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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01041638
First received: December 31, 2009
Last updated: March 4, 2013
Last verified: March 2013

December 31, 2009
March 4, 2013
December 2009
December 2013   (final data collection date for primary outcome measure)
Number and type of adverse events assessed by Common Terminology Criteria for Adverse Events (CTCAE) [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
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, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to 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 together 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 monoclonal antibody Ch14.18 when administered with sargramostim, aldesleukin, and isotretinoin after autologous stem cell transplantation (ASCT) in patients with high-risk neuroblastoma.

SECONDARY OBJECTIVES:

I. To further describe and refine the event-free survival and overall survival estimates in patients treated with this regimen.

II. To further describe the baseline characteristics of patients treated with these regimen.

III. To further describe the safety and toxicity of this regimen, in terms of number of courses delivered per patient, number of dose reductions or stoppage, and number of toxic deaths, in these patients.

IV. To further describe the immune reconstitution following ASCT based on laboratory data obtained just before, during, and after treatment with this regimen.

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

OUTLINE: This is a multicenter study.

Patients receive sargramostim subcutaneously 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 oral isotretinoin twice daily 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.

Patients may undergo blood and bone marrow sample collection periodically for correlative laboratory studies.

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
  • Disseminated Neuroblastoma
  • Localized Resectable Neuroblastoma
  • Localized Unresectable Neuroblastoma
  • Regional Neuroblastoma
  • Stage 4S Neuroblastoma
  • Biological: aldesleukin
    Given IV
    Other Names:
    • IL-2
    • Proleukin
    • recombinant human interleukin-2
    • recombinant interleukin-2
  • Other: diagnostic laboratory biomarker analysis
    Correlative studies
  • Biological: sargramostim
    Given IV or SC
    Other Names:
    • GM-CSF
    • Leukine
    • Prokine
  • Biological: monoclonal antibody Ch14.18
    Given IV
    Other Names:
    • Ch14.18
    • MOAB Ch14.18
  • Drug: isotretinoin
    Given orally
    Other Names:
    • 13-CRA
    • Amnesteem
    • Cistane
    • Claravis
    • Sotret
Experimental: Arm I
Patients receive sargramostim subcutaneously 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 oral isotretinoin twice daily 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: sargramostim
  • Biological: monoclonal antibody Ch14.18
  • Drug: isotretinoin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
105
Not Provided
December 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Diagnosis of neuroblastoma

    • High risk at diagnosis
  • Meets the International Neuroblastoma Response Criteria (INRC) for complete response, very good partial response, or partial response for primary site, soft tissue metastasis, and bone metastasis AND meets the protocol-specified criteria for bone marrow response

    • No more than 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 a prior bone marrow aspirate/biopsy specimen and then have ≤ 10% tumor seen on any of the bilateral marrow aspirate/biopsy specimens done at pre-autologous stem cell transplantation (ASCT) and/or pre-study enrollment evaluation are eligible
  • Residual disease by MIBG scan, CT scan, MRI, bone marrow aspiration, or biopsy allowed
  • No progressive disease other than protocol-specified bone marrow response as described above
  • Must have completed therapy that included intensive induction chemotherapy followed by ASCT and radiotherapy within the past 100 days

    • Radiotherapy may be waived for patients who either had a small adrenal mass that was completely resected up-front or who never had an identifiable primary tumor
    • No more than 9 months between the date of starting the first induction chemotherapy after diagnosis to the date of ASCT (for patients who have undergone tandem ASCT, this is the date of the first stem cell infusion)

      • For patients who were 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
  • Lansky performance status (PS) 50-100% (for patients ≤ 16 years of age) OR Karnofsky PS 50-100% (for patients > 16 years of age)
  • Life expectancy ≥ 2 months
  • Absolute phagocyte count ≥ 1,000/μL
  • Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR maximum serum creatinine based on age/gender as follows:

    • 0.4 mg/dL (1 to 5 months of age)
    • 0.5 mg/dL (6 to 11 months of age)
    • 0.6 mg/dL (1 year of age)
    • 0.8 mg/dL (2 to 5 years of age)
    • 1.0 mg/dL (6 to 9 years of age)
    • 1.2 mg/dL (10 to 12 years of age)
    • 1.5 mg/dL (males) or 1.4 mg/dL (females) (13 to 15 years of age)
    • 1.7 mg/dL (males) or 1.4 mg/dL (females) (≥ 16 years of age)
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • ALT < 5 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Shortening fraction ≥ 27% by ECHO OR ejection fraction ≥ 55% by radionuclide angiography
  • FEV_1/FVC > 60% by pulmonary function test (if performed)
  • No evidence of dyspnea at rest
  • No CNS toxicity ≥ grade 2
  • Seizure disorder allowed provided patient is on anticonvulsants and it is well controlled
  • Sinusoidal obstruction syndrome allowed provided it is stable or improving
  • No other concurrent anticancer therapy
  • No prior anti-GD2 antibody therapy
  • No prior vaccine therapy for neuroblastoma
  • No concurrent pentoxifylline or immunosuppressive drugs (e.g., cyclosporine or corticosteroids [other than for the treatment of acute allergic reactions to immunotherapy or treatment of increased intracranial pressure in patients with CNS tumors])
  • No other concurrent cytokines or growth factors
Both
Not Provided
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01041638
NCI-2011-01997, ANBL0931, U10CA098543
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 2013

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