|Phase III||Biomarker/Laboratory analysis, Treatment||Closed||Any age||NCI||NCI-2011-01997|
ANBL0931, U10CA098543, COG-ANBL0931, NCT01041638
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
Further Study Information
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.
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.
- 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
Trial Lead Organizations/Sponsors
National Cancer Institute
|Mehmet Ozkaynak||Principal Investigator|
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01041638
Information obtained from ClinicalTrials.gov on March 04, 2013
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