NeuroblastomaEarly Phase 1NCT00790413
Haploidentical Stem Cell Transplantation in Neuroblastoma
A Early Phase 1 study testing iodine I 131 metaiodobenzylguanidine, Fludarabine and Thiotepa in people with Neuroblastoma, run by Lund University Hospital at 1 site in Sweden.
Trial summary
Children with primary resistant or relapsed neuroblastoma who do not achieve remission with conventional chemotherapy have extremely dismal prognosis. A novel treatment strategy combining tumor targeted radioisotope treatment with metaiodobenzylguanidine (MIBG) and immunotherapeutic effect of haploidentical stem cell… Read more about this study
- Who is it for?
- Ages 6 months to 21 years
- Conditions the study is for
- Neuroblastoma
- What is being tested?
- iodine I 131 metaiodobenzylguanidine, Fludarabine and Thiotepa
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteSweden
- Study dates
- Aug 2005to 31 Dec 2022
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Refractory neuroblastoma (any chemo/radiosensitive stable disease)
- Relapse incl. autologous HSCT 3 m earlier
- Primary induction failure
- Cardiac output SF ≥25%
- Creatinine clearance ≥40 cc/min/1.73 m2
- Performance score of ≥50% (Lansky or Karnofsky)
- Available haploidentical family donor, aged ≥18 yrs, HIV-neg
Who cannot join
- Rapidly progressive disease
- Pregnancy
Trial locations and contacts
1 site in 1 country.
Sweden1 site
Lund University Hospital, Department of Pediatric Oncology and Bone Marrow Transplantation
Lund, 221 85
About this study
Official title: High-dose MIBG With Subsequent Transplantation of Haploidentical Stem Cells in Children With Therapy Resistant Neuroblastoma
Children with primary resistant or relapsed neuroblastoma who do not achieve remission with conventional chemotherapy have extremely dismal prognosis. A novel treatment strategy combining tumor targeted radioisotope treatment with metaiodobenzylguanidine (MIBG) and immunotherapeutic effect of haploidentical stem cell transplantation (haploSCT) followed by low-dose donor lymphocyte infusions will be piloted. The use of the isotope is aimed to decrease pre-transplant tumour burden. Reduced intensity conditioning containing Fludarabine, Thiotepa and Melfalan will enable sustained engraftment as well as will serve as additional anti-tumor treatment. A prompt natural killer (NK)-cell mediated tumour control may be achieved by haploidentical stem cell transplantation. The investigators hypothesize that tumour cells potentially evading NK-cell mediated immunity may be targeted by infused donor T-cells and eliminated by either MHC-dependent manner or through a bystander effect. The possible graft versus tumor effect will be evaluated in children with therapy resistant neuroblastoma.
- Conditions
- Neuroblastoma
- Being tested
- iodine I 131 metaiodobenzylguanidine, Fludarabine, Thiotepa, T-cell depletion, Haploidentical stem cell transplantation
- Keywords
- Radiotherapy, Immunotherapy, Hematopoietic Stem Cell Transplantation
- Medical subject headings
- Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
iodine I 131 metaiodobenzylguanidineDrug
FludarabineDrug
ThiotepaDrug
T-cell depletionProcedure or surgery
Haploidentical stem cell transplantationProcedure or surgery
Donor Lymphocyte InfusionProcedure or surgery
RituximabDrug
Co-transplantation of mesenchymal stem cellsProcedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| High-dose MIBG with haploidentical stem cell transplantation | Experimental | High-dose MIBG followed by Fludarabine, Thiotepa and Melfalan as conditioning Before haploidentical transplantation of T-cell depleted graft Receives: Drug: iodine I 131 metaiodobenzylguanidine; Drug: Fludarabine; Drug: Thiotepa; Procedure: T-cell depletion; Procedure: Haploidentical stem cell transplantation; Procedure: Donor Lymphocyte Infusion; Drug: Rituximab; Procedure: Co-transplantation of mesenchymal stem cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Engraftment rate
Measured: day 100
Secondary outcomes (3)
Overall survival
Measured: 1 year
Immunological reconstitution
Measured: day 100
Incidence of acute graft versus host disease
Measured: day 100
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2008 (estimated)
- Study startAug 2005
- Primary completion31 Dec 2022 (estimated)
- Study completion31 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for NeuroblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Lund University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jacek Toporski, Lund University Hospital
- Investigators
- Jacek Toporski, MD, PhD, Principal investigator, Lund University Hospital, Department of Pediatric Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00790413
- Sponsor's protocol ID
- 385/2005
- Status last verified
- Feb 2021
- First submitted
- 12 Nov 2008
- Last updated
- 21 Feb 2021
- Results posted
- No
Publications
Inoue M, Nakano T, Yoneda A, Nishikawa M, Nakayama M, Yumura-Yagi K, Sakata N, Yasui M, Okamura T, Kawa K. Graft-versus-tumor effect in a patient with advanced neuroblastoma who received HLA haplo-identical bone marrow transplantation. Bone Marrow Transplant. 2003 Jul;32(1):103-6. doi: 10.1038/sj.bmt.1704070.
