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

Dermatologic Agents

Carboplatin

Antibodies

Antibodies, Monoclonal

Etoposide

Cyclophosphamide

Vincristine

Melphalan

Lenograstim

Etoposide phosphate

Immunoglobulins

Busulfan

Isotretinoin

Dinutuximab

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Enzyme Inhibitors

Tubulin Modulators

Antimitotic Agents

filgrastim

monoclonal antibody Ch14.18

busulfan

carboplatin

cyclophosphamide

etoposide

isotretinoin

melphalan

vincristine sulfate

bone marrow ablation with stem cell support

conventional surgery

peripheral blood stem cell transplantation

radiation therapy

Ruth Ladenstein, MD

Genevieve Laureys, MD, PhD

Henrik Schroder, MD

D. Valteau-Couanet

Fin Breatnach, MD, FRCPE

Isaac Yaniv, MD

Roberto Luksch, MD

Ingebjorg Storm-Mathisen, MD

Ana Forjaz De Lacerda, MD, FAAP

Victoria Castel

Per Kogner, MD, PhD

Maja B. Popovic, MD

Martin W. English, MD

Pamela Kearns, MD

Amos Burke, MD

Adam Glaser, MD

Johann Visser, MD

Heather P. McDowell, MD

Ananth Shankar, MD

Penelope Brock, MD, PhD

Bernadette Brennan, MD

Juliet Hale, MD

Martin Hewitt, MD, BSc, FRCP, FRCPCH

Kate Wheeler, MD

Mary P. Gerrard, MBChB, FRCP, FRCPCH

Janice A. Kohler, MD, FRCP

Mary Taj, MD

Anthony McCarthy, MD

Veronica Neefjes

W. Hamish Wallace, MD

Milind D. Ronghe, MD

Heidi Traunecker, MD, PhD

RATIONALE: Colony-stimulating factors such as filgrastim may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy. Combining chemotherapy with peripheral stem cell transplant may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining isotretinoin and monoclonal antibodies may kill any remaining tumor cells following surgery. It is not yet known which treatment regimen is more effective in treating neuroblastoma.

PURPOSE: This randomized phase III trial is studying how well combination chemotherapy with or without filgrastim before surgery, high-dose chemotherapy, and radiation therapy followed by isotretinoin with or without monoclonal antibody work in treating patients with neuroblastoma.

OBJECTIVES:

* Compare the efficacy of myeloablative therapy with busulfan and melphalan vs carboplatin, etoposide, and melphalan, in terms of 3- and 5-year event-free survival (EFS), progression-free survival (PFS), and overall survival (OS), in patients with high-risk neuroblastoma.
* Compare the 3-year EFS in these patients treated with isotretinoin with or without monoclonal antibody Ch14.18 after myeloablative therapy.
* Determine the response at metastatic sites after induction chemotherapy in these patients.
* Determine the effect of metastatic disease response after induction chemotherapy on EFS, PFS, and OS in these patients.
* Compare the toxicity and episodes of febrile neutropenia in patients treated with induction chemotherapy with or without filgrastim (G-CSF).
* Determine the effect of elective hematopoietic support with G-CSF during induction chemotherapy on peripheral blood stem cell collection in these patients.
* Compare the acute and long-term toxic effects of the 2 myeloablative therapy regimens in these patients.
* Determine the effect of radiotherapy on pre-surgical tumor volume at the primary site on local control, EFS, PFS, and OS in these patients.
* Determine the tolerability of isotretinoin with or without monoclonal antibody Ch14.18 after myeloablative therapy in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to disease stage (2 or 3 with MycN amplification vs 4). Patients are randomized to 1 of 8 treatment arms:

Arm I:

* Patients receive induction chemotherapy comprising vincristine IV, carboplatin IV over 1 hour, and etoposide IV over 4 hours on days 1 and 41; vincristine IV and cisplatin IV over 24 hours on days 11, 31, 51, and 71; and vincristine IV on days 21 and 61 and cyclophosphamide IV and etoposide over 4 hours on days 21, 22, 61, and 62. Patients receive filgrastim (G-CSF) subcutaneously on days 3-8, 12-18, 23-28, 32-38, 43-48, 52-58, 63-68, and 72 until peripheral blood stem cell (PBSC) collection.
* Patients undergo PBSC collection beginning on day 80. Patients then undergo surgery on day 95.
* Patients receive myeloablative therapy comprising oral busulfan 4 times daily on days -6 to -3 and melphalan IV over 15 minutes on day -2. Patients undergo PBSC infusion on day 0.
* Patients undergo radiotherapy in 14 fractions over 21 days.
* Beginning within 30 days after radiotherapy, patients receive oral isotretinoin twice daily on days 1-14. Treatment repeats every 28 days for 6 courses.

