STUDY OF IPILIMUMAB IN CHILDREN, ADOLESCENTS, AND YOUNG ADULTS WITH TREATMENT REFRACTORY CANCER

• Conditions: Sarcoma - Wilm's Tumor - Lymphoma - Neuroblastoma; MedDRA version: 17.1Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2012-001141-41-Outside-EU/EEA
• Lead Sponsor: ational Cancer Institute NCI

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-09-18
• Last Update Posted: 30 March 2015

Recruitment & Eligibility

• Status: A
• Sex: All
• Target Recruitment: 27

Inclusion Criteria

AGE: Patients must be greater than or equal to 2 years and less than or equal to 21 years of age.

DIAGNOSIS: Histologically confirmed solid tumors, which may include but are not limited to rhabdomyosarcoma and other soft tissue sarcomas, Ewing's sarcoma family of tumors, osteosarcoma, neuroblastoma, Wilm's tumor, Hodgkin's or non-Hodgkin's lymphoma.

MEASURABLE/EVALUABLE DISEASE: Patients must have measurable or evaluable tumors.

PRIOR THERAPY:

•The patient's cancer must have relapsed following or failed to respond to standard therapy and/or the patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival.
•Patients must have completed their last dose of chemotherapy, monoclonal antibody, or investigational therapy at least 4 weeks prior to enrollment and patients that received irradiation must have completed therapy at least one week prior to enrollment. Biologic or other approved molecular targeted small molecule inhibitors with a short half-life
must be stopped at least 1 week prior to enrollment. For patients who have undergone autologous stem cell transplantation, at least 3 months must have elapsed since transplant.
•Patients must have recovered from the toxic effects (to a grade 1 or less) of all prior therapy prior to enrollment, with the exception of the following:

?Hematological toxicity: recovery to levels required below
?Low electrolyte levels (Such individuals should receive appropriate supplementation)
?For patients on anticoagulant therapy or with pre-existing coagulation abnormalities, PT, PTT must return to baseline.
?Liver function tests must resolve to values required below
?Grade 3 hypoalbuminemia
?Alopecia
?Sterility
PERFORMANCE STATUS: Patients greater than 10 years old must have a Karnofsky Score of greater than or equal to 50 and children less than 10 years old must have a Lansky score of greater than 50.
HEMATOLOGIC FUNCTION: Patients must have adequate bone marrow function, defined as a peripheral absolute granulocyte count of greater than or equal to 1000/microL, hemoglobin greater than or equal to 8 gm/dl, and a transfusion independent platelet count greater than or equal to 50,000/microL.

HEPATIC FUNCTION: Aspartate transaminase (AST) and alanine transaminase (ALT), less than or equal to 2.5-fold the upper limit of normal (ULN). Normal total bilirubin.

RENAL FUNCTION: Patients must have normal age-adjusted serum creatinine (see table below) OR a creatinine clearance greater than or equal to 70 mL/min/1.73 m(2).

INFECTIOUS DISEASE:

A patient with viral hepatitis (HBV, HCV) or human immunodeficiency virus (HIV) will be excluded from trial to limit confounding variables in the assessment of the potential hepatic toxicity of ipilimumab and uncertain impact of ipilimumab administration on viral replication. Serology will not be required unless infection is clinically suspected. A positive hepatitis B titer does not exclude a patient if immunization has been performed and if there is no history of disease.

INFORMED CONSENT: All patients or their legal guardians (if the patient is less than 18 years old) must sign a document of informed consent (Pediatric Oncology Branch, NCI screening protocol for NIH patients) prior to performing studies to determine patient eligibility. After confirmation of eligibility, all patients or their legal guardians must voluntarily sign the IRB approved protocol specific informe

Exclusion Criteria

•Primary brain tumors
•Clinically significant unrelated systemic illness, such as serious infections or organ dysfunction, which in the judgment of the Principal or Associate Investigators would compromise the patient's ability to tolerate the agents in this trial or are likely to interfere with the study procedures or results. This includes but is not limited to:

?Critically-ill or medically unstable patients
?Patients with active infection or other significant systemic illness
?Patients with active diarrhea
?Patients with active eye inflammation, uveitis
?Presence of a symptomatic pleural effusion
?Patients with symptoms of congestive heart failure or uncontrolled cardiac rhythm disturbance
?History of malignant hyperthermia
?Concurrent or history of autoimmune disease excluding stable asthma
?Positive direct Coombs testing or history of hemolytic anemia
?Patients with a history of ongoing or intermittent bowel obstruction
•Concurrent radiation
•Patients with a history of allogeneic bone marrow transplantation.
•Untreated CNS metastases will render the patient ineligible however patients with a previous history of CNS metastases are eligible if: the metastases have been treated with surgery and/or radiotherapy, are clinically stable as evidenced by no requirements for corticosteroids, the patient has no evolving neurologic deficits and no progression in residual brain abnormalities without specific therapy are eligible one week post radiation or radiosurgery. Patients with asymptomatic subcentemeric CNS lesions will be eligible for trial if no immediate radiation or surgery.
•Patients with a history of previous therapy with ipilimumab will be excluded from study participation.
•Treatment with any of the following immunomodulatory agents within 14 days prior to study entry:
Systemic corticosteroid therapy
Erythropoeisis stimulating agents
Retinoids
Fenretinide
Interferons or interleukins
Cytokine-fusion proteins
Growth hormone
IVIG
•Treatment with myeloid growth factors (GM-CSF or G-CSF) within 72 hours prior to study entry.
•Patients with autoimmune disease, including autoimmune hemolytic anemia, ulcerative and hemorrhagic colitis, endocrine disorders, sarcoid granuloma, myasthenia gravis, polymyositis, and Guillain-Barre syndrome.

•Pregnant or breastfeeding females are excluded because ipilimumab may be harmful to the developing fetus or nursing child.
•Concurrent administration of any other investigational agent.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified