Pediatric patients with relapsed neuroblastoma MedDRA version: 19.1 Level: PT Classification code 10066595 Term: Neuroblastoma recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: recombinant chimeric monoclonal antibody ch14.18
Product Code: ch14.18
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: not applicable
Other descriptive name: chimeric mon
Sponsors
University Children´s Hospital Tübingen,
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Less than or equal to 21 years of age. • Histologically confirmed neuroblastoma. • Refractory to standard treatment (i.e. refractory disease) or relapse after previous autologous or allogenic stem cell transplantation. • Patient has undergone haploidentical stem cell transplantation prior to antibody infusion according to appendix IV at least 60 days prior to starting immunotherapy. • Serum glutamate pyruvate transaminase (SGPT) less than 2.5 times the upper limit of normal for age and total bilirubin less than 2 times the upper limit of normal for age. D-Dimers less than 2 times the upper limit of normal. • Creatinine clearance or radioisotope GFR greater than or equal to 40 ml/min/1.73m2. • Cardiac shortening fraction greater than or equal to 20% by echocardiogram. • Karnofsky/Lansky performance score (age appropriate) of greater than or equal to 50. • 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. • Written informed consent is obtained, and for minors a written agreement by parents or legal guardian. • All institutional and national requirements for human studies are met. Are the trial subjects under 18? yes Number of subjects for this age range: 60 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Marked baseline prolongation of QT/QTc interval (e.g. demonstration of a QTc interval > 450 milliseconds). • 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 acute GvHD Grade III or IV or extensive chronic GvHD. • Patients with clinically significant, symptomatic, pleural effusions. • Patients who have had major surgery, (i.e. laparotomy or thoracotomy) within the past two weeks. • Patients who will more than 12 months post haploidentical stem cell transplantation at the time of starting the first cycle of immunotherapy. • Prior administration of ch14.18 antibody. • HIV or Hepatitis B Surface (HBS) Ag positive. As presence of either may influence the ability if the immune system to be stimulated by this treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • Evaluation of safety and feasibility of the chimeric 14.18 anti-GD2 monoclonal antibody (ch14.18/CHO) in combination with subcutaneous aldesleukin (IL-2, (Proleukin®) ;Secondary Objective: • To evaluate the anti-tumour responses resulting from this immunotherapy regimen through clinical assessments (radiographic and clinical measurements, including bone marrow immunohistochemistry for those research participants with marrow involvement). • To evaluate pharmacokinetics of the ch14.18/CHO. • To evaluate changes in NK cell activation and proliferation (immunological monitoring). ;Primary end point(s): Primary endpoint is "success of treatment" defined as a patient receiving the full protocol treatment, still alive 180 days after end of treatment without progression and without unacceptable toxicity and acute GvHD ? Grade III or extensive chronic GvHD. Thus, a composite variable is used as primary endpoint: Treatment success, is defined as a patients who did not experience 1. unacceptable toxicities 2. acute GvHD = Grade III or extensive chronic GvHD 3. other toxicities that did not recover to ? Grade 1 within 4 weeks or 4. progressive disease after 6 cycles or 5. deaths within treatment after SCT 6. withdrawal due to other reasons ;Timepoint(s) of evaluation of this end point: 180 days after the end of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): rate and type of dose limiting toxicity, Incidence of GvHD, Progression during treatment, Immunological assessment (cytokine levels, NK activity, immunoreconstitution), Event Free Survival, Overall Survival;Timepoint(s) of evaluation of this end point: three years | — |
Countries
Austria, Germany
Contacts
Public ContactPeter Lang
Universitätsklinikum Tübingen
Outcome results
None listed