Monoclonal Antibody Ch14.18, Sargramostim, Aldesleukin, and Isotretinoin After Autologous Stem Cell Transplant in Treating Patients With Neuroblastoma

NCT ID: NCT01041638

Last Updated: 2021-08-17

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

105 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-12-21

Study Completion Date

2021-06-30

Brief Summary

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This phase III trial is studying the side effects of giving monoclonal antibody Ch14.18 together with sargramostim, aldesleukin, and isotretinoin after autologous stem cell transplant in treating patients with neuroblastoma. Monoclonal antibodies, such as Ch14.18, may find tumor cells and help kill them. Colony-stimulating factors, such as sargramostim, may increase the number of immune cells found in bone marrow or peripheral blood. Aldesleukin may stimulate the white blood cells to kill tumor cells. Isotretinoin may help neuroblastoma cells become more like normal cells, and to grow and spread more slowly. Giving monoclonal antibody Ch14.18 with sargramostim, aldesleukin, and isotretinoin after autologous stem cell transplant may be an effective treatment for neuroblastoma.

Detailed Description

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PRIMARY OBJECTIVES:

I. To comprehensively define the safety profile of ch14.18 when administered with cytokines and isotretinoin in high-risk neuroblastoma patients after autologous stem cell transplant (ASCT).

SECONDARY OBJECTIVES:

I. To further describe and refine the event-free survival (EFS) and overall survival (OS) estimates and baseline characteristics for subjects receiving chl4.18 + cytokines + isotretinoin.

II. To further describe the safety and toxicity of chl4.18 + cytokines + isotretinoin with focus on: a) number of courses delivered per patient; b) number of dose reductions or stoppage (ch14.18 and/or interleukin \[IL\]-2 \[aldesleukin\]); and c) number of toxic deaths.

III. To further describe the immune reconstitution of patients following ASCT, based on laboratory data obtained just prior to, during, and after treatment with this regimen.

IV. To obtain correlative laboratory data to evaluate and describe mechanisms related to response, toxicity of immune activation, and allergic phenomena.

OUTLINE:

Patients receive sargramostim subcutaneously (SC) or intravenously (IV) over 2 hours on days 0-13 of courses 1, 3, and 5; monoclonal antibody Ch14.18 IV over 10 hours on days 3-6 of courses 1, 3, and 5 and on days 7-10 of courses 2 and 4; and isotretinoin orally (PO) twice daily (BID) on days 11-24 of course 1, on days 14-27 of courses 2, 4, and 6, and on days 10-23 of courses 3 and 5. Patients also receive aldesleukin IV continuously on days 0-3 and on days 7-10 of courses 2 and 4. Treatment repeats every 24-32 days for 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up every 3 months for 1 year, every 6 months for 4 years, and then annually thereafter.

Conditions

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High Risk Neuroblastoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (Ch14.18, GM-CSF, IL-2, isotretinoin)

Patients receive sargramostim SC or IV over 2 hours on days 0-13 of courses 1, 3, and 5; monoclonal antibody Ch14.18 IV over 10 hours on days 3-6 of courses 1, 3, and 5 and on days 7-10 of courses 2 and 4; and isotretinoin PO BID on days 11-24 of course 1, on days 14-27 of courses 2, 4, and 6, and on days 10-23 of courses 3 and 5. Patients also receive aldesleukin IV continuously on days 0-3 and on days 7-10 of courses 2 and 4. Treatment repeats every 24-32 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Aldesleukin

Intervention Type BIOLOGICAL

Given IV

Diagnostic Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Dinutuximab

Intervention Type BIOLOGICAL

Given IV

Isotretinoin

Intervention Type DRUG

Given PO

Sargramostim

Intervention Type BIOLOGICAL

Given IV or SC

Interventions

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Aldesleukin

Given IV

Intervention Type BIOLOGICAL

Diagnostic Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Dinutuximab

Given IV

Intervention Type BIOLOGICAL

Isotretinoin

Given PO

Intervention Type DRUG

Sargramostim

Given IV or SC

Intervention Type BIOLOGICAL

Other Intervention Names

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125-L-Serine-2-133-interleukin 2 Proleukin r-serHuIL-2 Recombinant Human IL-2 Recombinant Human Interleukin-2 Ch 14.18UTC Ch14.18 MOAB Ch14.18 monoclonal antibody Ch14.18 Unituxin 13-cis retinoic acid 13-cis-Retinoate 13-cis-Retinoic Acid 13-cis-Vitamin A Acid 13-cRA Absorica Accure Accutane Amnesteem cis-Retinoic Acid Cistane Claravis Isotretinoinum Isotrex Isotrexin Myorisan Neovitamin A Neovitamin A Acid Oratane Retinoicacid-13-cis Ro 4-3780 Ro-4-3780 Roaccutan Roaccutane Roacutan Sotret ZENATANE 23-L-Leucinecolony-Stimulating Factor 2 DRG-0012 Leukine Prokine rhu GM-CFS Sagramostim Sargramostatin