PubMed 12815485Matthay KK, Tan JC, Villablanca JG, Yanik GA, Veatch J, Franc B, Twomey E, Horn B, Reynolds CP, Groshen S, Seeger RC, Maris JM. Phase I dose escalation of iodine-131-metaiodobenzylguanidine with myeloablative chemotherapy and autologous stem-cell transplantation in refractory neuroblastoma: a new approaches to Neuroblastoma Therapy Consortium Study. J Clin Oncol. 2006 Jan 20;24(3):500-6. doi: 10.1200/JCO.2005.03.6400.
PubMed 16421427Prigione I, Corrias MV, Airoldi I, Raffaghello L, Morandi F, Bocca P, Cocco C, Ferrone S, Pistoia V. Immunogenicity of human neuroblastoma. Ann N Y Acad Sci. 2004 Dec;1028:69-80. doi: 10.1196/annals.1322.008.
PubMed 15650233Neal ZC, Imboden M, Rakhmilevich AL, Kim KM, Hank JA, Surfus J, Dixon JR, Lode HN, Reisfeld RA, Gillies SD, Sondel PM. NXS2 murine neuroblastomas express increased levels of MHC class I antigens upon recurrence following NK-dependent immunotherapy. Cancer Immunol Immunother. 2004 Jan;53(1):41-52. doi: 10.1007/s00262-003-0435-2. Epub 2003 Sep 18.
PubMed 14504825Raffaghello L, Prigione I, Bocca P, Morandi F, Camoriano M, Gambini C, Wang X, Ferrone S, Pistoia V. Multiple defects of the antigen-processing machinery components in human neuroblastoma: immunotherapeutic implications. Oncogene. 2005 Jul 7;24(29):4634-44. doi: 10.1038/sj.onc.1208594.
PubMed 15897905Lang P, Pfeiffer M, Muller I, Schumm M, Ebinger M, Koscielniak E, Feuchtinger T, Foll J, Martin D, Handgretinger R. Haploidentical stem cell transplantation in patients with pediatric solid tumors: preliminary results of a pilot study and analysis of graft versus tumor effects. Klin Padiatr. 2006 Nov-Dec;218(6):321-6. doi: 10.1055/s-2006-942256.
PubMed 17080334Toporski J, Garkavij M, Tennvall J, Ora I, Gleisner KS, Dykes JH, Lenhoff S, Juliusson G, Scheding S, Turkiewicz D, Bekassy AN. High-dose iodine-131-metaiodobenzylguanidine with haploidentical stem cell transplantation and posttransplant immunotherapy in children with relapsed/refractory neuroblastoma. Biol Blood Marrow Transplant. 2009 Sep;15(9):1077-85. doi: 10.1016/j.bbmt.2009.05.007. Epub 2009 Jul 8.
PubMed 19660720Illhardt T, Toporski J, Feuchtinger T, Turkiewicz D, Teltschik HM, Ebinger M, Schwarze CP, Holzer U, Lode HN, Albert MH, Gruhn B, Urban C, Dykes JH, Teuffel O, Schumm M, Handgretinger R, Lang P. Haploidentical Stem Cell Transplantation for Refractory/Relapsed Neuroblastoma. Biol Blood Marrow Transplant. 2018 May;24(5):1005-1012. doi: 10.1016/j.bbmt.2017.12.805. Epub 2018 Jan 4.
PubMed 29307718
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- High-dose MIBG With Subsequent Transplantation of Haploidentical Stem Cells in Children With Therapy Resistant Neuroblastoma
- ClinicalTrials.gov ID
- NCT00790413
- Acronym / sponsor ID
- 385/2005
- Conditions
- Neuroblastoma
- Keywords
- Radiotherapy, Immunotherapy, Hematopoietic Stem Cell Transplantation
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Lund University HospitalUniversity, hospital or other
- Study start
- Aug 2005
- Primary completion
- 31 Dec 2022 (estimated)
- Study completion
- 31 Dec 2022 (estimated)
- First posted
- 13 Nov 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Children with primary resistant or relapsed neuroblastoma who do not achieve remission with conventional chemotherapy have extremely dismal prognosis. A novel treatment strategy combining tumor targeted radioisotope treatment with metaiodobenzylguanidine (MIBG) and immunotherapeutic effect of haploidentical stem cell transplantation (haploSCT) followed by low-dose donor lymphocyte infusions will be piloted. The use of the isotope is aimed to decrease pre-transplant tumour burden. Reduced intensity conditioning containing Fludarabine, Thiotepa and Melfalan will enable sustained engraftment as well as will serve as additional anti-tumor treatment. A prompt natural killer (NK)-cell mediated tumour control may be achieved by haploidentical stem cell transplantation. The investigators hypothesize that tumour cells potentially evading NK-cell mediated immunity may be targeted by infused donor T-cells and eliminated by either MHC-dependent manner or through a bystander effect. The possible graft versus tumor effect will be evaluated in children with therapy resistant neuroblastoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| High-dose MIBG with haploidentical stem cell transplantation | Experimental | Drug: iodine I 131 metaiodobenzylguanidine, Drug: Fludarabine, Drug: Thiotepa, Procedure: T-cell depletion, Procedure: Haploidentical stem cell transplantation, Procedure: Donor Lymphocyte Infusion, Drug: Rituximab, Procedure: Co-transplantation of mesenchymal stem cellsHigh-dose MIBG followed by Fludarabine, Thiotepa and Melfalan as conditioning Before haploidentical transplantation of T-cell depleted graft |
Who may qualify
- Ages
- 6 months to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- Refractory neuroblastoma (any chemo/radiosensitive stable disease)
- Relapse incl. autologous HSCT 3 m earlier
- Primary induction failure
- Cardiac output SF ≥25%
- Creatinine clearance ≥40 cc/min/1.73 m2
Key exclusion criteria (2 listed)
- Rapidly progressive disease
- Pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| iodine I 131 metaiodobenzylguanidine | Drug | High-dose MIBG with haploidentical stem cell transplantation |
| Fludarabine | Drug | High-dose MIBG with haploidentical stem cell transplantation |
| Thiotepa | Drug | High-dose MIBG with haploidentical stem cell transplantation |
| T-cell depletion | Procedure or surgery | High-dose MIBG with haploidentical stem cell transplantation |
| Haploidentical stem cell transplantation | Procedure or surgery | High-dose MIBG with haploidentical stem cell transplantation |
| Donor Lymphocyte Infusion | Procedure or surgery | High-dose MIBG with haploidentical stem cell transplantation |
| Rituximab | Drug | High-dose MIBG with haploidentical stem cell transplantation |
| Co-transplantation of mesenchymal stem cells | Procedure or surgery | High-dose MIBG with haploidentical stem cell transplantation |
Primary outcome
Engraftment rate
Time frame: day 100
3 secondary outcomes
Overall survival
Time frame: 1 year
Immunological reconstitution
Time frame: day 100
Incidence of acute graft versus host disease
Time frame: day 100
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2021.
