Long Term Continuous Infusion ch14.18/CHO Plus s.c. Aldesleukin (IL-2)

• Status: Active, not recruiting
• Trial end date: 2020-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The main aim of this clinical trial is to find a way of giving ch14.18/CHO, in combination with subcutaneous aldesleukin (IL-2) and oral isotretinoin (13-cis-RA), to children and young people with primary refractory or relapsed neuroblastoma without intravenous morphine.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: St. Anna Kinderkrebsforschung
• Collaborators: Alder Hey Children's NHS Foundation Trust; Centre Leon Berard; Children's University Hospital, Ireland; Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico; Fondazione IRCCS Istituto Nazionale dei Tumori, Milano; Great Ormond Street Hospital for Children NHS Foundation Trust; Gustave Roussy, Cancer Campus, Grand Paris; Hospital Infantil Universitario Niño Jesús, Madrid, Spain; Hospital Universitario La Fe; Institut Curie; Istituto Giannina Gaslini; Jena University Hospital; Johann Wolfgang Goethe University Hospital; Medical University Innsbruck; Medical University of Graz; Newcastle-upon-Tyne Hospitals NHS Trust; NHS Greater Glasgow and Clyde; Schneider Children's Medical Center, Israel; St. Anna Children's Hospital, Vienna; The Leeds Teaching Hospitals NHS Trust; University Hospital Southampton NHS Foundation Trust; University Hospital Tuebingen; University Hospital, Toulouse; University Hospitals Bristol and Weston NHS Foundation Trust; University Medicine Greifswald
• Treatments: Aldesleukin; Antibodies, Monoclonal; Dinutuximab; Interleukin-2; Isotretinoin

Criteria

Inclusion Criteria:

• At study entry patients must be > 1 year but <= 21 years of age. NOTE: Patients >21 years but <= 45 years of age, fulfilling the remaining criteria, may be enrolled in the study. These patients will be analysed separately and will not be included in the dose finding schedule algorithm. The purpose for inclusion of the older patients is to enable the collection of tolerability data.

• Patients must be diagnosed with neuroblastoma according to the INSS criteria.

• Must have received at least one previous high dose treatment followed by stem cell rescue after conventional therapy.

• Must fulfil one of the following criteria:

• Patients with stage 4 neuroblastoma on the current high-risk SIOPEN trial (HR-NBL-1/SIOPEN) either with primary refractory disease having had more than two front-line treatments or patients ineligible for the R2 randomization due to major delays after completed high-dose treatments.

• Treated and responding relapse after primary stage 4 disease, without signs of progression at study entry

• Treated and responding disseminated relapse after primary localized neuroblastoma without signs of progression at study entry.

• Patients must have a performance status greater or equal 70% (Lansky Score or Karnofsky, see Appendix 1: performance Scales , page 91)

• Patients must have an estimated life expectancy of at least 12 weeks.

• Patients must consent to the placement of a central venous line, if one has not already been placed.

• Patients must be off any standard or experimental treatments for at least two weeks prior to study entry and be fully recovered from the short term major toxic effects.

• Patients must have no immediate requirements for palliative chemotherapy, radiotherapy or surgery.

• At least 4 weeks after major surgery (e.g. laporotomy or thoracotomy) and fully recovered from any post-surgical complications.

• HIV and Hepatitis B negative.

• Females of childbearing potential must have a negative pregnancy test. Patients of childbearing potential must agree to use an effective birth control method. Female patients who are lactating must agree to stop breast-feeding.

• Patients may have had prior CNS metastasis providing the following criteria are all met:

• the patient's CNS disease has been previously treated,

• the patient's CNS disease has been clinically stable for four weeks prior to starting this study (assessment must be made clinically and by CT or MRI scan),

• the patient is off steroids for CNS disease for four weeks prior to starting on study and during the course of the study.

• Patients with seizure disorders may be enrolled if on anticonvulsants and are well controlled.

• All patients and/or their parents or legal guardians must sign a written informed consent

• All institutional and national requirements for human studies must be met.

• Laboratory Testing:

• Patients should have a shortening fraction of >= 30 % by Echocardiogram.

• Patients should have FEV1 and FVC >60% of the predicted by pulmonary function tests. Children unable to do PFTs should have no dyspnea at rest and a pulse oximetry >94% on room air.

• All patients must have adequate bone marrow function as defined by ANC >1 10^9/L, platelets >= 50 10^9/L and haemoglobin > 9.0 g/dL.

• Patients must have adequate liver function, as defined by an ALT or AST < 5 x normal and a total bilirubin < 1.0 mg/dL.

• Patients must have adequate renal function, as defined by a serum creatinine <1.5 mg/dL or a creatinine clearance or radioisotope GFR of > 60 mL/minute/1.73m2.

Exclusion Criteria:

• Patients with progressive disease

• Patients who have previously received treatment with ch14.18/SP2/0 and/or ch14.18/CHO.

• Platelet transfusion dependent.

• Patients with significant intercurrent illnesses and/or any of the following:

• Patients with symptoms of congestive heart failure or uncontrolled cardiac rhythm disturbance.

• Patients with significant psychiatric disabilities or uncontrolled seizure disorders.

• Patients with active infections.

• Patients with a clinically significant neurologic deficit or objective peripheral neuropathy (Grade >2) are ineligible.

• Patients with clinically significant, symptomatic, pleural effusions.

• Patients who require, or are likely to require, corticosteroid or other immunosuppressive drugs.

• Concurrent treatment with any non-trial anticancer therapies.