Eligibility Criteria

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Inclusion Criteria

* All patients must be diagnosed with neuroblastoma, and categorized as high-risk at the time of diagnosis
* At pre-ASCT evaluation, patients must meet the International Neuroblastoma Response Criteria (INRC) for complete response (CR), very good partial response (VGPR), or partial response (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; patients 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 an "overall" response of progressive disease \[PD\])
* Prior to enrollment on ANBL0931, a determination of residual disease must be performed (tumor imaging studies including metaiodobenzylguanidine \[MIBG\] scan, computed tomography \[CT\] or magnetic resonance imaging \[MRI\], bone marrow aspiration and biopsy); 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

* Patients with residual disease are eligible; biopsy is not required
* Patients must not have progressive disease except for protocol specified bone marrow response
* All patients must have completed therapy including intensive induction chemotherapy followed by ASCT and radiotherapy to be eligible; radiotherapy may be waived for patients who either had a small adrenal mass which was completely resected upfront, or who never had an identifiable primary tumor
* No more than 9 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 9 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
* Use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age; required patients must have a Lansky or Karnofsky performance scale score of \>= 50%
* Patients must have a life expectancy of \>= 2 months (8 weeks)
* Total absolute phagocyte count (APC = neutrophils + monocytes) 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:

* 1 month to \< 6 months: 0.4 mg/dL
* 6 months to \< 1 year: 0.5 mg/dL
* 1 to \< 2 years: 0.6 mg/dL
* 2 to \< 6 years: 0.8 mg/dL
* 6 to \< 10 years: 1 mg/dL
* 10 to \< 13 years: 1.2 mg/dL
* 13 to \< 16 years: 1.5 mg/dL (male), 1.4 mg/dL (female)
* \>= 16 years: 1.7 mg/dL (male), 1.4 mg/dL (female)
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age
* Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) \< 5 x upper limit of normal (ULN) for age
* SOS (sinusoidal obstruction syndrome, formerly known as veno-occlusive disease \[VOD\]), if present, should be stable or improving
* Shortening fraction of \>= 27% by echocardiogram, or ejection fraction of \>= 55% by radionuclide angiography
* No evidence of dyspnea at rest
* If pulmonary function tests (PFTs) are performed, forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) \> 60% by pulmonary function test
* Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
* Central nervous system (CNS) toxicity \< grade 2

Exclusion Criteria

* 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
* Patients must not have received prior anti-GD2 antibody therapy
* Patients must not have received prior vaccine therapy administered as treatment of neuroblastoma not routine infectious disease vaccinations
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mehmet F Ozkaynak

Role: PRINCIPAL_INVESTIGATOR

Children's Oncology Group

Locations

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Loma Linda University Medical Center

Loma Linda, California, United States

Site Status

Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

Children's Hospital of Orange County

Orange, California, United States

Site Status

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, United States

Site Status

Rady Children's Hospital - San Diego

San Diego, California, United States

Site Status

UCSF Medical Center-Mount Zion

San Francisco, California, United States

Site Status

UCSF Medical Center-Parnassus

San Francisco, California, United States

Site Status

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status

Children's Healthcare of Atlanta - Egleston

Atlanta, Georgia, United States

Site Status

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, United States

Site Status

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Site Status

Indiana University/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Site Status

Riley Hospital for Children

Indianapolis, Indiana, United States

Site Status

Children's Hospital New Orleans

New Orleans, Louisiana, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

C S Mott Children's Hospital

Ann Arbor, Michigan, United States

Site Status

Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, United States

Site Status

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, United States

Site Status

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, United States

Site Status

New York Medical College

Valhalla, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Saint Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, United States

Site Status

Cook Children's Medical Center

Fort Worth, Texas, United States

Site Status

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, United States

Site Status

Seattle Children's Hospital

Seattle, Washington, United States

Site Status

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Site Status

Countries

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United States

Related Links

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https://nctn-data-archive.nci.nih.gov/

Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive.

Other Identifiers

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NCI-2011-01997

Identifier Type: REGISTRY

Identifier Source: secondary_id

COG-ANBL0931

Identifier Type: -

Identifier Source: secondary_id

ANBL0931

Identifier Type: -

Identifier Source: secondary_id

CDR0000662673

Identifier Type: -

Identifier Source: secondary_id

ANBL0931

Identifier Type: OTHER

Identifier Source: secondary_id

ANBL0931

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA098543

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2011-01997

Identifier Type: -

Identifier Source: org_study_id

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