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 ...

• Register: ClinicalTrials.gov
• Last refreshed on: 11 March 2024
• Main ID: NCT02390752
• Date of registration: 17/03/2015
• Prospective Registration: Yes
• Primary sponsor: National Cancer Institute (NCI)
• Public title: 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 ...
• Scientific title: Phase I Trial of TURALIO (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 (TGCT)
• Date of first enrolment: April 29, 2015
• Target sample size: 54
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT02390752
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Rosandra N Kaplan, M.D.
• Affiliation: National Cancer Institute (NCI)

• Name: Elaine W Thomas

Key inclusion & exclusion criteria

- INCLUSION CRITERIA:

- Diagnosis:

- 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 gliomas 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).

- Patients must have relapsed after or be refractory to effective standard
therapies. There are no limits on number of prior therapeutic regimens.

- Disease status: 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.

- 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.

- Patients 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. 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 >= 50% radiation of pelvis; >= 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: >= 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: >= 14 days from surgery

- Others: >= 7 days from last dose of short active hematopoietic growth factors, i.e.
filgrastim, >= 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 TURALIO(R).

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

- Absolute neutrophil count >= 1.5 x 10^9/L

- Hemoglobin > 10 g/dL

- Platelet count >= 100 x 10^9/L

- AST and ALT <= upper limit of normal (ULN)

- TBil and DBil <= ULN with an exception of patients with confirmed Gilbert's syndrome.
For patients with confirmed Gilberts syndrome, the TBil should be <= 1.5 x ULN

- Serum creatinine <= 1.5 x 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 <= 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 <= 1.5 x ULN.

- Cardiac ejection fraction >= 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.

EXCLUSION CRITERIA:

- 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 ag


Age minimum: 3 Years
Age maximum: 35 Years
Gender: All

Health Condition(s) or Problem(s) studied

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Sarcoma

Leukemia, Promyelocytic, Acute

Neurofibroma, Plexiform

Intervention(s)

Drug: TURALIO(R)

Primary Outcome(s)

Phase I: determine a phase II dose of TURALIO(R) [Time Frame: first cycle]

Secondary Outcome(s)

Tolerability [Time Frame: each cycle]

Correlative analysis of immune endpoints with response [Time Frame: before C1 and then C1D7 and then at each restaging evaluation]

Safety [Time Frame: prior to cycles 3,5,9, 13 and every 6 cycles]

To characterize the pharmacokinetic profile [Time Frame: Cycle 1 and 2]

Secondary ID(s)

15-C-0093

150093

Source(s) of Monetary Support

Please refer to primary and secondary sponsors