Pilot Study Using Myeloablative Busulfan/Melphalan (BuMel) Consolidation Following Induction Chemotherapy for Patients With Newly Diagnosed High-Risk Neuroblastoma
N/A
30 Years
Both
Neuroblastoma
Trial Information
Pilot Study Using Myeloablative Busulfan/Melphalan (BuMel) Consolidation Following Induction Chemotherapy for Patients With Newly Diagnosed High-Risk Neuroblastoma
This groupwide pilot study examines the toxicity profile of the Busulfan-Melphalan (BuMel)
myeloablative preparative regimen in children and young adults with newly diagnosed
high-risk neuroblastoma. The primary objective of the proposed study will be to examine the
toxicity profile of this regimen in the context of COG therapy, with specific focus on the
incidence and severity of pulmonary and hepatic toxicity. The Induction regimen will be 5
cycles of Induction. Consolidation therapy will consist of 4 doses of busulfan IV given once
daily followed by a single dose of melphalan with a rest day prior to and following the
melphalan dose. After recovery from Consolidation radiation therapy, patients will be
encouraged to participate in clinical trials of ch14.18 immunotherapy (ie, ANBL0032 or
other).
Additional examinations will include pharmacokinetic measurements of busulfan and melphalan
that will be collected and correlated with toxicity and survival. We will examine the
ability to perform Curie scoring in real time, within 21 days of scan acquisition. This will
be the first prospective use of Curie scoring in a cooperative group setting. This study
will examine our ability to perform ALK gene testing prospectively, within 4 to 6 weeks of
sample acquisition, by a centralized lab. Aberrations of the ALK gene in neuroblastoma
tumors have been reported by multiple investigators, with potential therapeutic
implications. Potential targeted inhibitors of ALK aberrations are now available, and may
impact future clinical trial designs. In addition, molecular profiling of MYCN non-amplified
tumors with a 14-gene signature panel will be performed. This study will test our ability to
obtain tumor samples prospectively and identify molecular profiles within 6-8 weeks of
sample acquisition which may also impact future clinical trial design.
Inclusion Criteria:
- Patients must have a diagnosis of neuroblastoma (International Classification of
Diseases for Oncology [ICD-O] morphology 9500/3) or ganglioneuroblastoma (nodular or
intermixed) verified by histology or demonstration of clumps of tumor cells in bone
marrow with elevated urinary catecholamine metabolites; patients with the following
disease stages at diagnosis are eligible, if they meet the other specified criteria
- Patients with newly diagnosed neuroblastoma with International Neuroblastoma Staging
System (INSS) stage 4 are eligible with the following:
- MYCN amplification (> 4-fold increase in MYCN signals as compared to reference
signals), regardless of age or additional biologic features
- Age > 18 months (> 547 days) regardless of biologic features
- Age 12-18 months (365-547 days) with any of the following 3 unfavorable biologic
features (MYCN amplification, unfavorable pathology and/or DNA index = 1) or any
biologic feature that is indeterminate/unsatisfactory/unknown
- Patients with newly diagnosed neuroblastoma with INSS stage 3 are eligible with the
following:
- MYCN amplification (> 4-fold increase in MYCN signals as compared to reference
signals), regardless of age or additional biologic features
- Age > 18 months (> 547 days) with unfavorable pathology, regardless of MYCN
status
- Patients with newly diagnosed neuroblastoma with INSS stage 2A/2B with MYCN
amplification (> 4-fold increase in MYCN signals as compared to reference signals),
regardless of age or additional biologic features
- Patients with newly diagnosed neuroblastoma with INSS Stage 4S with MYCN
amplification (> 4-fold increase in MYCN expression signals as compared to reference
signals), regardless of additional biologic features
- Patients >= 365 days initially diagnosed with neuroblastoma INSS stage 1, 2, 4S who
progressed to a stage 4 without interval chemotherapy; these patients must have been
enrolled on ANBL00B1; study enrollment on ANBL12P1 must occur within 4 weeks of
progression to stage 4 for INSS stage 1, 2, 4S
- Patients must not have had prior systemic therapy except for localized emergency
radiation to sites of life-threatening or function-threatening disease and/or no more
than 1 cycle of chemotherapy per a low or intermediate risk neuroblastoma regimen (as
per P9641, A3961, ANBL0531, or similar) prior to determination of MYCN amplification
status and histology
- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
- Age 1 month to < 6 months: 0.4 mg/dL
- Age 6 months to < 1 year: 0.5 mg/dL
- Age 1 to < 2 years: 0.6 mg/dL
- Age 2 to < 6 years: 0.8 mg/dL
- Age 6 to < 10 years: 1 mg/dL
- Age 10 to < 13 years: 1.2 mg/dL
- Age 13 to < 16 years: 1.5 mg/dL (males), 1.4 mg/dL (females)
- Age >= 16 years: 1.7 mg/dL (males), 1.4 mg/dL (females)
- Total bilirubin =< 1.5 x upper limit of normal (ULN) for age, and
- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or
serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 10 x
ULN for age
- Shortening fraction of >= 27% by echocardiogram, or ejection fraction of >= 50% by
radionuclide evaluation
- No known contraindication to peripheral blood stem cell (PBSC) collection; examples
of contraindications might be a weight or size less than that determined to be
feasible at the collecting institution, or a physical condition that would limit the
ability of the child to undergo apheresis catheter placement (if necessary) and/or
the apheresis procedure.
Exclusion Criteria:
- Patients that are 12-18 months of age with INSS stage 4 and all 3 favorable biologic
features (ie, nonamplified MYCN, favorable pathology, and DNA index > 1) are not
eligible
- Female patients who are pregnant are ineligible due to risks of fetal and teratogenic
adverse events
- Lactating females are not eligible unless they have agreed not to breastfeed their
infants
- Female patients of childbearing potential are not eligible unless a negative
pregnancy test result has been obtained
- Sexually active patients of reproductive potential are not eligible unless they have
agreed to use an effective contraceptive method for the duration of their study
participation.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Number of patients who experience one or more unacceptable toxicities (severe sinusoidal obstruction syndrome [SOS] or grade 4-5 pulmonary toxicity per Common Toxicity Criteria [CTC] v.4.0) during the consolidation phase of therapy
Outcome Description:
The primary study endpoint is the tolerability of the BuMel regimen, which will be quantified as the number of patients who experience one or more unacceptable toxicities (severe SOS (Sinusoidal obstruction syndrome) or Grade 4-5 pulmonary toxicity per CTCv.4.0) during the Consolidation phase of therapy.
Outcome Time Frame:
Up to 28 days post-consolidation therapy
Safety Issue:
Yes
Principal Investigator
Meaghan Granger, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Cook Children's Medical Center
Authority:
United States: Food and Drug Administration
Study ID:
ANBL12P1
NCT ID:
NCT01798004
Start Date:
April 2013
Completion Date:
Related Keywords:
- Neuroblastoma
- Newly diagnosed High Risk Neuroblastoma
- Disseminated neuroblastoma
- Localized resectable neuroblastoma
- Regional neuroblastoma
- Stage 4S neuroblastoma
- Neuroblastoma
Name | Location |
|---|---|
| Children's Oncology Group | Arcadia, California 91006-3776 |
