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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00026312




Registration number
NCT00026312
Ethics application status
Date submitted
9/11/2001
Date registered
27/01/2003
Date last updated
10/05/2017

Titles & IDs
Public title
Isotretinoin With or Without Dinutuximab, Aldesleukin, and Sargramostim Following Stem Cell Transplant in Treating Patients With Neuroblastoma
Scientific title
Phase III Randomized Study of Chimeric Antibody 14.18 (Ch14.18) in High Risk Neuroblastoma Following Myeloablative Therapy and Autologous Stem Cell Rescue
Secondary ID [1] 0 0
NCI-2009-01064
Secondary ID [2] 0 0
NCI-2009-01064
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Localized Resectable Neuroblastoma 0 0
Localized Unresectable Neuroblastoma 0 0
Recurrent Neuroblastoma 0 0
Regional Neuroblastoma 0 0
Stage 4 Neuroblastoma 0 0
Stage 4S Neuroblastoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Cancer 0 0 0 0
Children's - Other

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Aldesleukin
Other interventions - Dinutuximab
Treatment: Drugs - Isotretinoin
Other interventions - Laboratory Biomarker Analysis
Other interventions - Pharmacological Study
Other interventions - Quality-of-Life Assessment
Other interventions - Sargramostim

Active Comparator: Arm I (isotretinoin) (closed to accrual as of 4/16/2009) - Beginning preferably between day 56 and day 85 post-ASCT, but may be delayed up to day 200, patients receive isotretinoin PO BID for 14 days. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients may cross over to Arm II provided they have not experienced disease progression and have not received any further anti-neuroblastoma therapy following completion of isotretinoin therapy.

Experimental: Arm II (sargramostim, dinutuximab, aldesleukin, isotretinoin) - Beginning preferably between day 56 and day 85 post-ASCT, but may be delayed up to day 200, patients receive immunotherapy comprising sargramostim SC or IV over 2 hours on days 0-13 during courses 1, 3, and 5 and dinutuximab IV over 10-20 hours on days 3-6 of courses 1-5. Patients also receive aldesleukin IV continuously on days 0-3 and 7-10 during courses 2 and 4. Immunotherapy repeats every 28 days for 5 courses in the absence of disease progression or unacceptable toxicity. Patients also receive isotretinoin as in Arm I beginning on day 11 of immunotherapy.


Other interventions: Aldesleukin
Given IV

Other interventions: Dinutuximab
Given IV

Treatment: Drugs: Isotretinoin
Given PO

Other interventions: Laboratory Biomarker Analysis
Correlative studies

Other interventions: Pharmacological Study
Correlative studies

Other interventions: Quality-of-Life Assessment
Ancillary studies

Other interventions: Sargramostim
Given IV or SC

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event-Free Survival (EFS) - Comparison to determine if RA + Immunotherapy improves EFS as compared to RA Only
Timepoint [1] 0 0
Three years
Secondary outcome [1] 0 0
Event-Free Survival (EFS) - Comparison to determine if RA + Immunotherapy improves EFS as compared to RA Only for the subgroup of randomized patients with INSS Stage 4 disease. Descriptive comparison of outcome data for patients with persistent disease documented by biopsy to historical data for the analogous patients from CCG-3981.
Timepoint [1] 0 0
Three years
Secondary outcome [2] 0 0
Event-Free Survival (EFS) of Patients From the Non-randomized Portion of the Trial - EFS for patients receiving RA + Immunotherapy following the cessation of the randomized portion of the study.
Timepoint [2] 0 0
Three years
Secondary outcome [3] 0 0
Incidence of Toxicities Assessed Using Common Terminology Criteria for Adverse Events Version 4.0 - Proportion of patients experiencing at least one Grade 3 or higher toxicity.
Timepoint [3] 0 0
From enrollment to follow-up
Secondary outcome [4] 0 0
Number of Courses of Therapy Delivered - Number of courses of therapy delivered for patients randomized to RA + Immunotherapy vs. patients non-randomly assigned to RA + Immunotherapy, excluding patients with persistent disease.
Timepoint [4] 0 0
Courses 1-6
Secondary outcome [5] 0 0
Overall Survival (OS) - Comparison to determine if RA + Immunotherapy improves OS as compared to RA Only. Comparison to determine if RA + Immunotherapy improves OS as compared to RA only and for the subgroup of randomized patients with INSS Stage 4 disease.
Timepoint [5] 0 0
Three years
Secondary outcome [6] 0 0
Overall Survival (OS) of Patients From the Non-randomized Portion of the Trial - OS for patients receiving RA + Immunotherapy following the cessation of the randomized portion of the study.
Timepoint [6] 0 0
Three years

