PLX3397 in Children and Young Adults With Refractory Leukemias and Refractory Solid Tumors Including Neurofibromatosis Type 1 (NF1) Associated Plexiform Neurofibromas (PN)
This study is currently recruiting participants.
Verified March 3, 2017 by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
First received: March 17, 2015
Last updated: June 30, 2017
Last verified: March 3, 2017
- 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.
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Prolymphocytic, Acute
||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
||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)
Primary Outcome Measures:
- Phase I: determine a phase II dose of PLX3397 [ Time Frame: First cycle ]
- Phase II: determine antitumor activity of PLX3397 in patients with NF1 PN [ Time Frame: At each response evaluation ]
Secondary Outcome Measures:
- To study PK [ Time Frame: Cycles 1 and 2 ]
- Determine effect of PLX 3397 on circulating [ Time Frame: Before C1 and then C1D7 and then at each restaging evaluationevaluationbiomarkers ]
- Evaluate biologic activity and extended tolerability of PLX3397 [ Time Frame: Each cycle ]
- Evaluated patient reported and functional outcomes [ Time Frame: Prior to cycles 3,5,9,13 and every 6 cycles ]
| Estimated Enrollment:
| Study Start Date:
||March 6, 2015
| Estimated Study Completion Date:
||December 1, 2018
| Estimated Primary Completion Date:
||December 1, 2017 (Final data collection date for primary outcome measure)
Take oral drug daily for 28 day cycle
Take oral drug daily for a 28 day cycle
|Ages Eligible for Study:
||3 Years to 35 Years (Child, Adult)
|Sexes Eligible for Study:
|Accepts Healthy Volunteers:
Enrollment in the cohort of patients with NF1 inoperable plexiform neurofibromas (PN) is temporarily suspended as of Amendment G as requested by the FDA due to IND Safety Report of 07 October 2016. Patient accrual of patients with NF1 and MPNST may continue in the Phase I Portion.
- 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 temporarily suspended as requested by the FDA due to IND Safety Report of 07 October 2016
- 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 refractory leukemia must have M2 or M3 bone marrow.
--Phase II: Patients must have measurable disease.Phase II temporarily suspended as requested by the FDA due to IND Safety Report of 07 October 2016
Age (must have BSA greater than or equal to 0.55 m2):
- 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
- Informed Consent: All patients or their legal guardians (if the patient is<18 years old) must sign an IRB-approved document of informed consent to demonstrate their understanding of the investigational nature and the risks of this study before any protocol-related studies are performed. When appropriate, pediatric subjects will be included in all discussions.
- 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.
Patients must have fully recovered (to Grade 1) from the acute toxic effects of all prior anti-cancer therapy.
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, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02390752
|National Institutes of Health Clinical Center, 9000 Rockville Pike
|Bethesda, Maryland, United States, 20892 |
National Cancer Institute (NCI)
||Rosandra N Kaplan, M.D.
||National Cancer Institute (NCI)
||National Cancer Institute (NCI)
History of Changes
|Other Study ID Numbers:
|Study First Received:
||March 17, 2015
||June 30, 2017
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Maximum Tolerated Dose
Acute Lymphocytic Leukemia
Acute Myelogenous Leukemia
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on August 17, 2017
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Nerve Sheath Neoplasms
Neoplasms by Histologic Type
Immune System Diseases
Neoplasms, Nerve Tissue
Neoplastic Syndromes, Hereditary
Nervous System Diseases
Heredodegenerative Disorders, Nervous System
Genetic Diseases, Inborn
Peripheral Nervous System Neoplasms
Nervous System Neoplasms
Peripheral Nervous System Diseases