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

Information source: National Cancer Institute (NCI)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Disseminated Neuroblastoma; Localized Resectable Neuroblastoma; Localized Unresectable Neuroblastoma; Regional Neuroblastoma; Stage 4S Neuroblastoma

Intervention: aldesleukin (Biological); sargramostim (Biological); monoclonal antibody Ch14.18 (Biological); isotretinoin (Drug)

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: National Cancer Institute (NCI)

Official(s) and/or principal investigator(s):
Mehmet Ozkaynak, MD, Principal Investigator, Affiliation: Children's Oncology Group

Summary

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.

Clinical Details

Official title: 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

Study design: Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Percentage of Patients Who Experienced a Significant (CTC Grade 3-5) Nonhematologic Toxicity of Interest (Pain, Hypotension, Allergic Reactions, Capillary Leak Syndrome, or Fever).

Secondary outcome:

Event-free Survival

Overall Survival

Detailed description: 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.

Eligibility

Minimum age: N/A. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Locations and Contacts

Loma Linda University Medical Center, Loma Linda, California 92354, United States

Children's Hospital Los Angeles, Los Angeles, California 90027, United States

Childrens Hospital of Orange County, Orange, California 92868-3874, United States

Lucile Packard Children's Hospital Stanford University, Palo Alto, California 94304, United States

Rady Children's Hospital - San Diego, San Diego, California 92123, United States

University of California San Francisco Medical Center-Parnassus, San Francisco, California 94143, United States

Children's Hospital Colorado, Aurora, Colorado 80045, United States

Children's Healthcare of Atlanta - Egleston, Atlanta, Georgia 30322, United States

University of Chicago Comprehensive Cancer Center, Chicago, Illinois 60637-1470, United States

Indiana University Medical Center, Indianapolis, Indiana 46202, United States

Children's Hospital-Main Campus, New Orleans, Louisiana 70118, United States

Dana-Farber Cancer Institute, Boston, Massachusetts 02115, United States

C S Mott Children's Hospital, Ann Arbor, Michigan 48109, United States

Children's Hospitals and Clinics of Minnesota - Minneapolis, Minneapolis, Minnesota 55404, United States

The Childrens Mercy Hospital, Kansas City, Missouri 64108, United States

Washington University School of Medicine, Saint Louis, Missouri 63110, United States

Columbia University Medical Center, New York, New York 10032, United States

Ny Cancer%, Valhalla, New York 10595, United States

Duke University Medical Center, Durham, North Carolina 27710, United States

Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, United States

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States

St. Jude Children's Research Hospital, Memphis, Tennessee 38105, United States

Vanderbilt-Ingram Cancer Center, Nashville, Tennessee 37232, United States

University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States

Cook Children's Medical Center, Fort Worth, Texas 76104, United States

Baylor College of Medicine, Houston, Texas 77030, United States

Seattle Children's Hospital, Seattle, Washington 98105, United States

University of Wisconsin Hospital and Clinics, Madison, Wisconsin 53792, United States

Additional Information

Starting date: December 2009
Last updated: February 25, 2015

Page last updated: August 23, 2015

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