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

Eberhard Karls University of Tübingen

Status and phase: Completed; Phase 2

Conditions: Neuroblastoma Recurrent

Treatments: Drug: ch14.18/CHO

Study type: Interventional

Funder types: Other

Identifiers

NCT02258815

EudraCT:2009-015936-14

Details and patient eligibility

About

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

Enrollment: 35 estimated patients

Sex: All

Ages: 1 to 21 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

35 participants in 1 patient group

ch14.18

Experimental group

Description:

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.

Treatment:

Drug: ch14.18/CHO