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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01041638
First received: December 31, 2009
Last updated: March 14, 2016
Last verified: March 2016

December 31, 2009
March 14, 2016
December 2009
April 2014   (final data collection date for primary outcome measure)
Percentage of Patients Who Experienced a Significant (CTC Grade 3-5) Nonhematologic Toxicity of Interest (Pain, Hypotension, Allergic Reactions, Capillary Leak Syndrome, or Fever). [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
Designed to collect comprehensive safety/toxicity data, as well as additional efficacy data for the immunotherapy. To address the primary objective, descriptive analyses summarizing the number and type of AEs will be performed. The percentage of patients reporting each unacceptable (Grade 3 or higher) CTC toxicity code, tabulated by course, are reported.
Safety profile [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01041638 on ClinicalTrials.gov Archive Site
  • Event-free Survival [ Time Frame: From enrollment until the first occurrence of relapse, progressive disease, secondary malignancy, or death, or until last contact if no event occurred, up to 5 years ] [ Designated as safety issue: No ]
    Estimated using Kaplan-Meier curves.
  • Overall Survival [ Time Frame: From enrollment until death, or until last contact with the patient, up to 5 years ] [ Designated as safety issue: No ]
    Estimated using Kaplan-Meier curves.
  • Event-free Survival [ Designated as safety issue: No ]
  • Overall Survival [ Designated as safety issue: No ]
  • Immune reconstitution as assessed by T-cell recovery, NK-cell recovery, B-cell recovery, absolute neutrophil counts, monocyte counts, and absolute lymphocyte counts [ Designated as safety issue: No ]
  • In vivo immune activation by cytokine components as assessed by sIL2Rα serum levels and ch14.18 serum levels [ Designated as safety issue: No ]
  • Potential for allergic reactions as assessed by C3, C4, CH50, and c1q binding, tryptase, histamine levels, and total IgE [ Designated as safety issue: No ]
  • Genetic factors as assessed by FcR genotyping [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Monoclonal Antibody Ch14.18, Sargramostim, Aldesleukin, and Isotretinoin After Autologous Stem Cell Transplant in Treating Patients With Neuroblastoma
A Comprehensive Safety Trial of Chimeric Antibody 14.18 (Ch14.18) With GM-CSF, IL-2 and Isotretinoin in High-Risk Neuroblastoma Patients Following Myeloablative Therapy
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.

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.

Interventional
Phase 3
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Localized Resectable Neuroblastoma
  • Localized Unresectable Neuroblastoma
  • Regional Neuroblastoma
  • Stage 4 Neuroblastoma
  • Stage 4S Neuroblastoma
  • Biological: Aldesleukin
    Given IV
    Other Names:
    • 125-L-Serine-2-133-interleukin 2
    • Proleukin
    • r-serHuIL-2
    • Recombinant Human IL-2
    • Recombinant Human Interleukin-2
  • Other: Diagnostic Laboratory Biomarker Analysis
    Correlative studies
  • Biological: Dinutuximab
    Given IV
    Other Names:
    • Ch 14.18UTC
    • Ch14.18
    • MOAB Ch14.18
    • monoclonal antibody Ch14.18
    • Unituxin
  • Drug: Isotretinoin
    Given PO
    Other Names:
    • 13-cis retinoic acid
    • 13-cis-Retinoate
    • 13-cis-Retinoic Acid
    • 13-cis-Vitamin A Acid
    • 13-cRA
    • Accure
    • Accutane
    • Amnesteem
    • cis-Retinoic Acid
    • Cistane
    • Claravis
    • Isotretinoinum
    • Isotrex
    • Isotrexin
    • Neovitamin A
    • Neovitamin A Acid
    • Oratane
    • Retinoicacid-13-cis
    • Ro 4-3780
    • Ro-4-3780
    • Roaccutan
    • Roaccutane
    • Roacutan
    • Sotret
  • Biological: Sargramostim
    Given IV or SC
    Other Names:
    • 23-L-Leucinecolony-Stimulating Factor 2
    • DRG-0012
    • Leukine
    • Prokine
    • rhu GM-CFS
    • Sagramostim
    • Sargramostatin
Experimental: 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.
Interventions:
  • Biological: Aldesleukin
  • Other: Diagnostic Laboratory Biomarker Analysis
  • Biological: Dinutuximab
  • Drug: Isotretinoin
  • Biological: Sargramostim
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
105
Not Provided
April 2014   (final data collection date for primary outcome measure)

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
Both
Not Provided
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01041638
NCI-2011-01997, NCI-2011-01997, COG-ANBL0931, CDR0000662673, ANBL0931, ANBL0931, ANBL0931, U10CA098543
Not Provided
Not Provided
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Mehmet Ozkaynak Children's Oncology Group
National Cancer Institute (NCI)
March 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP