Purpose

This phase II Pediatric MATCH trial studies how well ensartinib works in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with ALK or ROS1 genomic alterations that have come back (recurrent) or do not respond to treatment (refractory) and have spread to other places in the body (advanced). Ensartinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Category

IRB Number
20170688HU
NCT Number
NCT03213652
Sponsor
National Cancer Institute (NCI) -



Study Contact

Principal Investigator
Anne-Marie Langevin

Virginia Diaz
210-562-9149
diazvr@uthscsa.edu

Jaclyn Hung
210-450-5358
hungj@uthscsa.edu



Eligibility

Eligible Ages
Between 12 Months and 21 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

    - Patient must have enrolled onto APEC1621SC and must have been given a treatment assignment to Molecular Analysis for Therapy Choice (MATCH) to APEC1621F based on the presence of an actionable mutation - Patients must have a body surface area >= 0.5 m^2 at enrollment - Patients must have radiographically measurable disease at the time of study enrollment; patients with neuroblastoma who do not have measurable disease but have iobenguane (MIBG) positive (+) evaluable disease are eligible; measurable disease in patients with CNS involvement is defined as tumor that is measurable in two perpendicular diameters on magnetic resonance imaging (MRI) and visible on more than one slice - Note: The following do not qualify as measurable disease: - Malignant fluid collections (e.g., ascites, pleural effusions) - Bone marrow infiltration except that detected by MIBG scan for neuroblastoma - Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as noted for neuroblastoma - Elevated tumor markers in plasma or cerebrospinal fluid (CSF) - Previously radiated lesions that have not demonstrated clear progression post radiation - Leptomeningeal lesions that do not meet the measurement requirements for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 - Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age - Note: Neurologic deficits in patients with CNS tumors must have been relatively stable for at least 7 days prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score - Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment; if after the required timeframe, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately - Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive: >= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea) - Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil counts [ANC] counts): >= 7 days after the last dose of agent - Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1 - Corticosteroids: if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid - Hematopoietic growth factors: >=14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor; for growth factors 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 and the study-assigned research coordinator - Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors) - Stem cell Infusions (with or without total body irradiation [TBI]): - Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: >= 84 days after infusion and no evidence of graft versus host disease (GVHD) - Autologous stem cell infusion including boost infusion: >= 42 days - Cellular therapy: >= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.) - Radiation therapy (XRT)/external beam irradiation including protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial none marrow (BM) radiation - Note: Radiation may not be delivered to "measurable disease" tumor site(s) being used to follow response to subprotocol treatment - Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42 days after systemically administered radiopharmaceutical therapy - Patients must not have received prior exposure to ensartinib; prior treatment with other ALK inhibitors is permitted given that at least 5 half-lives or 21 days have elapsed since therapy discontinuation, whichever is greater - For patients with solid tumors without known bone marrow involvement: - Peripheral absolute neutrophil count (ANC) >= 1000/mm^3 - Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) - Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity - Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 (within 7 days prior to enrollment) or a serum creatinine based on age/gender as follows (within 7 days prior to enrollment): - Age 1 to < 2 years: maximum serum creatinine 0.6 mg/dL for male and 0.6 mg/dL for female - Age 2 to < 6 years: maximum serum creatinine 0.8 mg/dL for male and 0.8 mg/dL for female - Age 6 to < 10 years: maximum serum creatinine 1 mg/dL for male and 1 mg/dL for female - Age 10 to < 13 years: maximum serum creatinine 1.2 mg/dL for male and 1.2 mg/dL for female - Age 13 to < 16 years: maximum serum creatinine 1.5 mg/dL for male and 1.4 mg/dL for female - Age >= 16 years: maximum serum creatinine 1.7 mg/dL for male and 1.4 mg/dL for female - Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment) - Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (within 7 days prior to enrollment) (for the purpose of this study, the ULN for SGPT is 45 U/L) - Serum albumin >= 2 g/dL (within 7 days prior to enrollment) - Patients must be able to swallow intact capsules - All patients and/or their parents or legally authorized representatives must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines

Exclusion Criteria

    - Pregnant or breast-feeding women will not be entered on this study because there is currently no available information regarding human fetal or teratogenic toxicities; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study treatment and for one week after the last dose of ensartinib - Concomitant medications - Corticosteroids: patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible; if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid - Investigational drugs: patients who are currently receiving another investigational drug are not eligible - Anti-cancer agents: patients who are currently receiving other anti-cancer agents are not eligible - Anti-GVHD agents post-transplant: patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial - CYP3A4 agents: patients who are currently receiving drugs that are strong inducers or strong inhibitors of CYP3A4 are not eligible; strong inducers or inhibitors of CYP3A4 should be avoided from 14 days prior to enrollment to the end of the study - Note: CYP3A4 inducing anti-epileptic drugs and dexamethasone for CNS tumors or metastases, on a stable dose, are allowed - Patients who have an uncontrolled infection are not eligible - Patients who have received a prior solid organ transplantation are not eligible - Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
N/A
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)
Condition
  • Hematopoietic and Lymphoid Cell Neoplasm
  • Malignant Solid Neoplasm
  • Recurrent Ependymoma
  • Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
  • Recurrent Hepatoblastoma
  • Recurrent Langerhans Cell Histiocytosis
  • Recurrent Malignant Germ Cell Tumor
  • Recurrent Malignant Glioma
  • Recurrent Medulloblastoma
  • Recurrent Neuroblastoma
  • Recurrent Non-Hodgkin Lymphoma
  • Recurrent Osteosarcoma
  • Recurrent Rhabdomyosarcoma
  • Recurrent Soft Tissue Sarcoma
  • Recurrent WHO Grade II Glioma
  • Refractory Ependymoma
  • Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
  • Refractory Hepatoblastoma
  • Refractory Langerhans Cell Histiocytosis
  • Refractory Malignant Germ Cell Tumor
  • Refractory Malignant Glioma
  • Refractory Medulloblastoma
  • Refractory Neuroblastoma
  • Refractory Non-Hodgkin Lymphoma
  • Refractory Osteosarcoma
  • Refractory Rhabdomyosarcoma
  • Refractory Soft Tissue Sarcoma
  • Wilms Tumor

    • Arm Groups

    ArmDescriptionIntervention
    Experimental

    Treatment (ensartinib)

    		Patients receive ensartinib PO QD on days 1-28. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.
  • Drug: Ensartinib

    Given PO

    Other names:

    • X-396

  • Other: Pharmacological Study

    Correlative studies

  • Other: Laboratory Biomarker Analysis

    Correlative studies

    •