Dose schedule finding study of ch14.18/CHO & Aldesleukin in patients with high-risk neuroblastoma

• Conditions: euroblastoma; MedDRA version: 16.0Level: PTClassification code 10029260Term: NeuroblastomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2009-018077-31-GB
• Lead Sponsor: St. Anna Kinderkrebsforschung

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-05-10
• Last Update Posted: 20 May 2013

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 140

Inclusion Criteria

a) 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.

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

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

d) Must fulfil one of the following criteria:
• Patients with stage 4 neuroblastoma either:
o on the current high-risk SIOPEN trial (HR-NBL-1/SIOPEN) either with primary refractory disease having had two or more front-line treatments or patients ineligible for the R2 randomisation due to major delays after completed high-dose treatments or
o Standard high-risk front-line treatment (other than HR-NBL (1.5)/SIOPEN) consisting of intensive induction, followed by high-dose treatment with stem cell rescue.
• Treated and responding relapse after primary stage 4 disease, without signs of progression at study entry
• Treated and responding disseminated neuroblastoma relapse after having received ASCT without signs of progression at study entry.

e) Patients must have a performance status greater or equal 70% (Lansky Score or Karnofsky)

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

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

h) 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.

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

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

k) HIV and Hepatitis B negative.

l) Females of childbearing potential must have a negative pregnancy test within 7 days prior to enrolment onto the study. Patients of childbearing potential must agree to use an effective birth control method. Female patients who are lactating must agree to stop breast-feeding.

m) Patients may have had prior CNS metastasis providing the following criteria are all met:
a. the patient’s CNS disease has been previously treated,
b. 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),
c. the patient is off steroids for CNS disease for four weeks prior to starting on study and during the course of the study.

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

o) All patients and/or their parents or legal guardians must sign a written informed consent.

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

q) 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 dyspnoea 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

Exclusion Criteria

a) Patients with progressive disease.

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

c) Platelet transfusion dependent.

d) 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 or pericardial effusions or ascites.
e) Patients who require, or are likely to require, corticosteroid or other immunosuppressive drugs.
f) Concurrent treatment with any non-trial anticancer therapies.

Study & Design

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