Arm II:

* Patients receive induction chemotherapy as in arm I, but with no G-CSF. Patients then undergo PBSC collection and surgery as in arm I. Patients receive myeloablative therapy and undergo PBSC infusion as in arm I. Patients undergo radiotherapy as in arm I.
* Patients receive oral isotretinoin twice daily on days 1-14 and monoclonal antibody Ch14.18 IV over 8 hours on days 1-5. Treatment repeats every 28 days for 6 courses for isotretinoin and every 28 days for 5 courses for monoclonal antibody Ch14.18.

Arm III:

* Patients receive induction chemotherapy and G-CSF as in arm I. Patients then undergo PBSC collection and surgery as in arm I. Patients receive myeloablative therapy and undergo PBSC infusion as in arm I. Patients undergo radiotherapy as in arm I. Patients receive isotretinoin as in arm I.

Arm IV:

* Patients receive induction chemotherapy as in arm II. Patients then undergo PBSC collection and surgery as in arm I. Patients receive myeloablative therapy and undergo PBSC infusion as in arm I. Patients undergo radiotherapy as in arm I. Patients receive isotretinoin and monoclonal antibody Ch14.18 as in arm II.

Arm V:

* Patients receive induction chemotherapy and G-CSF as in arm I.
* Patients receive myeloablative therapy comprising carboplatin IV continuously and etoposide IV continuously on days -7 to -4 and melphalan IV over 15 minutes on days -7 to -5. Patients undergo PBSC infusion on day 0.
* Patients undergo radiotherapy as in arm I. Patients receive isotretinoin as in arm I.

Arm VI:

* Patients receive induction chemotherapy as in arm II. Patients receive myeloablative therapy and undergo PBSC infusion as in arm V. Patients undergo radiotherapy as in arm I. Patients receive isotretinoin and monoclonal antibody Ch14.18 as in arm II.

Arm VII:

* Patients receive induction chemotherapy and G-CSF as in arm I. Patients receive myeloablative therapy and undergo PBSC infusion as in arm V. Patients undergo radiotherapy as in arm I. Patients receive isotretinoin as in arm I.

Arm VIII:

* Patients receive induction chemotherapy as in arm II. Patients receive myeloablative therapy and undergo PBSC infusion as in arm V. Patients undergo radiotherapy as in arm I. Patients receive isotretinoin and monoclonal antibody Ch14.18 as in arm II.

Patients on all treatment arms are followed every 6 months for 3 years and then annually for 2 years.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: Approximately 175 patients per year will be accrued for this study.

Combination Chemotherapy With or Without Filgrastim Before Surgery, High-Dose Chemotherapy, and Radiation Therapy Followed by Isotretinoin With or Without Monoclonal Antibody in Treating Patients With Neuroblastoma

High Risk Neuroblastoma Study 1 Of Siop-Europe

University of Leicester

Symptoms and General Pathology

Recurrence

Gaucher Disease Type 2

Anti-Infective Agents

Analgesics

Molgramostim

Sargramostim

Aldesleukin

Carbamide Peroxide

Interleukin-2

Analgesics, Non-Narcotic

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

Patients receive MOAB IV over 5 hours on days 7-10 during courses 2 and 4 and on days 3-6 during courses 1, 3, and 5; sargramostim (GM-CSF) IV over 2 hours or subcutaneously daily on days 0-13 during courses 1, 3, and 5; interleukin-2 IV continuously on days 0-3 and 7-10 during courses 2 and 4; and oral isotretinoin twice daily on days 14-27 during courses 2 and 4 and on days 10-23 during courses 3 and 5. Treatment repeats every 24-32 days for 5 courses in the absence of unacceptable toxicity.

aldesleukin

sargramostim

Andrew Gilman

Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Colony-stimulating factors such as sargramostim may increase the number of immune cells found in bone marrow or peripheral blood. Interleukin-2 may stimulate a person's white blood cells to kill cancer cells. Combining monoclonal antibody therapy with sargramostim or interleukin-2 may kill more tumor cells. Phase I trial to study the effectiveness of monoclonal antibody therapy given with sargramostim and interleukin-2 in treating children with neuroblastoma who have just completed bone marrow or peripheral stem cell transplantation

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose of monoclonal antibody (MOAB) ch14.18 when combined with sargramostim (GM-CSF) and interleukin-2 (IL-2) after autologous bone marrow or peripheral blood stem cell rescue in children with neuroblastoma.

II. Determine the toxic effects of this regimen in these patients. III. Determine the pharmacokinetics, including antibody level, antibody-binding activity, and presence of human anti-chimeric antibodies, of this regimen in these patients.

IV. Determine the activity of IL-2 and MOAB ch14.18 against tumor cells in terms of response using standard clinical measurements such as bone marrow immunocytology in these patients.

V. Determine the extent of coating of tumor cells (bone marrow metastases) by MOAB ch14.18 in these patients.

VI. Determine the feasibility of isotretinoin administered between courses beginning after course 2 in these patients.

OUTLINE: This is a multicenter, dose-escalation study of monoclonal antibody (MOAB).

Patients receive MOAB IV over 5 hours on days 7-10 during courses 2 and 4 and on days 3-6 during courses 1, 3, and 5; sargramostim (GM-CSF) IV over 2 hours or subcutaneously daily on days 0-13 during courses 1, 3, and 5; interleukin-2 IV continuously on days 0-3 and 7-10 during courses 2 and 4; and oral isotretinoin twice daily on days 14-27 during courses 2 and 4 and on days 10-23 during courses 3 and 5. Treatment repeats every 24-32 days for 5 courses in the absence of unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of MOAB until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. A minimum of 6 additional patients are treated at the MTD.

Patients are followed every other week for 2 months and then every 3 months for 6 months.

PROJECTED ACCRUAL: Approximately 6-16 patients will be accrued for this study within 1 year.

Monoclonal Antibody Therapy With Sargramostim and Interleukin-2 in Treating Children With Neuroblastoma

A PHASE I STUDY OF CHIMERIC HUMAN/MURINE ANTI-GD2 MONOCLONAL ANTIBODY (ch14.18) WITH GM-CSF AND INTERLEUKIN-2 (IL-2) IN CHILDREN WITH NEUROBLASTOMA IMMEDIATELY POST AUTOLOGOUS BMT OR PBSC RESCUE

National Cancer Institute (NCI)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Combination Chemotherapy With or Without Filgrastim Before Surgery, High-Dose Chemotherapy, and Radiation Therapy Followed by Isotretinoin With or Without Monoclonal Antibody in Treating Patients With Neuroblastoma	NCT00030719	Neuroblastoma	filgrastim monoclonal anti... busulfan carboplatin cyclophosphamid... etoposide isotretinoin melphalan vincristine sul... bone marrow abl... conventional su... peripheral bloo... radiation thera...	1 Year - 20 Years	National Cancer Institute (NCI)
Combination Chemotherapy With or Without Filgrastim Before Surgery, High-Dose Chemotherapy, and Radiation Therapy Followed by Isotretinoin With or Without Monoclonal Antibody in Treating Patients With Neuroblastoma	NCT00030719	Neuroblastoma	filgrastim monoclonal anti... busulfan carboplatin cyclophosphamid... etoposide isotretinoin melphalan vincristine sul... bone marrow abl... conventional su... peripheral bloo... radiation thera...	1 Year - 20 Years	National Cancer Institute (NCI)
Monoclonal Antibody Therapy With Sargramostim and Interleukin-2 in Treating Children With Neuroblastoma	NCT00005576	Disseminated Ne... Recurrent Neuro... Regional Neurob...	monoclonal anti... isotretinoin aldesleukin sargramostim	- 21 Years	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for monoclonal antibody ch14.18