Phase II Study of Monoclonal Antibody ch14.18/CHO Continuous Infusion in Patients With Primary Refractory or Relapsed Neuroblastoma
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|ClinicalTrials.gov Identifier: NCT02743429|
Recruitment Status : Active, not recruiting
First Posted : April 19, 2016
Last Update Posted : October 4, 2021
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|Condition or disease||Intervention/treatment||Phase|
|Neuroblastoma||Drug: dinutuximab beta||Phase 2|
The Treatment with ch14.18 antibody has demonstrated efficacy in patients with neuroblastoma. However the treatment is associated with an on target side effect, i.e. neuropathic pain. This requires coadministration of intravenous morphine.
In this clinical Trial we will evaluate a less toxic treatment regimen consisting of continuous longterm Infusion (LTI) of ch14.18/CHO administered at a dose of 10 mg/m2/day over 10 days (total dose 100 mg/m2/cycle). Patients may receive up to five 35-day cycles in absence of signs of progression.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Study of Monoclonal Antibody ch14.18/CHO Continuous Infusion in Patients With Primary Refractory or Relapsed Neuroblastoma|
|Actual Study Start Date :||March 27, 2015|
|Estimated Primary Completion Date :||December 2023|
|Estimated Study Completion Date :||June 2024|
Experimental: Long term infusion of ch14.18/CHO
10 day continuous Infusion of ch14.18/CHO.
Drug: dinutuximab beta
Up to 5 cycles of continuous infusion of ch14.18/CHO is administered at a dose of 10 mg/m2/day over 10 days (total dose 100 mg/m2/cycle).
Cycle duration: 35-days.
- Anti-tumour activity of ch14.18/CHO continuous infusion [ Time Frame: 2 years ]The response rate in patients with measurable/evaluable disease (skeletal lesions, soft tissue lesions, lymph nodes and/or primary tumour site and bone marrow) as measured by Metaiodobenzylguanidine scan (MIBG), Computed tomography (CT), Magnetic Resonance Imaging (MRI) and/or immunocytology at the end of the study.
- Progression-Free Survival [ Time Frame: 5 years ]
- Safety and tolerability [ Time Frame: 2 years ]
- Pain intensity and the need for appropriate medication for pain relief
- Adverse events, vital signs and changes in clinical laboratory assessments
- Immunogenicity [ Time Frame: 2 years ]Immunogenicity: Anti-Drug Antibody (ADA)
- Immunophenotyping [ Time Frame: 2 years ]Unit: cells/µl
- Antibody dependent cellular cytotoxicity (ADCC) [ Time Frame: 2 years ]Unit: %
- Complement dependent cytotoxicity (CDC) [ Time Frame: 2 years ]Unit: %
- Whole Blood Test (WBT) [ Time Frame: 2 years ]Unit: %
- Cytokines [ Time Frame: 2 years ]Unit: µg/ml
- Clearance (CL) [ Time Frame: 2 years ]Unit: l/d*m²
- Volume distribution at steady state (Vdss) [ Time Frame: 2 years ]Unit: l/m²
- mean residence time (MRT) [ Time Frame: 2 years ]Unit: days
- half-life time (t1/2) [ Time Frame: 2 years ]Unit: days
- Area Under the Curve (AUC) [ Time Frame: 2 years ]Unit: µg*d/ml
- Maximum Plasma Concentration (Cmax) and Minimum Plasma Concentration (Cmin) [ Time Frame: 2 years ]Unit: µg/ml
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|Ages Eligible for Study:||1 Year to 21 Years (Child, Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- ≥ 12 months and ≤ 21 years of age at the time of study entry
- Diagnosis of neuroblastoma according to the INSS criteria
Tumour burden controlled by conventional therapy (except patients with early minimal bone marrow relapse) fulfilling one of the following criteria:
- Primary refractory patients with stage 4 disease
- Relapse after primary stage 4 disease
- Disseminated relapse after primary localized neuroblastoma.
- Measurable and/or evaluable disease in any of the following sites (skeletal lesions, soft tissue lesions, lymph nodes and/or primary tumour site and/or bone marrow) as measured by mIBG scan, CT, MRI and/or immunocytology
- Life expectancy of at least 12 weeks.
- Performance status greater or equal to 70% (Lansky Score or Karnofsky)
- Consent to the placement of a central venous line, if one has not already been placed
- Off any standard or experimental treatment for at least two weeks prior to start of immunotherapy (Day 1 of cycle 1) and fully recovered from the short-term major toxic effects
- No immediate requirements for palliative chemotherapy, radiotherapy or surgery
- At least 2 weeks from any tumour surgery and fully recovered from any post-surgical complications
- HIV sero-negative
- Neither active nor chronic-replicative Hepatitis B infection
Females of childbearing potential must have a negative pregnancy test and must agree to use an effective birth control method during the whole study duration including the last FU visit.
Female patients who are lactating must agree to stop breast-feeding.
Patient may have had prior CNS metastases, provided the following criteria are all met:
- 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).
- The patient is off steroids for four weeks prior to starting trial treatment and will not require them during the course of the study.
- Patients with seizure disorders may be enrolled if well controlled on anticonvulsants and if no seizures have occurred within a 6 week period prior to starting trial treatment
- All patients and/or their parents or legal guardians must sign a written informed consent.
- Shortening fraction of ≥ 30% on Echocardiogram.
- FEV1 and FVC > 60% of the predicted by pulmonary function tests. Children unable to do PFTs should have no dyspnoea at rest and a pulse oximetry > 94% in room air.
- Adequate bone marrow function as defined by ANC >0.5 10^9/L, platelets ≥ 20 10^9/L and haemoglobin > 8.0 g/dL
- Adequate liver function, as defined by an ALT or AST < 5 x normal and a total bilirubin < 1.0 mg/dL.
- Adequate renal function, as defined by a serum creatinine <1.5 mg/dL or a creatinine clearance or radioisotope GFR of > 60 mL/minute/1.73 m².
- Progressive disease at the time of inclusion into the study.
- ADA positivity due to previous treatment with an anti-GD2 antibody (e.g. ch14.18/SP2/0, ch14.18/CHO).
- Previous treatment with ch14.18/CHO in this study.
e) Requirement, or likely requirement, for corticosteroids or other immunosuppressive drugs.
f) Concurrent treatment with any non-trial anticancer therapies. g) Patients with hypersensitivity against one component of the investigational product or against mouse proteins.
h) Female patients of childbearing potential if 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.
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): NCT02743429
|St. Anna Kinderkrebsforschung e.V. CHILDREN'S CANCER RESEARCH INSTITUTE|
|Wien, Austria, 1090|
|University Medicine Greifswald|
|Greifswald, Germany, 17475|
|Study Director:||Holger Lode, Professor||University Medicine Greifswald|
|Responsible Party:||University Medicine Greifswald|
|Other Study ID Numbers:||
2014-000588-42 ( EudraCT Number )
|First Posted:||April 19, 2016 Key Record Dates|
|Last Update Posted:||October 4, 2021|
|Last Verified:||October 2021|
long term infusion
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue