Haploidentical Stem Cell Transplantation in Neuroblastoma

NCT ID: NCT00790413

Last Updated: 2021-02-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

EARLY_PHASE1

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-08-31

Study Completion Date

2022-12-31

Brief Summary

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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.

Detailed Description

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Conditions

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Neuroblastoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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High-dose MIBG with haploidentical stem cell transplantation

High-dose MIBG followed by Fludarabine, Thiotepa and Melfalan as conditioning Before haploidentical transplantation of T-cell depleted graft

Group Type EXPERIMENTAL

iodine I 131 metaiodobenzylguanidine

Intervention Type DRUG

Fludarabine

Intervention Type DRUG

Thiotepa

Intervention Type DRUG

T-cell depletion

Intervention Type PROCEDURE

Haploidentical stem cell transplantation

Intervention Type PROCEDURE

Donor Lymphocyte Infusion

Intervention Type PROCEDURE

Rituximab

Intervention Type DRUG

Co-transplantation of mesenchymal stem cells

Intervention Type PROCEDURE

Interventions

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iodine I 131 metaiodobenzylguanidine

Intervention Type DRUG

Fludarabine

Intervention Type DRUG

Thiotepa

Intervention Type DRUG

T-cell depletion

Intervention Type PROCEDURE

Haploidentical stem cell transplantation

Intervention Type PROCEDURE

Donor Lymphocyte Infusion

Intervention Type PROCEDURE

Rituximab

Intervention Type DRUG

Co-transplantation of mesenchymal stem cells

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* Rapidly progressive disease
* Pregnancy
Minimum Eligible Age

6 Months

Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Lund University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Jacek Toporski

MD, PhD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jacek Toporski, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Lund University Hospital, Department of Pediatric Oncology

Locations

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Lund University Hospital, Department of Pediatric Oncology and Bone Marrow Transplantation

Lund, , Sweden

Site Status

Countries

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Sweden

References

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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.

Reference Type BACKGROUND
PMID: 12815485 (View on PubMed)

Matthay 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.

Reference Type BACKGROUND
PMID: 16421427 (View on PubMed)

Prigione 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.

Reference Type BACKGROUND
PMID: 15650233 (View on PubMed)

Neal 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.

Reference Type BACKGROUND
PMID: 14504825 (View on PubMed)

Raffaghello 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.

Reference Type BACKGROUND
PMID: 15897905 (View on PubMed)

Lang 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.

Reference Type BACKGROUND
PMID: 17080334 (View on PubMed)

Toporski 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.

Reference Type RESULT
PMID: 19660720 (View on PubMed)

Illhardt 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.

Reference Type RESULT
PMID: 29307718 (View on PubMed)

Other Identifiers

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385/2005

Identifier Type: -

Identifier Source: org_study_id

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