Biological Therapy, Sargramostim, and Isotretinoin in Treating Patients With Relapsed or Refractory Neuroblastoma

Completed · Phase 2

Conditions studied: Recurrent Neuroblastoma

In brief

This phase II trial is studying how well hu14.18-interleukin-2 (IL2) fusion protein works when given together with sargramostim and isotretinoin in treating patients with relapsed or refractory neuroblastoma. Biological therapy, such as hu14.18-IL2 fusion protein, and sargramostim work in different ways to stimulate the immune system and stop tumor cells from growing. Drugs used in chemotherapy, such as isotretinoin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving hu14.18-IL2 fusion protein together with sargramostim and isotretinoin may kill more tumor cells.

Key facts

Study ID

NCT01334515

Run by

Children's Oncology Group

People needed

52

Starts

2011-09-01

Expected to finish

2019-09-30

Last updated by the study team

2019-10-21

Who can join

Age: 1 and older, up to 30. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• The target tumor is limited to neuroblastoma; patients must have had histologic verification of neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines at the time of initial diagnosis
• Patients must have resistant/refractory or recurrent neuroblastoma
• Tumor imaging and bone marrow evaluation for histologic analysis of marrow tumor cell quantity must be obtained within 3 weeks (21 days) prior to enrollment onto study and patients must have one of the following:
• Measurable tumor on magnetic resonance imaging (MRI), computed tomography (CT) scan, or x-ray defined as minimum of 20 mm in at least one dimension; measurable is defined as minimum of 20 mm in at least one dimension; for patients who are in first response (i.e., those patients with persistent sites of tumor after frontline therapy, but who have never relapsed), a biopsy of a lesion or bone marrow must demonstrate viable neuroblastoma following completion of therapy; if the lesion was irradiated, the biopsy must be done at least 4 weeks after radiation is completed
• Meta iodo benzyl guanidine I 123 (MIBG) scan with positive uptake at minimum of one site; for patients in first response, a biopsy of site must demonstrate viable tumor; if lesion was radiated, biopsy must be done at least 4 weeks after radiation completed
• Bone marrow with tumor cells seen on routine morphology (not by neuron specific enolase (NSE) staining only) of bilateral aspirate and/or biopsy on one bone marrow sample
• Patients must have a performance status of 0, 1 or 2; use Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age
• Patients must have a life expectancy of ≥ 8 weeks
• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
• Myelosuppressive chemotherapy: Must not have received within 3 weeks of entry onto this study (4 weeks if prior nitrosourea).
• Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a non-myelosuppressive biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; for information on half-lives of these agents, refer to the table provided in the following link: https://members.childrensoncologygroup.org/_files/disc/dvl/Half-lifetableforeligibility.pdf
• External beam radiation therapy (XRT): >= 2 wks for local palliative XRT (small port); >= 6 months must have elapsed if prior craniospinal XRT or if >= 50% radiation of pelvis; >= 6 weeks must have elapsed if other substantial bone marrow (BM) radiation
• Autologous stem cell transplant (ASCT): Patients are eligible > 56 days after autologous stem cell infusion following myeloablative therapy; patients receiving an autologous stem cell infusion to support non-myeloablative therapy (including 131I-MIBG given as a single agent) are eligible at any time as long as they meet the hematologic and other organ function criteria for eligibility; patients who have received an allogenic stem cell transplant are excluded
• radioactive iodine (131 I) MIBG therapy: Patients are eligible > 6 weeks after therapeutic 131I-MIBG
• Study specific limitations on prior therapy: Subjects who have previously received in vivo anti-GD2 monoclonal antibodies for biologic therapy or for tumor imaging, are eligible unless they have had progressive disease or a severe allergic reaction while receiving prior anti-disialoganglioside (GD2) therapy; subjects who have received autologous marrow infusions or autologous stem cell infusions using monoclonal antibody linked to beads to purge specimens, but no other form of anti-GD2 monoclonal antibody, are eligible
• Growth factor(s): Must not have received within 1 week of entry onto this study
• Steroids: Patients who require or are likely to require corticosteroid or other immunosuppressive drugs for intercurrent disease (any other significant medical problem related to or independent from the neuroblastoma or its treatment) while tentatively scheduled to be receiving treatment on this study are ineligible; the only exception is for patients known to require 2 mg/kg or less of hydrocortisone (or an equivalent dose of an alternative corticosteroid) as premedication for blood product transfusion in order to avoid allergic transfusion reactions
• Peripheral absolute phagocyte count (APC=neutrophils + monocytes) >= 1000/uL
• Platelet count ≥ 20,000/μL*
• Hemoglobin ≥ 8 g/dL*
• Transfusions are permitted to meet these platelet and hemoglobin criteria, if the patient is known to have a history of bone marrow involvement with tumor; patients with platelet counts < 20,000/uL who are refractory to platelet transfusions are not eligible for this study; patients requiring transfusions of platelets or red blood cells (RBC) to meet eligibility criteria will not be evaluable for hematologic toxicity
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min OR serum creatinine based on age/gender as follows:
• 0.4 mg/dL (1 month to < 6 months of age)
• 0.5 mg/dL (6 months to < 1 years of age)
• 0.6 mg/dL (1 to < 2 years of age)

