Neoplasms

All Conditions

Rare Diseases

Neuroblastoma

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Micronutrients

Anti-Infective Agents

Fludarabine

Fludarabine phosphate

Rituximab

Melphalan

Immunomodulating Agents

Thiotepa

Iodine

Cadexomer iodine

3-Iodobenzylguanidine

Antineoplastic Agents, Immunological

Immunologic Factors

Immunosuppressive Agents

Antineoplastic Agents, Alkylating

Alkylating Agents

Enzyme Inhibitors

Radiopharmaceuticals

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

iodine I 131 metaiodobenzylguanidine

T-cell depletion

Haploidentical stem cell transplantation

Donor Lymphocyte Infusion

Co-transplantation of mesenchymal stem cells

Jacek Toporski, MD, PhD

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.

Haploidentical Stem Cell Transplantation in Neuroblastoma

High-dose MIBG With Subsequent Transplantation of Haploidentical Stem Cells in Children With Therapy Resistant Neuroblastoma

Lund University Hospital

MD, PhD

Symptoms and General Pathology

Recurrence

Topotecan

Topoisomerase I Inhibitors

topotecan hydrochloride

chemotherapy

peripheral blood stem cell transplantation

radioisotope therapy

radionuclide imaging

radiosensitization

total-body irradiation

Mark N. Gaze, MD

RATIONALE: Radioisotope therapy, such as iodine I 131 metaiodobenzylguanidine (MIBG), releases radiation that kills tumor cells. Drugs used in chemotherapy, such as topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Topotecan may also make tumor cells more sensitive to iodine I 131 MIBG. A peripheral stem cell transplant may be able to replace blood-forming cells that were destroyed by iodine I 131 MIBG and topotecan. This may allow more iodine I 131 MIBG and topotecan to be given so that more tumor cells are killed.

PURPOSE: This phase II trial is studying how well giving high-dose iodine I 131 MIBG together with topotecan and peripheral stem cell transplant works in treating young patients with relapsed stage 4 neuroblastoma or primary resistant high-risk neuroblastoma.

OBJECTIVES:

* Determine response (partial and complete response at metastatic sites) in children with relapsed stage 4 neuroblastoma or primary resistant high-risk neuroblastoma treated with high-dose iodine I 131 metaiodobenzylguanidine, topotecan hydrochloride, and peripheral blood stem cell transplantation.
* Determine the proportion of patients who, as a result of this treatment, are able to progress to potentially curative surgery and further systemic treatment.
* Correlate tumor dosimetry (to determine whether the tumor absorbed the radiation dose) with response in patients treated with this regimen.
* Determine the time to tumor progression.

OUTLINE: This is an open-label, multicenter study. Patients are stratified according to disease type (relapsed stage 4 vs primary resistant high-risk neuroblastoma).

Patients receive topotecan hydrochloride IV over 30 minutes on days 1-5 and 15-19 and high-dose iodine I 131 metaiodobenzylguanidine (\^131I-MIBG) IV over 30 minutes on days 1 and 15. Patients receive autologous CD 34+ peripheral blood stem cells when \^131I-MIBG dosimetry levels reach an acceptable low on days 25-29.

Total whole-body absorbed dose is measured periodically after the first \^131I-MIBG dose is administered and periodically thereafter.

After completion of study treatment, patients are followed periodically for up to 10 years.

PROJECTED ACCRUAL: A total of 67 patients will be accrued for this study.

High-Dose Iodine I 131 Metaiodobenzylguanidine, Topotecan, and Peripheral Stem Cell Transplant in Treating Young Patients With Relapsed Stage 4 Neuroblastoma or Primary Resistant High-Risk Neuroblastoma

International Phase II Studies of I-mIBG in Combination With Topotecan and Peripheral Blood Stem Cell Rescue for (A) Primary Resistant High Risk Neuroblastoma and (B) Relapsed Stage 4 Neuroblastoma

Children's Cancer and Leukaemia Group

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Haploidentical Stem Cell Transplantation in Neuroblastoma	NCT00790413	Neuroblastoma	iodine I 131 me... Fludarabine Thiotepa T-cell depletio... Haploidentical ... Donor Lymphocyt... Rituximab Co-transplantat...	6 Months - 21 Years	Lund University Hospital
High-Dose Iodine I 131 Metaiodobenzylguanidine, Topotecan, and Peripheral Stem Cell Transplant in Treating Young Patients With Relapsed Stage 4 Neuroblastoma or Primary Resistant High-Risk Neuroblastoma	NCT00389766	Neuroblastoma	iodine I 131 me... topotecan hydro... chemotherapy peripheral bloo... radioisotope th... radionuclide im... radiosensitizat... total-body irra...	1 Year - 17 Years	National Cancer Institute (NCI)
Haploidentical Stem Cell Transplantation in Neuroblastoma	NCT00790413	Neuroblastoma	iodine I 131 me... Fludarabine Thiotepa T-cell depletio... Haploidentical ... Donor Lymphocyt... Rituximab Co-transplantat...	6 Months - 21 Years	Lund University Hospital

Spots Global Cancer Trial Database for iodine i 131 metaiodobenzylguanidine