Health TrialsbyHealthPanel

A Phase I/II Study of Trametinib and Azacitidine for Patients With Newly Diagnosed Juvenile Myelomonocytic Leukemia

ConditionsLeukemia, Juvenile MyelomonocyticJMMLJCMLNeurofibromatosis 1CBL Syndrome
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age1-21
SponsorTherapeutic Advances in Childhood Leukemia Consortium

About this trial

This clinical trial will test the safety and efficacy of combining trametinib and azacitidine in patients with juvenile myelomonocytic leukemia (JMML). Newly diagnosed lower-risk JMML patients will receive trametinib and azacitidine. High-risk JMML patients will receive trametinib, azacitidine, fludarabine, and cytarabine.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Peripheral blood monocyte count ≥ 1 × 109/L*

Splenomegaly†

Blast percentage in PB and BM < 20%

Absence of BCR::ABL1

Disqualifiers

Patients cannot have a known allergy to any of the drugs used in the study.

Patients cannot have a systemic fungal, bacterial, viral, or other infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment. The patient needs to be off pressors and have negative blood cultures for 48 hours.

Patients cannot have a plan to administer non-protocol chemotherapy, radiation therapy, or immunotherapy during the study period.

Patients cannot have significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance with the protocol treatment or procedures, interfere with consent, study participation, follow up, or interpretation of study results.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Trametinib

    Drug

    PO or NG QD Days 1-28 For patients age \< 6 years: 0.032 mg/kg/day at max dose = 2mg/day For patients age ≥ 6 years: 0.025 mg/kg/day at max dose = 2 mg/day

  • Azacitidine

    Drug

    IV over 30 minutes Days 1-5 Age \< 1 year or weight \<10kg: 2.5 mg/kg/day Age ≥ 1 year and weight ≥ 10kg: 75 mg/m2/day

  • Fludarabine

    Drug

    IV over 30 minutes Days 6-10 30 mg/m2/day (1mg/kg if \<12 kg)

  • Cytarabine

    Drug

    IV over 3 hours Days 6-10 2000 mg/m2/day (67mg/kg if \<12 kg)

Treatment groups

58 Participants
are divided into 2 treatment groups
Group A: Lower-risk patientsExperimental treatment 2 interventions
Group B: High-risk patientsExperimental treatment 4 interventions

Trial outcomes

Primary outcomes

1

To determine the safety of combining trametinib with azacitidine for patients with newly diagnosed lower-risk JMML.

The incidence of dose limiting toxicities (DLTs) after the 1st course of therapy will be measured at different dose levels.

Time frame
At the end of the evaluation period of Cycle 1 (defined as 28 day cycle of therapy plus 30 days following the last dose of study therapy)
2

To determine the safety of combining trametinib with azacitidine (Aza), fludarabine (FLA) and cytarabine for patients with newly diagnosed high-risk JMML.

The incidence of dose limiting toxicities (DLTs) after the 1st course of therapy will be measured at different dose levels.

Time frame
At the end of the evaluation period of Cycle 1 (defined as 28 day cycle of therapy plus 30 days following the last dose of study therapy)

Secondary outcomes

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Therapeutic Advances in Childhood Leukemia Consortium

Lead sponsor

Source ClinicalTrials.gov
Apply now