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PLX3397 in Children and Young Adults With Refractory Leukemias and Refractory Solid Tumors Including Neurofibromatosis Type 1 (NF1) Associated Plexiform Neurofibromas (PN)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02390752
Recruitment Status : Recruiting
First Posted : March 18, 2015
Last Update Posted : July 18, 2022
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:


- Some people with cancer have solid tumors. Others have refractory leukemia. This doesn t go away after treatment. Researchers want to see if a drug called PLX3397 can shrink tumors or stop them from growing.


- To find the highest safe dose and side effects of PLX3397. To see if it helps treat certain types of cancer.


  • People ages 3 22 with a solid tumor or leukemia that has returned or not responded to cancer therapies.
  • For Phase II, people ages 3 31 with a Neurofibromatosis Type 1 (NF1) Associated Plexiform Neurofibroma (PN) that cannot be removed with surgery.


  • Participants will be screened with:
  • Medical history
  • Physical exam
  • Blood and urine tests
  • Heart tests
  • Scans or other tests of the tumor
  • Participants will take PLX3397 as a capsule once daily for a 28-day cycle. They can do this for up to 2 years.
  • During the study, participants will have many tests and procedures. They include repeats of the screening tests. Participants will keep a diary of symptoms.
  • Participants with solid tumors will have scans or x-rays.
  • Participants with NF1 PN will have MRI scans.
  • Participants with leukemia will have blood tests. They may have a bone marrow sample taken.
  • Some participants may have a biopsy.
  • When finished taking PLX3397, participants will have follow-up visits. They will repeat the screening tests and note side effects.
  • Phase II will follow the same procedures as Phase I above, but participants will also fill out questionnaires about their pain and quality of life.

Condition or disease Intervention/treatment Phase
Neurofibroma, Plexiform Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Promyelocytic, Acute Sarcoma Drug: Turalio Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 81 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Trial of PLX3397 in Children and Young Adults With Refractory Leukemias and Refractory Solid Tumors Including Neurofibromatosis Type 1 (NF1) Associated Plexiform Neurofibromas (PN)
Actual Study Start Date : April 29, 2015
Estimated Primary Completion Date : December 1, 2024
Estimated Study Completion Date : December 1, 2024

Arm Intervention/treatment
Experimental: Phase I
take oral drug daily for a 28 day cycle
Drug: Turalio
take oral drug daily for a 28 day cycle

Experimental: Phase II
take oral drug daily for a 28 day cycle
Drug: Turalio
take oral drug daily for a 28 day cycle

Primary Outcome Measures :
  1. Phase II: determine antitumor activity of PLX3397 in patients with NF1 PN [ Time Frame: at each response evaluation ]
    Objective response rate (ORR) will be defined as the proportion of patients with partial response (PR = PN volume decrease >=20% determined by volumetric MRI analysis).

  2. Phase I: determine a phase II dose of PLX3397 [ Time Frame: first cycle ]
    Evaluate the safety and tolerability of Turalio

Secondary Outcome Measures :
  1. Tolerability [ Time Frame: each cycle ]
    Evaluate biologic activity and extended tolerability of PLX3397

  2. To characterize the pharmacokinetic profile [ Time Frame: Cycle 1 and 2 ]
    Preliminarily determine the antitumor activity within the confines of a phase 1 study for recurrent or refractory pediatric solid tumors and leukemia (AML and ALL)

  3. Safety [ Time Frame: prior to cycles 3,5,9, 13 and every 6 cycles ]
    Evaluate patient reported and functional outcomes

  4. Correlative analysis of immune endpoints with response [ Time Frame: before C1 and then C1D7 and then at each restaging evaluation ]
    Determine effect of PLX 3397 on circulating biomarkers

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   3 Years to 35 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
  • Diagnosis:

    • Phase I: Patients must have recurrent or refractory solid tumors or acute leukemia (limited to AML or ALL) or have been intolerant of prior therapies, confirmed by the Laboratory of Pathology, NCI, e.g., solid tumors including rhabdomyosarcoma, Ewing sarcoma, soft tissue sarcomas. These may include primary neoplasms of the central nervous system, such as high-grade (WHO grade III-IV) glioma. Patients with diffuse intrinsic pontine glioma (DIPG) or optic pathway glioma are exempt from histologic verification. For DIPG typical MRI findings must be present which include hypo- or isointense on T1-weighted imaging, hyperintense on FLAIR or T2-weighted imaging, epicenter in the pons in the face of a typical clinical presentation. Optic pathway glioma are located in the optic pathway and are typically hypo- or iso-intense on T1 and hyperintense on T2-weighted images.
    • In addition, patients with NF1 and with malignant peripheral nerve sheath tumor (MPNST).
    • Phase II: inoperable PN causing morbidity, such as (but not limited to) head and neck lesions that could compromise the airway or great vessels, brachial or lumbar plexus lesions that could cause nerve compression and loss of function, lesions that could result in major deformity (e.g., orbital lesions) or significant cosmetic problems, lesions of the extremity that cause limb hypertrophy or loss of function, and painful lesions in patients with NF1.
    • Histologic confirmation of PN tumor is not necessary in the presence of consistent clinical and radiographic findings but should be considered if malignant degeneration of a PN is clinically suspected.
    • A PN is defined as a neurofibroma that has grown along the length of a nerve and may involve multiple fascicles and branches. A spinal PN involves two or more levels with connection between the levels or extending laterally along the nerve. In addition to PN, all study subjects must have either positive genetic testing for NF1 confirmed in a CLIA certified laboratory or have at least one other diagnostic criterion for NF1 listed below (NIH Consensus conference):

      • Six or more cafe-au-lait macules (greater than or equal to 0.5cm in prepubertal subjects or greater than or equal to 1.5 cm in post pubertal subjects)
      • Freckling in axilla or groin
      • Optic glioma
      • Two or more Lisch nodules
      • A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)
      • A first-degree relative with NF1
      • Patients must have relapsed after or be refractory to effective standard therapies. For NF1 PN there is no standard medical therapy, and therefore no requirement for prior therapy. There are no limits on number of prior therapeutic regimens.
  • Disease status: Phase I: Patients with refractory solid tumors including patients with NF1 and MPNST must have evaluable disease, patients with leukemia must have measurable or evaluable disease at the time of enrollment, which may include any evidence of disease including minimal residual disease detected by flow cytometry.

    --Phase II: Patients must have measurable disease.

  • Age (must have BSA greater than or equal to 0.55 m^2):

    • Phase I: greater than or equal to 3 and less than or equal to 21 years of age
    • Phase II: greater than or equal to 3 and less than or equal to 35 years of age
  • Ability of subject or Legally Authorized Representative [LAR] (the parent/guardian if subject is a minor) to understand and the willingness to sign a written informed consent document.
  • Patients must be able to swallow capsules.
  • Performance Status: Karnofsky greater than or equal to 50% for patients > 16 years of age and Lansky greater than or equal to 50% for patients less than or eqal to 16 years of age. Subjects who are wheelchair bound because of paralysis will be considered "ambulatory" when they are up in their wheelchair. Subjects have to be able to travel to the NIH for evaluations.
  • Prior therapy:

Patients must have fully recovered (to Grade 1) from the acute toxic effects of all prior anti-cancer therapy.

  • Myelosuppressive chemotherapy: At least 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea).
  • Biologic (anti-neoplastic agent): At least 7 days after the last dose of a biologic agent. 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. The duration of this interval must be discussed with the study chair.
  • Immunotherapy: At least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines.
  • Monoclonal antibodies: At least 3 half-lives of the antibody after the last dose of a monoclonal antibody.
  • XRT: At least 7 days after local palliative XRT (small port); At least 150 days must have elapsed if prior TBI or if greater than or equal to 50% radiation of pelvis; greater than or equal to 14 days from whole brain radiation, craniospinal radiation, or targeted radiation to CNS tumors. At least 42 days must have elapsed if other substantial BM radiation.
  • HSCT: greater than or equal to 56 days from stem cell transplant with no evidence of active graft vs. host disease; must be off immunosuppressive therapy for at least 4 weeks and have no active graft-versus-host disease (GVHD) at the time of entry onto this trial.
  • Surgery: greater than or equal to 14 days from surgery
  • Others: greater than or equal to 7 days from last dose of short active hematopoietic growth factors, i.e. filgrastim, greater than or equal to 14 days for long-acting, i.e. pegfilgrastim.
  • Steroids: Patients with CNS tumors who are managed with steroids are eligible if they have no worsening neurologic deficits and are on a stable or decreasing dose of corticosteroids for greater than or equal to 7 days prior to registration. Patients with leukemia receiving corticosteroids or hydroxyurea are eligible provided that the corticosteroids are not being used to manage GVHD and there has been no increase in corticosteroid of hydroxyurea dose for 7 days prior to starting PLX3397