- Background: PubMed 12815485Inoue M, Nakano T, Yoneda A, Nishikawa M, Nakayama M, Yumura-Yagi K, Sakata N, Yasui M, Okamura T, Kawa K. Graft-versus-tumor effect in a patient with advanced neuroblastoma who received HLA haplo-identical bone marrow transplantation. Bone Marrow Transplant. 2003 Jul;32(1):103-6. doi: 10.1038/sj.bmt.1704070.
- Background: PubMed 16421427Matthay KK, Tan JC, Villablanca JG, Yanik GA, Veatch J, Franc B, Twomey E, Horn B, Reynolds CP, Groshen S, Seeger RC, Maris JM. Phase I dose escalation of iodine-131-metaiodobenzylguanidine with myeloablative chemotherapy and autologous stem-cell transplantation in refractory neuroblastoma: a new approaches to Neuroblastoma Therapy Consortium Study. J Clin Oncol. 2006 Jan 20;24(3):500-6. doi: 10.1200/JCO.2005.03.6400.
- Background: PubMed 15650233Prigione I, Corrias MV, Airoldi I, Raffaghello L, Morandi F, Bocca P, Cocco C, Ferrone S, Pistoia V. Immunogenicity of human neuroblastoma. Ann N Y Acad Sci. 2004 Dec;1028:69-80. doi: 10.1196/annals.1322.008.
- Background: PubMed 14504825Neal ZC, Imboden M, Rakhmilevich AL, Kim KM, Hank JA, Surfus J, Dixon JR, Lode HN, Reisfeld RA, Gillies SD, Sondel PM. NXS2 murine neuroblastomas express increased levels of MHC class I antigens upon recurrence following NK-dependent immunotherapy. Cancer Immunol Immunother. 2004 Jan;53(1):41-52. doi: 10.1007/s00262-003-0435-2. Epub 2003 Sep 18.
- Background: PubMed 15897905Raffaghello L, Prigione I, Bocca P, Morandi F, Camoriano M, Gambini C, Wang X, Ferrone S, Pistoia V. Multiple defects of the antigen-processing machinery components in human neuroblastoma: immunotherapeutic implications. Oncogene. 2005 Jul 7;24(29):4634-44. doi: 10.1038/sj.onc.1208594.
- Background: PubMed 17080334Lang P, Pfeiffer M, Muller I, Schumm M, Ebinger M, Koscielniak E, Feuchtinger T, Foll J, Martin D, Handgretinger R. Haploidentical stem cell transplantation in patients with pediatric solid tumors: preliminary results of a pilot study and analysis of graft versus tumor effects. Klin Padiatr. 2006 Nov-Dec;218(6):321-6. doi: 10.1055/s-2006-942256.
- Results publication: PubMed 19660720Toporski J, Garkavij M, Tennvall J, Ora I, Gleisner KS, Dykes JH, Lenhoff S, Juliusson G, Scheding S, Turkiewicz D, Bekassy AN. High-dose iodine-131-metaiodobenzylguanidine with haploidentical stem cell transplantation and posttransplant immunotherapy in children with relapsed/refractory neuroblastoma. Biol Blood Marrow Transplant. 2009 Sep;15(9):1077-85. doi: 10.1016/j.bbmt.2009.05.007. Epub 2009 Jul 8.
- Results publication: PubMed 29307718Illhardt T, Toporski J, Feuchtinger T, Turkiewicz D, Teltschik HM, Ebinger M, Schwarze CP, Holzer U, Lode HN, Albert MH, Gruhn B, Urban C, Dykes JH, Teuffel O, Schumm M, Handgretinger R, Lang P. Haploidentical Stem Cell Transplantation for Refractory/Relapsed Neuroblastoma. Biol Blood Marrow Transplant. 2018 May;24(5):1005-1012. doi: 10.1016/j.bbmt.2017.12.805. Epub 2018 Jan 4.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jacek Toporski, MD, PhD principal investigator
Lund University Hospital, Department of Pediatric Oncology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing iodine I 131 metaiodobenzylguanidine, Fludarabine and Thiotepa in people with Neuroblastoma, run by Lund University Hospital at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 21 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Engraftment rate (time frame: day 100). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00790413, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2021.