NCT01704872

Brief 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).

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
16

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Jul 2005

Longer than P75 for phase_1

Geographic Reach
3 countries

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2005

Completed
7 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2006

Completed
6.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2012

Completed
7 months until next milestone

First Submitted

Initial submission to the registry

October 8, 2012

Completed
4 days until next milestone

First Posted

Study publicly available on registry

October 12, 2012

Completed
Last Updated

October 22, 2020

Status Verified

October 1, 2020

Enrollment Period

7 months

First QC Date

October 8, 2012

Last Update Submit

October 21, 2020

Conditions

Neuroblastoma

Keywords

NeuroblastomaRefractory neuroblastomach14.18/CHO

Outcome Measures

Primary Outcomes (1)

  • Adverse events as a measure of safety/tolerability

    Reassess the toxicity profile of one treatment cycle with ch14.18 recloned in CHO cells (ch14.18/CHO), when administered as daily eight-hour infusions and accompanied by supportive care measures in particular to prevent pain, fever and allergic reactions according to previously established standards.

    4 weeks (end of cycle 1)

Secondary Outcomes (4)

  • Measure ch14.18/CHO levels

  • Systemic immune modulation

  • ch14.18/CHO immunogenicity

  • Anti-tumour response

Study Arms (1)

dose level finding ch14.18/CHO

EXPERIMENTAL

A dose escalation design based on Phase I rules starting at 10 mg/m2/day ch14.18/CHO. This is 50% below the dose of ch14.18/SP2/0 used in a large cohort of patients. Dose escalation will be adapted to a modified Fibonacci series aiming at 10, 20 and 30 mg/m2 of ch14.18/CHO. Since this study is a bridging study aiming at a reassessment of the toxicity and determination of the pharmacokinetics of ch14.18/CHO, only a limited number of dose escalation steps (3) is implemented in the design.

Drug: ch14.18/CHO

Interventions

ch14.18/CHODRUG
Also known as: Chimeric 14.18 anti-GD2 monoclonal antibody produced in Chinese hamster ovary cells
dose level finding ch14.18/CHO

Eligibility Criteria

Age1 Year - 21 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • 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.
  • +5 more criteria

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

St Anna Kinderspital

Vienna, 1090, Austria

Location

Charite Children's Hospital

Berlin, 13353, Germany

Location

Gaslini Children's Hospital

Genova, 16147, Italy

Location

MeSH Terms

Conditions

Neuroblastoma

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, PeripheralNeuroectodermal Tumors, PrimitiveNeoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Glandular and EpithelialNeoplasms, Nerve Tissue

Study Officials

  • Holger Lode, MD

    Charite Children's Hospital

    PRINCIPAL INVESTIGATOR

  • Ruth Ladenstein, MD

    St. Anna Kinderkrebsforschung

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 8, 2012

First Posted

October 12, 2012

Study Start

July 1, 2005

Primary Completion

February 1, 2006

Study Completion

March 1, 2012

Last Updated

October 22, 2020

Record last verified: 2020-10

Locations

AU(1)DE(1)IT(1)