ch14.18/CHO Bridging Study

• Status: Completed
• Trial end date: 2012-03-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to assess the safety, pharmacokinetic and activity profiles of the ch14.18 antibody produced in cells of hamster origin (ch14.18/CHO).

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

Details

• Lead Sponsor: St. Anna Kinderkrebsforschung
• Collaborators: Charite University, Berlin, Germany; Istituto Giannina Gaslini; St. Anna Children's Hospital, Vienna
• Treatments: Antibodies; Antibodies, Monoclonal; Dinutuximab

Criteria

Inclusion Criteria:

• Patients must be <= 21 years of age.

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

• Disease must be considered refractory to conventional therapy including patients:

• over 1 year of age and presenting as stage 4 disease which have been refractory to first line chemotherapy

• over 1 year with recurrent disease after multi-agent chemotherapy (including any stage and biological pattern)

• If the patient history meets the above criteria, any disease states except overt progressing disease at the time of antibody treatment renders the patients eligible for this study.

• Patients may not have developed human anti-chimeric antibody due to pre-treatment with ch14.18/SP2/0.

• Patients must have a performance status greater or equal 70% (Lansky Score).

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

• Patients must consent to the placement of a central venous line (Broviac or Hickman catheter), if one has not already been placed, or a stable IV anticipated to last for the 5 days required to administer the 5 infusions each month

• Patients must have fully recovered the toxic effects of any prior therapy.

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

• Patients may have had prior CNS metastasis providing, 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), and 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 anti-convulsants and are well controlled.

• Patients should have a shortening fraction of >= 27% by Echocardiogram or ejection function of >50% by gated radionuclide study.

• Patients should have FEV1 and FVC >60% of 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 >1000/uL, platelets >= 75,000/uL and haemoglobin >= 9.0 gm/dL. Transfusions are permitted to meet these platelet and haemoglobin criteria.

• 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 creatinin <= 1.5 mg/dL or a creatinin clearance or radioisotope GFR of >= 60 mL/minute.

• 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.

Exclusion Criteria:

• Patients who have received chemotherapeutic agents (standard or experimental), radiation therapy, or other immunosuppressive therapy within three weeks prior to study.

• Females of childbearing potential will be excluded if they are pregnant, nursing, or not using effective contraception during the treatment period, as the potential effects of ch14.18 on the fetus have not been determined.

• Patients with significant intercurrent illnesses

• 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 or active peptic ulcer, unless these conditions are corrected or controlled.

• 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 for intercurrent disease.

• Patients who have had major surgery, i.e. laparotomy or thoracotomy) within the past two weeks.

• Patients with organ allografts, including bone marrow or haematopoietic stem cells. Patients receiving prior autologous bone marrow or stem cell reinfusions are eligible.

• Patients must be tested for HIV and Hepatitis B Surface (HBS) Ag and excluded, if positive, as this may influence the ability of the immune system to be stimulated by this treatment.