Eligibility
Key inclusion criteria
- All patients must be diagnosed with neuroblastoma, and categorized as high risk at the
time of diagnosis; exception: patients who are initially diagnosed as non-high-risk
neuroblastoma, but later converted (and/or relapsed) to high risk neuroblastoma are
also eligible

- All patients must have completed therapy including intensive induction followed by
ASCT and radiotherapy to be eligible for ANBL0032; radiotherapy may be waived for
patients who either have small adrenal masses which are completely resected up front,
or who never have an identifiable primary tumor; examples of such therapies include:

- Following treatment per A3973 protocol

- Following treatment per Pediatric Oncology Group (POG)-9341/9342 protocol

- Following treatment per CCG3891

- Following treatment on New Approaches to Neuroblastoma Therapy (NANT) 2001-02

- Enrollment on or following treatment per ANBL02P1

- Enrollment on or following treatment per ANBL07P1

- Tandem transplant patients are eligible:

- Following treatment on or per ANBL0532

- Following treatment per POG 9640

- Following treatment per COG ANBL00P1

- Following treatment per CHP 594/Dana-Farber Cancer Institute (DFCI) 34-DAT

- No more than 12 months from the date of starting the first induction chemotherapy
after diagnosis to the date of ASCT except for the rare occasions as noted below; for
tandem ASCT patients, this will be the date of the FIRST stem cell infusion;
exception: for those who are initially diagnosed as non-high risk neuroblastoma, but
later converted (and/or relapsed) to high risk neuroblastoma, the 12 months
restriction should start from the date of induction therapy for high risk
neuroblastoma (not from the initial induction therapy for non-high risk disease), to
the date of ASCT

- At pre-ASCT evaluation patients must meet the International Neuroblastoma Response
Criteria (INRC) for CR, VGPR, or PR for primary site, soft tissue metastases and bone
metastases; patients who meet those criteria must also meet the protocol specified
criteria for bone marrow response as outlined below:

- =< 10% tumor (of total nucleated cellular content) seen on any specimen from a
bilateral bone marrow aspirate/biopsy

- Patient who have no tumor seen on the prior bone marrow, and then have =< 10%
tumor on any of the bilateral marrow aspirate/biopsy specimens done at pre-ASCT
and/or pre-enrollment evaluation will also be eligible (note that per INRC this
would have been defined as "overall" response of progressive disease [PD])

- Prior to enrollment on ANBL0032, a determination of mandatory disease staging must be
performed (tumor imaging studies including computed tomography [CT] or magnetic
resonance imaging [MRI], MIBG scan, and vanillylmandelic acid [VMA]/homovanillic acid
[HVA]; bone marrow aspirates are required but biopsy may be omitted if negative prior
to ASCT); this disease assessment is required for eligibility and should be done
preferably within 2 weeks, but must be done within a maximum of 4 weeks before
enrollment

- For those with residual disease before radiotherapy, re-evaluation of irradiated
residual tumors is preferably performed at the earliest 5 days after completing
radiotherapy; patients with residual disease are eligible; biopsy is not
required; patients who have biopsy proven residual disease after ASCT will be
enrolled on Stratum 07

- Patients must not have progressive disease at the time of study enrollment except
for protocol specified bone marrow response and except for elevations of
catecholamines as the only sign of disease in a patient who had normal
catecholamines at pre-ASCT evaluation

- Patients must be enrolled before treatment begins; the date protocol therapy is
projected to start must be no later than ten (10) calendar days after the date of
study enrollment; patients should be enrolled preferably between day 56 and day 85
after peripheral blood stem cell (PBSC) infusion (day from 2nd stem cell infusion for
tandem transplant); patients must be enrolled no later than day 200 after PBSC
infusion; enrollment must occur after completion of radiotherapy, and after completion
of tumor assessment post-ASCT and radiotherapy; informed consent should be obtained
within 3 weeks pre-ASCT up to the time of registration

