Suspended

LTIA Phase I/II Dose Schedule Finding Study of ch14.18/CHO Continuous Infusion Combined With Subcutaneous Aldesleukin (IL-2) in Patients With Primary Refractory or Relapsed Neuroblastoma

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What is being tested

ch14.18/CHO

+ Aldesleukin

+ Isotretinoin

Drug
Who is being recruted

Neoplasms+7

+ Neoplasms by Histologic Type

+ Neoplasms, Germ Cell and Embryonal

From 1 to 21 Years
+39 Eligibility Criteria
See all eligibility criteria
How is the trial designed

Treatment Study

Phase 1 & 2
Interventional
Study Start: January 2012
See protocol details

Summary

Principal SponsorSt. Anna Kinderkrebsforschung
Last updated: July 14, 2020
Sourced from a government-validated database.Claim as a partner

Study start date: January 1, 2012

Actual date on which the first participant was enrolled.

Although a lot of children and young people with neuroblastoma can be cured with current standard chemotherapy, sometimes, particularly at relapse the disease no longer responds to standard drugs. Therefore, there is a need to find new drug combinations which will act against neuroblastoma which no longer responds to standard drugs. Ch14.18/CHO has been shown to improve the outcome of patients with neuroblastoma. However, one of the side effects of receiving ch14.18/CHO is severe pain. High doses of intravenous morphine are needed to control the pain and this means that patients must stay in hospital. Results from other clinical trials have shown that giving ch14.18/CHO over a longer time reduces pain, yet the drug still works just as well to fight the neuroblastoma. The clinical trial aims to give ch14.18/CHO over a longer time so that intravenous morphine is not needed and that this treatment regimen can ultimately be given in an outpatient setting. Ch14.18/CHO is a monoclonal antibody. Monoclonal antibodies are made in the laboratory and are designed to bind to specific cancer cells. Ch14.18/CHO was designed to bind to neuroblastoma cells and other cancer cells that express the GD-2 antigen. The GD-2 antigen is expressed by virtually all neuroblastoma cells. An antigen is a substance that stimulates an immune response in the body by producing antibodies. Thus, when ch14.18/CHO binds to the neuroblastoma cells, the body's immune system is stimulated to attack and kill the neuroblastoma cells. Ch14.18/CHO is called chimeric, because it was genetically engineered to consist of 30% mouse-protein and of 70% human protein. Ch14.18/CHO represents a new kind of cancer therapy that, unlike chemotherapy and radiation, targets the destruction of cancer cells without destroying nearby healthy cells. There is laboratory evidence to suggest that ch14.18/CHO can activate the body's own immune cells to destroy cancer cells. These immune cells include killer cells that are activated or stimulated by aldesleukin (IL-2). Therefore this treatment is a combination of ch14.18/CHO and aldesleukin (IL-2). Aldesleukin (IL-2) is a substance that is similar to a substance made by the body in all individuals. Under normal circumstances, the body makes small amounts of aldesleukin (IL-2) that help white blood cells fight infection. It is now possible to make aldesleukin (IL-2) in the laboratory and give humans much higher doses than their own body makes. There is evidence in the laboratory and in animals that aldesleukin (IL-2) increases the anti-cancer effect of monoclonal antibodies like ch14.18/CHO. We wish to study whether aldesleukin (IL-2) can help improve the effectiveness of ch14.18/CHO in humans. In addition to ch14.18/CHO and aldesleukin (IL-2), isotretinoin (13-cis-RA) will also be given. Isotretinoin (13-cis-RA) is considered standard treatment for patients with neuroblastoma and works by induction of neuroblastoma cell death.

NCT01701479
Principal SponsorSt. Anna Kinderkrebsforschung
Last updated: July 14, 2020
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details

288 patients to be enrolled

Total number of participants that the clinical trial aims to recruit.

Treatment Study

These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria

Any sex

Biological sex of participants that are eligible to enroll.

From 1 to 21 Years

Range of ages for which participants are eligible to join.

Healthy volunteers not allowed

If individuals who are healthy and do not have the condition being studied can participate.

Conditions

Pathology

NeoplasmsNeoplasms by Histologic TypeNeoplasms, Germ Cell and EmbryonalNeoplasms, Glandular and EpithelialNeoplasms, Nerve TissueNeuroectodermal TumorsNeuroectodermal Tumors, Primitive, PeripheralNeuroectodermal Tumors, PrimitiveNeoplasms, NeuroepithelialNeuroblastoma

Criteria

28 inclusion criteria required to participate
All institutional and national requirements for human studies must be met
All patients and/or their parents or legal guardians must sign a written informed consent
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/dL
At least 4 weeks after major surgery (e.g. laporotomy or thoracotomy) and fully recovered from any post-surgical complications
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11 exclusion criteria prevent from participating
Concurrent treatment with any non-trial anticancer therapies
Patients who have previously received treatment with ch14.18/SP2/0 and/or ch14.18/CHO
Patients who require, or are likely to require, corticosteroid or other immunosuppressive drugs
Patients with a clinically significant neurologic deficit or objective peripheral neuropathy (Grade > 2) are ineligible
Show More Criteria

Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.
Treatment Groups
Study Objectives

2 intervention groups are designated in this study

This study does not include a placebo group 

Treatment Groups

Group I

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.

Group II

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.

Study Objectives

Primary Objectives

Secondary Objectives

Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.

This study has 14 locations

St. Anna Kinderspital

Vienna, AustriaOpen St. Anna Kinderspital in Google Maps

Institut Curie

Paris, France

Institut Gustave Roussy

Villejuif, France

University Children's Hospital

Greifswald, Germany
Suspended14 Study Centers