Trials / Completed

CompletedNCT01798004

Busulfan, Melphalan, and Stem Cell Transplant After Chemotherapy in Treating Patients With Newly Diagnosed High-Risk Neuroblastoma

Pilot Study Using Myeloablative Busulfan/Melphalan (BuMel) Consolidation Following Induction Chemotherapy for Patients With Newly Diagnosed High-Risk Neuroblastoma

Status: Completed
Phase: Phase 1
Study type: Interventional
Enrollment: 150 (actual)

Sponsor: Children's Oncology Group · Network
Sex: All
Age: 30 Years
Healthy volunteers: Not accepted

Summary

This pilot clinical trial studies busulfan, melphalan, and stem cell transplant after chemotherapy in treating patients with newly diagnosed neuroblastoma that is likely to come back or spread. Giving chemotherapy to the entire body before a stem cell transplant stops the growth of tumor cells by stopping them from dividing or killing them. After treatment, stem cells are collected from the patient's blood and stored. More chemotherapy or radiation therapy is given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy.

Detailed description

PRIMARY OBJECTIVES: I. To determine if the acute toxicity of an autologous stem cell transplant with a busulfan-melphalan (BuMel) based regimen is tolerable when given as consolidation therapy for high-risk neuroblastoma. EXPLORATORY OBJECTIVES: I. To determine the incidence of non-hematologic organ toxicity (grade 3 and higher) and all cause mortality in patients undergoing autologous stem cell transplant with a BuMel based regimen followed by local radiotherapy for the treatment of high-risk neuroblastoma. II. To describe response rates, event-free survival (EFS), and overall survival (OS) for patients undergoing induction therapy followed by consolidation with myeloablative BuMel preparative regimen and local radiotherapy for the treatment of high-risk neuroblastoma. III. To correlate busulfan pharmacokinetics with non-hematologic toxicity following a BuMel based autologous transplant regimen and event-free survival and overall survival. IV. To determine the feasibility of performing Curie scores in "real time," as assessed by central scan committee review of a 123 I-meta-iodobenzylguanidine (MIBG) scan obtained after cycle 4 of induction therapy. V. To examine the concordance between central reviewers and institutional reviewers in performing Curie scoring at diagnosis and after cycle 4 of induction therapy. VI. To determine the feasibility of detecting aberrations in the anaplastic lymphoma kinase (ALK) gene in tumors obtained at the time of diagnosis in patients with high-risk neuroblastoma. VII. To determine the feasibility of performing molecular profiling of neuroblastoma tumors obtained at the time of diagnosis in patients with high-risk neuroblastoma. VIII. To correlate melphalan pharmacokinetics with non-hematologic toxicity following a BuMel based autologous transplant regimen and event-free survival and overall survival. OUTLINE: INDUCTION THERAPY: COURSES 1-2: Patients receive cyclophosphamide intravenously (IV) over 15-30 minutes, topotecan hydrochloride IV over 30 minutes on days 1-5 and filgrastim subcutaneously (SC) or IV once daily (QD) beginning on day 6. Treatment repeats every 3 weeks for 2 courses. COURSES 3 AND 5: Patients receive cisplatin IV over 1 hour on days 1-4 and etoposide IV over 1-2 hours on days 1-3. Treatment repeats every 3 weeks for 2 courses. COURSE 4: Patients receive cyclophosphamide IV over 1-6 hours on days 1-2, vincristine sulfate IV over 1 minute on days 1-3, doxorubicin hydrochloride IV over 24 hours on days 1-3 and mesna IV over 15-30 minutes on days 1-2. Treatment repeats every 3 weeks for 1 course. Treatment continues in the absence of disease progression or unacceptable toxicity. CONSOLIDATION THERAPY: Beginning 4-8 weeks following the 5th course of induction therapy, patients receive busulfan IV over 3 hours on days -6 to -3 and melphalan IV on day -1. Patients undergo autologous stem cell transplant (ASCT) on day 0 and filgrastim SC or IV beginning on day 0. Some patients also undergo external beam radiation therapy (EBRT) after induction and consolidation. After completion of study treatment, patients are followed up every 3 months for 1 year, and then every 6 months for 4 years.

Conditions

Interventions

Type	Name	Description
PROCEDURE	Autologous Hematopoietic Stem Cell Transplantation	Undergo autologous peripheral blood stem cell transplant
DRUG	Busulfan	Given IV
DRUG	Cisplatin	Given IV
DRUG	Cyclophosphamide	Given IV
DRUG	Doxorubicin Hydrochloride	Given IV
DRUG	Etoposide	Given IV
RADIATION	External Beam Radiation Therapy	Undergo EBRT
BIOLOGICAL	Filgrastim	Given SC or IV
OTHER	Laboratory Biomarker Analysis	Optional correlative studies
DRUG	Melphalan	Given IV
DRUG	Mesna	Given IV
PROCEDURE	Peripheral Blood Stem Cell Transplantation	Undergo autologous peripheral blood stem cell transplant
OTHER	Pharmacological Study	Correlative studies
DRUG	Topotecan Hydrochloride	Given IV
DRUG	Vincristine Sulfate	Given IV

Timeline

Start date: 2013-04-09
Primary completion: 2015-07-28
Completion: 2024-06-30
First posted: 2013-02-25
Last updated: 2024-07-15
Results posted: 2017-02-09

Locations

123 sites across 4 countries: United States, Australia, Canada, New Zealand

Source: ClinicalTrials.gov record NCT01798004. Inclusion in this directory is not an endorsement.