- Patients must not have received prior anti-disialoganglioside (GD2) antibody therapy

- Patients must have a Lansky or Karnofsky performance scale score of >= 50% and
patients must have a life expectancy of >= 2 months

- Total absolute phagocyte count (APC = %neutrophils + %monocytes) X white blood cell
(WBC) is at least 1000/uL

- 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:

- No greater than 0.4 mg/dL (1 month to < 6 months)

- No greater than 0.5 mg/dL (6 months to < 1 year)

- No greater than 0.6 mg/dL (1 to < 2 years)

- No greater than 0.8 mg/dL (2 to < 6 years)

- No greater than 1.0 mg/dL (6 to < 10 years)

- No greater than 1.2 mg/dL (10 to < 13 years)

- No greater than 1.4 mg/dL (>= 13 years [female])

- No greater than 1.5 mg/dL (13 to < 16 years [male])

- No greater than 1.7 mg/dL (>= 16 years [male])

- Total bilirubin =< 1.5 x normal

- Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 5 x
normal

- Veno-occlusive disease, if present, should be stable or improving

- Shortening fraction of >= 27% by echocardiogram, or if shortening fraction abnormal,
ejection fraction of >= 55% by gated radionuclide study or echocardiogram; note: the
echocardiogram or gated radionuclide study must be performed within 4 weeks prior to
enrollment

- Forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) > 60%
predicted by pulmonary function test; for children who are unable to do pulmonary
function tests (PFTs), no evidence of dyspnea at rest and no exercise intolerance
should be documented; note: the pulmonary function test must be performed within 4
weeks prior to enrollment

- Patients with seizure disorder may be enrolled if on anticonvulsants and
well-controlled; central nervous system (CNS) toxicity < grade 2

- Written informed consent in accordance with institutional and Food and Drug
Administration (FDA) guidelines must be obtained from parent or legal guardian

- Females of childbearing potential must have a negative pregnancy test; patients of
childbearing potential must agree to use an effective birth control method; female
patients who are lactating must agree to stop breast-feeding
Minimum age
No limit
Maximum age
30 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
John Hunter Children's Hospital - Hunter Regional Mail Centre
Recruitment hospital [2] 0 0
Sydney Children's Hospital - Randwick
Recruitment hospital [3] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [4] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [5] 0 0
Lady Cilento Children's Hospital - South Brisbane
Recruitment hospital [6] 0 0
Women's and Children's Hospital-Adelaide - North Adelaide
Recruitment hospital [7] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [8] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
2310 - Hunter Regional Mail Centre
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
4029 - Herston
Recruitment postcode(s) [5] 0 0
4101 - South Brisbane
Recruitment postcode(s) [6] 0 0
5006 - North Adelaide
Recruitment postcode(s) [7] 0 0
3052 - Parkville
Recruitment postcode(s) [8] 0 0
6008 - Perth
Recruitment outside Australia
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United States of America
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Alabama
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United States of America
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Alaska
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United States of America
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Arizona
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Arkansas
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California
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Colorado
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Connecticut
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Delaware
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District of Columbia
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Florida
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Georgia
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Indiana
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Iowa
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Kentucky
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Utah
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Vermont
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Manitoba
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Newfoundland and Labrador
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Puerto Rico
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San Juan

Funding & Sponsors
Primary sponsor type
Government body
Name
National Cancer Institute (NCI)
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This partially randomized phase III trial studies isotretinoin with dinutuximab, aldesleukin,
and sargramostim to see how well it works compared to isotretinoin alone following stem cell
transplant in treating patients with neuroblastoma. Drugs used in chemotherapy, such as
isotretinoin, work in different ways to stop the growth of tumor cells, either by killing the
cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal
antibodies, such as dinutuximab, may block tumor growth in different ways by targeting
certain cells. Aldesleukin and sargramostim may stimulate a person's white blood cells to
kill cancer cells. It is not yet known if chemotherapy is more effective with or without
dinutuximab, aldesleukin, and sargramostim following stem cell transplant in treating
neuroblastoma.
Trial website
https://clinicaltrials.gov/show/NCT00026312
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Alice Yu
Address 0 0
Children's Oncology Group
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications