CH14.18 1021 Antibody and IL2 After Haplo SCT in Children With Relapsed Neuroblastoma

Neuroblastoma Recurrent Clinical Trial

Official title:

Phase II Feasability Study Using ch14.18/CHO Antibody and Subcutaneous Interleukin 2 After Haploidentical Stem Cell Transplantation in Children With Relapsed Neuroblastoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02258815
• Other study ID #: EudraCT:2009-015936-14
• Status: Completed
• Phase: Phase 2
• Start date: August 2010
• Est. completion date: December 2022

Study information

• Verified date: December 2023
• Source: University Children's Hospital Tuebingen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A six courses regimen consisting of a 8 hour infusion (ch14.18/CHOmAb 20 mg/m²) for five consecutive days will be administered every 4 weeks, starting 60-180 days after previous haploidentical stem cell transplantation.

Interleukin 2 will be added to cycles 4-6 at days 6,8,10 (1 x 106 IU/m²/d s.c.) Participants will be premedicated with an intravenous antihistamine and ranitidine within approximately 30 minutes prior and during the infusion of the study agent Pain as an anticipated side effect is managed by a standard pain prophylaxis with Morphium hydrochloride Disease status will be evaluated after 3 and 6 courses and after 1 year

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: December 2022
• Est. primary completion date: November 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 21 Years

Eligibility

Inclusion Criteria:

• Less than or equal to 21 years of age.

• Histologically confirmed neuroblastoma.

• Refractory to standard treatment (i.e. refractory disease) or relapse after previous autologous or allogenic stem cell transplantation.

• Patient has undergone haploidentical stem cell transplantation prior to antibody infusion according to appendix IV at least 60 days prior to starting immunotherapy.

• Serum glutamate pyruvate transaminase (SGPT) less than 2.5 times the upper limit of normal for age and total bilirubin less than 2 times the upper limit of normal for age. D-Dimers less than 2 times the upper limit of normal.

Creatinine clearance or radioisotope GFR greater than or equal to 40 ml/min/1.73m2.

• Cardiac shortening fraction greater than or equal to 20% by echocardiogram. Karnofsky/Lansky performance score (age appropriate) of greater than or equal to 50.

• 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.

• Written informed consent is obtained, and for minors a written agreement by parents or legal guardian.

Exclusion Criteria:

• Marked baseline prolongation of QT/QTc interval (e.g. demonstration of a QTc interval > 450 milliseconds).

• 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 or active peptic ulcer, unless these conditions are corrected or controlled.

• Patients with acute GvHD Grade III or IV or extensive chronic GvHD.

• Patients with clinically significant, symptomatic, pleural effusions.

• Patients who have had major surgery, (i.e. laparotomy or thoracotomy) within the past two weeks.

• Patients who will more than 12 months post haploidentical stem cell transplantation at the time of starting the first cycle of immunotherapy.

• Prior administration of ch14.18 antibody after allogeneic stem cell transplantation (prior administration after autologous transplantation will be acceptable)

• HIV or Hepatitis B Surface (HBS) Ag positive. As presence of either may influence the ability if the immune system to be stimulated by this treatment.

Related Conditions & MeSH terms

• Neuroblastoma
• Neuroblastoma Recurrent

Intervention

Drug:
• ch14.18/CHO
A six courses regimen consisting of a 8 hour infusion (ch14.18/CHOmAb 20 mg/m² ) for five consecutive days will be administered every 4 weeks. Interleukin 2 will be added to cycles 4-6 at days 6,8,10 (1 x 106 IU/m²/d s.c.) Participants will be premedicated with an intravenous antihistamine and ranitidine within approximately 30 minutes prior and during the infusion of the study agent Pain as an anticipated side effect is managed by a standard pain prophylaxis with Morphium hydrochloride Disease status will be evaluated after 3 and 6 courses and after 1 year.

Locations

Country	Name	City	State
Austria	University Hospital Graz	Graz
Austria	St. Anna Childrens Hospital	Vienna
Germany	University Hospital Greifswald	Greifswald
Germany	University Hospital Tuebingen	Tuebingen

Sponsors (1)

Lead Sponsor	Collaborator
University Children's Hospital Tuebingen

Countries where clinical trial is conducted

Austria,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Success of treatment	Primary endpoint is "success of treatment" defined as a patient receiving the full protocol treatment, still alive 180 days after treatment without progression and without unacceptable toxicity and acute GvHD >= Grade III or extensive chronic GvHD.; Thus, a composite variable is used as primary endpoint: Treatment success, is defined as a patients who did not experience; unacceptable toxicities; acute GvHD >= Grade III or extensive chronic GvHD; other toxicities that did not recover to <= Grade 1 within 4 weeks or; progressive disease after 6 cycles or; deaths within treatment after SCT; withdrawal due to other reasons	180 days
Secondary	Anti tumour responses	• To evaluate the anti-tumour responses resulting from this immunotherapy regimen through clinical assessments (radiographic and clinical measurements, including bone marrow immunohistochemistry for those research participants with marrow involvement).	1 year
Secondary	Pharmakoinetics	* To evaluate pharmacokinetics of the ch14.18/CHO including analysis of cytokine levels in patients blood during administration. Antibody levels will be evaluated in determined intervals during Therapy	1 Year
Secondary	NK Cell aktivation and proliferation	* To evaluate changes in NK cell activation and proliferation (immunological monitoring) for additional support of potential Anti-tumor effect.	1 Year