Phase II Study of Monoclonal Antibody ch14.18/CHO Continuous Infusion in Patients With Primary Refractory or Relapsed Neuroblastoma

Neuroblastoma Clinical Trial

Official title:

Phase II Study of Monoclonal Antibody ch14.18/CHO Continuous Infusion in Patients With Primary Refractory or Relapsed Neuroblastoma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02743429
• Other study ID #: APN311-304
• Secondary ID: 2014-000588-42
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 27, 2015
• Est. completion date: June 2024

Study information

• Verified date: October 2021
• Source: University Medicine Greifswald
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In this trial, monoclonal anti-Disialoganglioside GD2 (GD2) antibody ch14.18/CHO will be assessed for the treatment of patients with relapsed or refractory neuroblastoma. The antibody is used as a single agent applied in a new treatment schedule associated with less side effects.

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: June 2024
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 21 Years

Eligibility

Inclusion Criteria:

1. = 12 months and = 21 years of age at the time of study entry

2. Diagnosis of neuroblastoma according to the INSS criteria

3. 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.

4. 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

5. Life expectancy of at least 12 weeks.

6. Performance status greater or equal to 70% (Lansky Score or Karnofsky)

7. Consent to the placement of a central venous line, if one has not already been placed

8. 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

9. No immediate requirements for palliative chemotherapy, radiotherapy or surgery

10. At least 2 weeks from any tumour surgery and fully recovered from any post-surgical complications

11. HIV sero-negative

12. Neither active nor chronic-replicative Hepatitis B infection

13. 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.

14. 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.

15. 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

16. All patients and/or their parents or legal guardians must sign a written informed consent.

17. Laboratory testing:

• 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.

Exclusion Criteria:

1. Progressive disease at the time of inclusion into the study.

2. ADA positivity due to previous treatment with an anti-GD2 antibody (e.g. ch14.18/SP2/0, ch14.18/CHO).

3. 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.

Related Conditions & MeSH terms

• Neuroblastoma

Intervention

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.

Locations

Country	Name	City	State
Austria	St. Anna Kinderkrebsforschung e.V. CHILDREN'S CANCER RESEARCH INSTITUTE	Wien
Germany	University Medicine Greifswald	Greifswald

Sponsors (2)

Lead Sponsor	Collaborator
University Medicine Greifswald	Children's Cancer Research Institute, Austria

Countries where clinical trial is conducted

Austria,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Anti-tumour activity of ch14.18/CHO continuous infusion	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.	2 years
Secondary	Progression-Free Survival		5 years
Secondary	Safety and tolerability	Pain intensity and the need for appropriate medication for pain relief; Adverse events, vital signs and changes in clinical laboratory assessments	2 years
Secondary	Immunogenicity	Immunogenicity: Anti-Drug Antibody (ADA)	2 years
Secondary	Immunophenotyping	Unit: cells/µl	2 years
Secondary	Antibody dependent cellular cytotoxicity (ADCC)	Unit: %	2 years
Secondary	Complement dependent cytotoxicity (CDC)	Unit: %	2 years
Secondary	Whole Blood Test (WBT)	Unit: %	2 years
Secondary	Cytokines	Unit: µg/ml	2 years
Secondary	Clearance (CL)	Unit: l/d*m²	2 years
Secondary	Volume distribution at steady state (Vdss)	Unit: l/m²	2 years
Secondary	mean residence time (MRT)	Unit: days	2 years
Secondary	half-life time (t1/2)	Unit: days	2 years
Secondary	Area Under the Curve (AUC)	Unit: µg*d/ml	2 years
Secondary	Maximum Plasma Concentration (Cmax) and Minimum Plasma Concentration (Cmin)	Unit: µg/ml	2 years