Myelomonocytic Leukemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Trametinib) n=10 Participants 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.
Age, Categorical <=18 years	10 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	1.96 years n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12 cycles (1 cycle = 28 days)

Population: All patients who met the evaluable for response criteria outlined in section 9.4 of the ADVL1521 protocol.

Outcome measures

Outcome measures
Measure	Treatment (Trametinib) n=10 Participants 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.
Objective Response	50.0 Percentage of patients Interval 18.7 to 81.3

SECONDARY outcome

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

Population: All patients who met the evaluable for response criteria outlined in section 9.4 of the ADVL1521 protocol.

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.

Outcome measures

Outcome measures
Measure	Treatment (Trametinib) n=10 Participants 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.
Incidence of Adverse Events	30.0 Percentage of patients Interval 6.7 to 65.2

SECONDARY outcome

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

Population: Pharmacokinetic samples were collected and run, and the assay results were reviewed. However, two experts who reviewed the data found it to be uninterpretable because it was generated using incorrect standard curves.

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).

Outcome measures

Outcome data not reported

SECONDARY outcome

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

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

Outcome measures

Outcome data not reported

SECONDARY outcome

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

Population: All patients who met the evaluable for response criteria outlined in section 9.4 of the ADVL1521 protocol.

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.

Outcome measures

Outcome measures
Measure	Treatment (Trametinib) n=10 Participants 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.
Mutant Allele Burden	0.0 Percent Change In Mutant Allele Burden Standard Deviation 0

SECONDARY outcome

Timeframe: 12 cycles (1 cycle = 28 days)

Population: All patients who met the evaluable for response criteria outlined in section 9.4 of the ADVL1521 protocol.

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.

Outcome measures

Outcome measures
Measure	Treatment (Trametinib) n=10 Participants 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.
Complete Response	0.0 Percentage of patients Interval 0.0 to 30.8

SECONDARY outcome

Timeframe: Up to 5 years

Population: All patients who achieved an overall best response of Partial Response or Complete 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.

Outcome measures

Outcome measures
Measure	Treatment (Trametinib) n=5 Participants 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.
Duration of Response	2.26 years Interval 0.87 to 2.78

Adverse Events

Treatment (Trametinib)

Serious events: 4 serious events

Other events: 8 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Trametinib) n=10 participants at risk 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.
Gastrointestinal disorders Diarrhea	10.0% 1/10 • Adverse Events monitored/assessed up to 30 days after treatment (12 cycles). All-Cause Mortality monitored/assessed up to 5 years from study enrollment. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.
Skin and subcutaneous tissue disorders Rash maculo-papular	10.0% 1/10 • Adverse Events monitored/assessed up to 30 days after treatment (12 cycles). All-Cause Mortality monitored/assessed up to 5 years from study enrollment. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.
Respiratory, thoracic and mediastinal disorders Respiratory failure	20.0% 2/10 • Adverse Events monitored/assessed up to 30 days after treatment (12 cycles). All-Cause Mortality monitored/assessed up to 5 years from study enrollment. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.
Infections and infestations Sepsis	20.0% 2/10 • Adverse Events monitored/assessed up to 30 days after treatment (12 cycles). All-Cause Mortality monitored/assessed up to 5 years from study enrollment. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.
Respiratory, thoracic and mediastinal disorders Stridor	10.0% 1/10 • Adverse Events monitored/assessed up to 30 days after treatment (12 cycles). All-Cause Mortality monitored/assessed up to 5 years from study enrollment. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.
Infections and infestations Upper respiratory infection	10.0% 1/10 • Adverse Events monitored/assessed up to 30 days after treatment (12 cycles). All-Cause Mortality monitored/assessed up to 5 years from study enrollment. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.

Other adverse events

Other adverse events
Measure	Treatment (Trametinib) n=10 participants at risk 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.
Blood and lymphatic system disorders Anemia	10.0% 1/10 • Adverse Events monitored/assessed up to 30 days after treatment (12 cycles). All-Cause Mortality monitored/assessed up to 5 years from study enrollment. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.
Gastrointestinal disorders Diarrhea	20.0% 2/10 • Adverse Events monitored/assessed up to 30 days after treatment (12 cycles). All-Cause Mortality monitored/assessed up to 5 years from study enrollment. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.
Skin and subcutaneous tissue disorders Dry skin	10.0% 1/10 • Adverse Events monitored/assessed up to 30 days after treatment (12 cycles). All-Cause Mortality monitored/assessed up to 5 years from study enrollment. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.
General disorders Fever	20.0% 2/10 • Adverse Events monitored/assessed up to 30 days after treatment (12 cycles). All-Cause Mortality monitored/assessed up to 5 years from study enrollment. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.
Infections and infestations Folliculitis	10.0% 1/10 • Adverse Events monitored/assessed up to 30 days after treatment (12 cycles). All-Cause Mortality monitored/assessed up to 5 years from study enrollment. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.
Vascular disorders Hypertension	10.0% 1/10 • Adverse Events monitored/assessed up to 30 days after treatment (12 cycles). All-Cause Mortality monitored/assessed up to 5 years from study enrollment. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.
Vascular disorders Hypotension	10.0% 1/10 • Adverse Events monitored/assessed up to 30 days after treatment (12 cycles). All-Cause Mortality monitored/assessed up to 5 years from study enrollment. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.
Investigations Neutrophil count decreased	20.0% 2/10 • Adverse Events monitored/assessed up to 30 days after treatment (12 cycles). All-Cause Mortality monitored/assessed up to 5 years from study enrollment. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.
Infections and infestations Paronychia	20.0% 2/10 • Adverse Events monitored/assessed up to 30 days after treatment (12 cycles). All-Cause Mortality monitored/assessed up to 5 years from study enrollment. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.
Investigations Platelet count decreased	30.0% 3/10 • Adverse Events monitored/assessed up to 30 days after treatment (12 cycles). All-Cause Mortality monitored/assessed up to 5 years from study enrollment. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.
Skin and subcutaneous tissue disorders Rash maculo-papular	30.0% 3/10 • Adverse Events monitored/assessed up to 30 days after treatment (12 cycles). All-Cause Mortality monitored/assessed up to 5 years from study enrollment. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.
Cardiac disorders Sinus tachycardia	10.0% 1/10 • Adverse Events monitored/assessed up to 30 days after treatment (12 cycles). All-Cause Mortality monitored/assessed up to 5 years from study enrollment. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	30.0% 3/10 • Adverse Events monitored/assessed up to 30 days after treatment (12 cycles). All-Cause Mortality monitored/assessed up to 5 years from study enrollment. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.
Skin and subcutaneous tissue disorders Urticaria	10.0% 1/10 • Adverse Events monitored/assessed up to 30 days after treatment (12 cycles). All-Cause Mortality monitored/assessed up to 5 years from study enrollment. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.
Respiratory, thoracic and mediastinal disorders Laryngeal obstruction	10.0% 1/10 • Adverse Events monitored/assessed up to 30 days after treatment (12 cycles). All-Cause Mortality monitored/assessed up to 5 years from study enrollment. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.
Infections and infestations Soft tissue infection	10.0% 1/10 • Adverse Events monitored/assessed up to 30 days after treatment (12 cycles). All-Cause Mortality monitored/assessed up to 5 years from study enrollment. Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.

Additional Information

Results Reporting Coordinator

Children's Oncology Group

Phone: 16264470064

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60