Long Term Continuous Infusion ch14.18/CHO Plus s.c. Aldesleukin (IL-2) (LTI)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01701479|
Recruitment Status : Unknown
Verified October 2012 by St. Anna Kinderkrebsforschung.
Recruitment status was: Recruiting
First Posted : October 5, 2012
Last Update Posted : October 8, 2012
|Condition or disease||Intervention/treatment||Phase|
|Neuroblastoma||Drug: ch14.18/CHO Drug: Aldesleukin Drug: Isotretinoin||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A 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|
|Study Start Date :||November 2010|
|Estimated Primary Completion Date :||March 2013|
|Estimated Study Completion Date :||December 2013|
Experimental: dose schedule finding ch14.18/CHO
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.
Other Name: Chimeric 14.18 anti-GD2 monoclonal antibody produced in Chinese hamster ovary cells
- Efficacy endpoint [ Time Frame: day 15 of first cycle ]
On day 15 of the first cycle in ≥ 80% of patients:
- an increase of 500% and/or an absolute minimum increase to ≥100 cells/mcLof the CD16/CD56 positive activated NK cells, AND
- a measurable ch14.18/CHO level of at least 1 µg/ml.
- Pain-toxicity endpoint [ Time Frame: Day 5 of ch14.18/CHO infusion cycle 1 ]i.v. morphine free ch14.18/CHO infusion schedule after the first 5 days during the first cycle in >= 80% of patients
- ADCC and activated NK cell concentrationsADCC and activated NK cell concentrations above baseline levels in ≥ 80% of patients.
- Soluble IL-2 receptor and CDCAppearance of soluble IL-2 receptor and CDC.
- HAMA and HACADetection of anti-idiotype response by appearance of HAMA and HACA.
- Absolute lymphocyte countIncrease of absolute lymphocyte counts by 50% over baseline.
- Absolute NK cell numbersIncrease of absolute NK cell numbers >1000 cells/mcL in ≥80% of patients.
- Ch14.18/CHO concentrations
- Anti-tumour responseAnti-tumour response in patients with measureable disease (bone marrow, skeletal lesions, soft tissue lesions, lymph nodes and/or primary tumour site) as measured by immunocytology, MIBG, CT and/or MRI.
- Confirmation cohortOnce the dose finding stage is completed we will recruit a further 20 patients to the same dose level to confirm the primary and secondary endpoints.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01701479
|Contact: Ruth Ladenstein, MDfirstname.lastname@example.org|
|Contact: Holger Lode, MD, PhDemail@example.com|
|St. Anna Kinderspital||Recruiting|
|Vienna, Austria, 1090|
|Contact: Ruth Ladenstein, MD +43(1)40470-4750 firstname.lastname@example.org|
|Principal Investigator: Ruth Ladenstein, MD|
|Paris, France, 75248|
|Contact: Jean Michon, MD +33-1-44-35-4550 email@example.com|
|Principal Investigator: Jean Michon, MD|
|Sub-Investigator: Daniel Orbach, MD|
|Institut Gustave Roussy||Recruiting|
|Villejuif, France, 94805|
|Contact: Dominique Valteau-Couanet, MD +33-1-42114872 firstname.lastname@example.org|
|Principal Investigator: Dominique Valteau-Couanet, MD|
|Sub-Investigator: Angela Digiannatale, MD|
|University Children's Hospital||Recruiting|
|Greifswald, Germany, 17475|
|Contact: Holger Lode, MD, PhD +49 3834 866301 email@example.com|
|Principal Investigator: Holger Lode, Md, Phd|
|Schneider Children's Medical Centre of Israel||Recruiting|
|Petach Tikvah, Israel, 49202|
|Contact: Isaac Yaniv, MD +972-3-9253669 firstname.lastname@example.org|
|Principal Investigator: Isaac Yaniv, MD|
|Sub-Investigator: Shifra Ash, MD|
|Gaslini Children's Hospital||Recruiting|
|Genova, Italy, 16147|
|Contact: Alberto Garaventa, MD +39-010-5636694-714 email@example.com|
|Principal Investigator: Alberto Garaventa, MD|
|Sub-Investigator: Carla Manzitti, MD|
|Hospital Universitario La Fe||Recruiting|
|Valencia, Spain, 46009|
|Contact: Victoria Castel, MD +34-96-197-3304 firstname.lastname@example.org|
|Principal Investigator: Victoria Castel, MD|
|Sub-Investigator: Adela Canete, MD|
|Birmingham Children's Hospital NHS Foundation Trust||Not yet recruiting|
|Birmingham, United Kingdom, B4 6NH|
|Contact: Pamela Kearns, MBChB, MRCP (paeds), PhD +44121 3338238 email@example.com|
|Principal Investigator: Pamela Kearns, MBChB, MRCP (paeds), PhD|
|University Hospitals Bristol NHS Foundation Trust||Not yet recruiting|
|Bristol, United Kingdom, BS2 8BJ|
|Contact: Helen Rees, MBBS, MRCP(Paeds), DCH +44117 342 28815 Helen.firstname.lastname@example.org|
|Principal Investigator: Helen Rees, MBBS, MRCP(Paeds), DCH|
|Leeds Teaching Hospitals NHS Trust||Not yet recruiting|
|Leeds, United Kingdom, LS1 3EX|
|Contact: Martin Elliott, MBChB, MRCP, PhD +44113 3928039 Martin.email@example.com|
|Principal Investigator: Martin Elliott, MBChB, MRCP, PhD|
|Alder Hey Children's NHS Foundation Trust||Not yet recruiting|
|Liverpool, United Kingdom, L12 2AP|
|Contact: Lisa Howell, B.Med.Sci, BmBs, MRCPCH +441512525976 Lisa.firstname.lastname@example.org|
|Principal Investigator: Lisa Howell, B.Med.Sci, BmBs, MRCPCH|
|University College Hospitals NHS Foundation Trust||Not yet recruiting|
|London, United Kingdom, NW1 2BU|
|Contact: Ananth Shankar, DCH, MD, MRCP +44845 1555000 ext 79490 email@example.com|
|Principal Investigator: Ananth Shankar, DCH, MD, MRCP|
|Great Ormond Street Hospital for Children NHS Foundation Trust||Not yet recruiting|
|London, United Kingdom, WC1N 3JH|
|Contact: John Anderson, MBBS, MRCP (Paeds), PhD +442074059200 ext 8832 firstname.lastname@example.org|
|Principal Investigator: John Anderson, MBBS, MRCP (Paeds), PhD|
|The Newcastle upon Tyne Hospitals NHS Foundation Trust||Not yet recruiting|
|Newcastle, United Kingdom, NE1 4LP|
|Contact: Deborah Tweddle, MBChB (Hons), PhD, FRCPCH +44191 2824068 email@example.com|
|Principal Investigator: Deborah Tweddle, MBChB (Hons), PhD, FRCPCH|
|Principal Investigator:||Holger Lode, MD, PhD||University Medicine Greifswald|