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

NCT01701479 | Unknown Phase 1 DMC

• 2 other identifiers: 0120102009-018077-31
• Study Type: interventional
• Target: 288
• Locations: 7 countries
• Sites: 14

Brief 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.

Conditions

Neuroblastoma

Keywords

Neuroblastoma; Refractory neuroblastoma; Relapsed neuroblastoma; ch14.18/CHO; Aldesleukin (IL-2)

Outcome Measures

Primary Outcomes (1)

• Event free survival

  The primary endpoint is event free survival calculated from the date of randomisation. The following will be considered as events: * disease progression or relapse * death from any cause * second neoplasm

  through study completion, an average of 1 year

Secondary Outcomes (7)

• Pain-toxicity endpoint

  through study completion, an average of 1 year

• Efficacy endpoint

  through study completion, an average of 1 year

• Systemic immune modulation/response

  through study completion, an average of 1 year

• Assessment of absolute lymphocyte counts and absolute NK cell numbers after the respective cycles as a measurement of response to s.c. aldesleukin (IL-2) in the standard treatment arm.

  through study completion, an average of 1 year

• Determination of pharmacokinetics of ch14.18/CHO by assessing blood levels of ch14.18/CHO via ELISA (Enzyme-linked-Immunosorbent Assay)

  through study completion, an average of 1 year

Study Arms (2)

Experimental arm

EXPERIMENTAL

Subcutaneous aldesleukin (IL-2) will be given at a dose of 6 x 106 IU/m2/day in two 5 day blocks (days 1-5 and 8-12). A continuous infusion of ch14.18/CHO is started on day 8. The duration of the infusion is dependent on the assigned infusion schedule. The duration will range from 10 to 21 days. Three dose levels will be considered with respect to daily dose (7 mg/m2, 10 mg/m2, 15 mg/m2), which relates to total doses of 100 mg/m2,150 mg/m2 and 210 mg/m2. Patients will receive isotretinoin (13-cis-RA) 160 mg/m²/day divided into two equal doses given orally twice a day for 14 days after the completion of the ch14.18/CHO infusion. The starting day is dependent on the duration of ch14.18/CHO infusion and may be either day 19, 23, 24 or 30.

Drug: ch14.18/CHO; Drug: Aldesleukin; Drug: Isotretinoin

Comparator arm

ACTIVE COMPARATOR

A continuous infusion of ch14.18/CHO is started on day 8. The duration of the infusion is dependent on the assigned infusion schedule. The duration will range from 10 to 21 days. Three dose levels will be considered with respect to daily dose (7 mg/m2, 10 mg/m2, 15 mg/m2), which relates to total doses of 100 mg/m2,150 mg/m2 and 210 mg/m2. Patients will receive isotretinoin (13-cis-RA) 160 mg/m²/day divided into two equal doses given orally twice a day for 14 days after the completion of the ch14.18/CHO infusion. The starting day is dependent on the duration of ch14.18/CHO infusion and may be either day 19, 23, 24 or 30.

Drug: ch14.18/CHO; Drug: Isotretinoin

Interventions

ch14.18/CHO DRUG

Also known as: Chimeric 14.18 anti-GD2 monoclonal antibody produced in Chinese hamster ovary cells

Comparator arm; Experimental arm

Aldesleukin DRUG

Also known as: Proleukin, Interleukin-2, IL-2

Experimental arm

Isotretinoin DRUG

Also known as: 13-cis-Retinoic acid, 13-cis-RA

Comparator arm; Experimental arm

Eligibility Criteria

• Age: 1 Year - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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:

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (14)

St. Anna Kinderspital

Vienna, 1090, Austria

Location

Institut Curie

Paris, 75248, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

University Children's Hospital

Greifswald, 17475, Germany

Location

Schneider Children's Medical Centre of Israel

Petach Tikvah, 49202, Israel

Location

Gaslini Children's Hospital

Genova, 16147, Italy

Location

Hospital Universitario La Fe

Valencia, 46009, Spain

Location

Birmingham Children's Hospital NHS Foundation Trust

Birmingham, B4 6NH, United Kingdom

Location

University Hospitals Bristol NHS Foundation Trust

Bristol, BS2 8BJ, United Kingdom

Location

Leeds Teaching Hospitals NHS Trust

Leeds, LS1 3EX, United Kingdom

Location

Alder Hey Children's NHS Foundation Trust

Liverpool, L12 2AP, United Kingdom

Location

University College Hospitals NHS Foundation Trust

London, NW1 2BU, United Kingdom

Location

Great Ormond Street Hospital for Children NHS Foundation Trust

London, WC1N 3JH, United Kingdom

Location

The Newcastle upon Tyne Hospitals NHS Foundation Trust

Newcastle, NE1 4LP, United Kingdom

Location

Related Links

• Related Info
• Related Info

MeSH Terms

Conditions

Neuroblastoma

Interventions

aldesleukin; Interleukin-2; Isotretinoin

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Pigments, Biological

Study Officials

• Holger Lode, MD, PhD

  University Medicine Greifswald

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The patients will be randomised to immunotherapy with isotretinoin (13-cis-RA) and ch14.18/CHO, with or without aldesleukin (IL-2).

Study Record Dates

• First Submitted: October 3, 2012
• First Posted: October 5, 2012
• Study Start: January 1, 2012
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2020
• Last Updated: July 14, 2020

Record last verified: 2020-07

Locations

IT (1); ES (1); DE (1); GB (7); FR (2); AU (1); IL (1)