    - Patient must have adequate hematologic, hepatic, and renal function, defined by:

  • Absolute neutrophil count >= 1.5 (SqrRoot) 10^9/L
  • Hemoglobin > 10 g/dL
  • Platelet count >= 100 (SqrRoot) 10^9/L
  • AST and ALT less than or equal to upper limit of normal (ULN)
  • TBil and DBil less than or equal to ULN with an exception of patients with confirmed Gilbert's syndrome. For

patients with confirmed Gilberts syndrome, the TBil should be less than or equal to 1.5 (SqrRoot) ULN

  • Serum creatinine less than or equal to 1.5 (SqrRoot) ULN
  • Exceptions:

    • Cytopenias due to underlying disease (i.e. potentially reversible with anti-neoplastic therapy); A subject will not be excluded because of cytopenia due to disease, based on the results of bone marrow studies.
    • Known active or chronic human immunodeficiency virus (HIV) or hepatitis C virus (HCV) infection, or positive hepatitis B (Hep B) surface antigen. Prior hepatitis infection that has been treated with highly effective therapy with no evidence of residual infection and with normal liver function (ALT, AST, total and direct bilirubin less than or equal to ULN) is allowed.
    • Hepatobiliary diseases including biliary tract diseases, autoimmune hepatitis, inflammation, fibrosis, cirrhosis of liver caused by viral, alcohol, or genetic reasons. Gilbert's disease is allowed if TBil is less than or equal to 1.5 x ULN.

      • Cardiac ejection fraction greater than or equal to 50%, and QTcF < 450 ms (male) or <470 ms (female) on ECG at Baseline. (Fridericia's Formula: QTcF = (QT)/RR0.33)
      • Contraception: Women of child-bearing potential must agree to use an effective method of birth control during treatment and for 1 month after receiving their last dose of study drug. Fertile men must also agree to use an acceptable method of birth control while on study drug and for at least one week after last dose.


  • Individuals who are pregnant or breast feeding or who become pregnant while enrolled on this trial will be excluded from participation, due to the unknown effects of PLX3397 on a growing fetus or newborn child.
  • Individuals with malignant peripheral nerve sheath tumors will not be eligible to participate in the phase II portion of the trial.
  • Ongoing treatment with any other cancer therapy or investigational agent, with the exception of IT chemotherapy for leukemia, when indicated.
  • Individuals who require therapy with warfarin.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Active untreated infection.
  • Known chronic Hepatitis B or C, or HIV infection.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to PLX3397 or other agents used in study.
  • Patients with PT and/or INR higher than or equal to 1.5 time upper limit of normal, unless patients have lupus anticoagulant in which case they are eligible if cleared by hematology.
  • Drugs that strongly inhibit or potentiate CYP3A4:

    • During Phase I: patients who have received these drugs within 14 days or within 5 half-lives of the drug (whichever is longer) prior to study initiation will be excluded.
    • During Phase II: These drugs should be avoided if possible, as these drugs could increase or decrease blood levels of PLX3397.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02390752

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Contact: Elaine W Thomas (240) 858-7013
Contact: Rosandra N Kaplan, M.D. (240) 760-6198

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United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    888-624-1937      
Sponsors and Collaborators
National Cancer Institute (NCI)
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Principal Investigator: Rosandra N Kaplan, M.D. National Cancer Institute (NCI)
Additional Information:
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Responsible Party: National Cancer Institute (NCI) Identifier: NCT02390752    
Other Study ID Numbers: 150093
First Posted: March 18, 2015    Key Record Dates
Last Update Posted: July 18, 2022
Last Verified: May 12, 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: .All IPD recorded in the medical record will be shared with intramural investigators upon request. All collected IPD will be shared with collaborators under the terms of collaborative agreements.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Clinical data available during the study and indefinitely.
Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Maximum Tolerated Dose
Dose Escalation
Acute Lymphocytic Leukemia
Acute Myelogenous Leukemia
Additional relevant MeSH terms:
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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neurofibromatosis 1
Neurofibroma, Plexiform
Leukemia, Promyelocytic, Acute
Neoplasms by Histologic Type
Leukemia, Lymphoid
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Nerve Sheath Neoplasms
Neoplasms, Nerve Tissue
Neoplastic Syndromes, Hereditary
Neurocutaneous Syndromes
Nervous System Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Peripheral Nervous System Diseases
Neuromuscular Diseases
Peripheral Nervous System Neoplasms
Nervous System Neoplasms
Leukemia, Myeloid, Acute
Leukemia, Myeloid