Clinical trial NCT02258815: CH14.18 1021 Antibody and IL2 After Haplo SCT in Children With Relapsed Neuroblastoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neuroblastoma Recurrent
Keywords: pediatric
haploidentical
stem cell transplantation
Lead sponsor: University Children's Hospital Tuebingen
Sponsor class: OTHER
First posted: 2014-10-07
Enrollment: 35
Sex: ALL
Minimum age (years): 1
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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


Eligibility criteria: 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.

Primary outcomes:
measure: Success of treatment
timeFrame: 180 days
Secondary outcomes:
measure: Anti tumour responses
timeFrame: 1 year
measure: Pharmakoinetics
timeFrame: 1 Year
measure: NK Cell aktivation and proliferation
timeFrame: 1 Year
Other outcomes:
Locations:
city: Graz
country: Austria
facility: University Hospital Graz
city: Vienna
country: Austria
facility: St. Anna Childrens Hospital
city: Greifswald
country: Germany
facility: University Hospital Greifswald
city: Tuebingen
country: Germany
facility: University Hospital Tuebingen
Study officials:
affiliation: University Hospital Tuebingen
name: Peter Lang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Seitz CM, Flaadt T, Mezger M, Lang AM, Michaelis S, Katz M, Syring D, Joechner A, Rabsteyn A, Siebert N, Troschke-Meurer S, Zumpe M, Lode HN, Yang SF, Atar D, Mast AS, Scheuermann S, Heubach F, Handgretinger R, Lang P, Schlegel P. Immunomonitoring of Stage IV Relapsed Neuroblastoma Patients Undergoing Haploidentical Hematopoietic Stem Cell Transplantation and Subsequent GD2 (ch14.18/CHO) Antibody Treatment. Front Immunol. 2021 Jul 22;12:690467. doi: 10.3389/fimmu.2021.690467. eCollection 2021.