Back to resultsCH14.18 1021 Antibody and IL2 After Haplo SCT in Children With Relapsed Neuroblastoma
Primary Purpose
Neuroblastoma Recurrent
Status
Unknown status
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ch14.18/CHO
Sponsored by
About this trial
This is an interventional treatment trial for Neuroblastoma Recurrent focused on measuring pediatric, haploidentical, stem cell transplantation
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.
Sites / Locations
- University Hospital GrazRecruiting
- St. Anna Childrens HospitalRecruiting
- University Hospital GreifswaldRecruiting
- University Hospital TuebingenRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
ch14.18
Arm 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.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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).
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
NK Cell aktivation and proliferation
* To evaluate changes in NK cell activation and proliferation (immunological monitoring) for additional support of potential Anti-tumor effect.
Full Information
NCT ID
NCT02258815
First Posted
August 7, 2013
Last Updated
October 2, 2014
Sponsor
University Children's Hospital Tuebingen
1. Study Identification
Unique Protocol Identification Number
NCT02258815
Brief Title
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
2. Study Status
Record Verification Date
October 2014
Overall Recruitment Status
Unknown status
Study Start Date
August 2010 (undefined)
Primary Completion Date
December 2014 (Anticipated)
Study Completion Date
December 2015 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Children's Hospital Tuebingen
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroblastoma Recurrent
Keywords
pediatric, haploidentical, stem cell transplantation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
ch14.18
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
ch14.18/CHO
Other Intervention Name(s)
ch14.18, anti GD2 antibody
Intervention 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.
Primary Outcome Measure Information:
Title
Success of treatment
Description
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
Time Frame
180 days
Secondary Outcome Measure Information:
Title
Anti tumour responses
Description
• 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).
Time Frame
1 year
Title
Pharmakoinetics
Description
* 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
Time Frame
1 Year
Title
NK Cell aktivation and proliferation
Description
* To evaluate changes in NK cell activation and proliferation (immunological monitoring) for additional support of potential Anti-tumor effect.
Time Frame
1 Year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Peter Lang, MD, PhD
Phone
+4970712983781
Email
peter.lang@med.uni-tuebingen.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter Lang, MD, PhD
Organizational Affiliation
University Hospital Tuebingen
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital Graz
City
Graz
ZIP/Postal Code
8036
Country
Austria
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wolfgang Schwinger, MD, PhD
Phone
+43 31638512605
Email
wolfgang.schwinger@medunigraz.at
First Name & Middle Initial & Last Name & Degree
Wolfgang Schwinger, MD, PhD
Facility Name
St. Anna Childrens Hospital
City
Vienna
ZIP/Postal Code
1090
Country
Austria
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ruth Ladenstein, MD, PhD
Phone
43 1 40470 3250
Email
ruth.ladenstein@ccri.at
First Name & Middle Initial & Last Name & Degree
Ruth Ladenstein, MD, PhD
Facility Name
University Hospital Greifswald
City
Greifswald
ZIP/Postal Code
17475
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Holger Lode, MD, PhD
Phone
+49 3834866301
Email
lode@uni-greifswald.de
First Name & Middle Initial & Last Name & Degree
Holger Lode, MD, PhD
Facility Name
University Hospital Tuebingen
City
Tuebingen
ZIP/Postal Code
72076
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Peter Lang, MD, PhD
Phone
+4970712983781
Email
peter.lang@med.uni-tuebingen.de
First Name & Middle Initial & Last Name & Degree
Peter Lang, MD, PhD
12. IPD Sharing Statement
Citations:
PubMed Identifier
34367149
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.
Results Reference
derived
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CH14.18 1021 Antibody and IL2 After Haplo SCT in Children With Relapsed Neuroblastoma
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