Phase I Trial of TURALIO(R) (Pexidartinib, PLX3397) in Children and Young Adults With Refractory Leukemias and Refractory Solid Tumors Including Neurofibromatosis Type 1 (NF1) Associated Plexiform Neurofibromas (PN) and Tenosynovial Giant Cell Tumor ...

NCT02390752 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 15009315-C-0093
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Some people with cancer have solid tumors. Others have refractory leukemia. This may not go away after treatment. Researchers want to see if a drug called TURALIO(R) can shrink tumors or stop them from growing. Objectives: \- To find the highest safe dose and side effects of TURALIO(R). To see if it helps treat certain types of cancer. Eligibility: \- People ages 3-35 with a solid tumor or leukemia that has returned or not responded to cancer therapies. Design:

• Individuals will be screened with:
• Medical history
• Physical exam
• Blood and urine tests
• Heart tests
• Scans or other tests of the tumor
• Individuals will take TURALIO(R) 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. Individuals will keep a diary of symptoms.
• Individuals with solid tumors will have scans or x-rays.
• Individuals with leukemia will have blood tests. They may have a bone marrow sample taken.
• Some individuals may have a biopsy.
• When finished taking TURALIO(R), individuals will have follow-up visits. They will repeat the screening tests and note side effects.

Conditions

Neurofibroma, Plexiform; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Promyelocytic, Acute; Sarcoma

Keywords

Maximum Tolerated Dose; Dose Escalation; Acute Lymphocytic Leukemia; Acute Myelogenous Leukemia

Outcome Measures

Primary Outcomes (1)

• Phase I: determine a phase II dose of TURALIO(R)

  Evaluate the safety and tolerability of TURALIO(R)

  first cycle

Secondary Outcomes (4)

• Tolerability

  each cycle

• To characterize the pharmacokinetic profile

  Cycle 1 and 2

• Safety

  prior to cycles 3,5,9, 13 and every 6 cycles

• Correlative analysis of immune endpoints with response

  before C1 and then C1D7 and then at each restaging evaluation

Study Arms (1)

Phase I

EXPERIMENTAL

take oral drug daily for a 28 day cycle

Drug: TURALIO(R)

Interventions

TURALIO(R) DRUG

take oral drug daily for a 28 day cycle

Phase I

Eligibility Criteria

• Age: 3 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis:
• Individuals 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. Individuals 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 gliomas are located in the optic pathway and are typically hypo- or iso-intense on T1 and hyperintense on T2-weighted images.
• In addition, individuals with NF1 and with malignant peripheral nerve sheath tumor (MPNST).
• Individuals must have relapsed after or be refractory to effective standard therapies. There are no limits on number of prior therapeutic regimens.
• Disease status: Individuals 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.
• Age \>= 3 and \<= 35 years of age (must have BSA \>= 0.55 m\^2):
• 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.
• Individuals must be able to swallow capsules.
• Performance Status: Karnofsky \>= 50% for patients \> 16 years of age and Lansky \>= 50% for patients \<= 16 years of age. Individuals who are wheelchair bound because of paralysis will be considered "ambulatory" when they are up in their wheelchair. Individuals have to be able to travel to the NIH for evaluations.
• Prior therapy:
• Individuals 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.

You may not qualify if:

• 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 TURALIO(R) on a growing fetus or newborn child.
• 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 active hepatitis A, B, C or HIV infection, chronic Hepatitis B or C, or HIV infection or inactive Hepatitis B carrier.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to TURALIO(R) or other agents used in study.
• Individuals with PT and/or INR higher than or equal to 1.5 times 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, which includes CYP3A4 inducer, UGT inhibitors and acid reducing agents and avoid concomitant use of PPIs:
• Individuals 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Neurofibroma, Plexiform; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Promyelocytic, Acute; Sarcoma; Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms; Peripheral Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Neoplasms, Connective and Soft Tissue

Study Officials

• Rosandra N Kaplan, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

NCI POB Solid Tumor Referral Team

CONTACT

(240) 858-7012; ncipobstreferrals@mail.nih.gov

Rosandra N Kaplan, M.D.

CONTACT

(240) 760-6198; kaplanrn@mail.nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2015
• First Posted: March 18, 2015
• Study Start: April 29, 2015
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2028
• Last Updated: April 24, 2026

Record last verified: 2026-03-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, 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.

Locations

US (1)