You may not qualify if…

• Females of childbearing potential must have a negative pregnancy test
• Patients of childbearing potential must agree to use an effective birth control method (as isotretinoin is known to be teratogenic)
• Female patients who are lactating must agree to stop breast-feeding
• Patients with symptoms of congestive heart failure or uncontrolled cardiac rhythm disturbance are not eligible
• Patients with symptomatic pleural effusions or ascites (requiring constant or intermittent drainage) because IL2 is associated with capillary leak are not eligible
• Patients who have had major surgery (i.e., laparotomy or thoracotomy) within the past 2 weeks are not eligible, due to the capillary leak associated with IL2
• Patients with organ allografts (including bone marrow or stem cell) due to the immune activating effects of IL2 are not eligible; patients receiving prior autologous bone marrow or stem cell re-infusions are eligible
• Patients with prior history of ventilator support related to lung injury (lung injury such as pneumonia, hemorrhagic pneumonitis, capillary leakage) are excluded
• Patients with significant serious intercurrent illnesses (any other ongoing serious medical problem unrelated to cancer or its treatment) that is not covered by the detailed exclusion criteria and which is expected to interfere with the action of hu14.18-IL2 or to significantly increase the severity of the toxicities experienced from hu14.18-IL2 treatment are not eligible

Where it is running

• University of Arkansas for Medical Sciences — Little Rock, Arkansas, United States
• Children's Oncology Group — Arcadia, California, United States
• Loma Linda University Medical Center — Loma Linda, California, United States
• Children's Hospital Los Angeles — Los Angeles, California, United States
• Children's Hospital Central California — Madera, California, United States
• Childrens Hospital of Orange County — Orange, California, United States
• Rady Children's Hospital - San Diego — San Diego, California, United States
• University of California San Francisco Medical Center-Parnassus — San Francisco, California, United States
• Children's Hospital Colorado — Aurora, Colorado, United States
• Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center — Denver, Colorado, United States
• Connecticut Children's Medical Center — Hartford, Connecticut, United States
• Children's National Medical Center — Washington D.C., District of Columbia, United States
• Lee Memorial Health System — Fort Myers, Florida, United States
• Nemours Children's Clinic - Jacksonville — Jacksonville, Florida, United States
• Miami Children's Hospital — Miami, Florida, United States
• Florida Hospital — Orlando, Florida, United States
• All Children's Hospital — St. Petersburg, Florida, United States
• Children's Healthcare of Atlanta - Egleston — Atlanta, Georgia, United States
• University of Hawaii — Honolulu, Hawaii, United States
• University of Illinois — Chicago, Illinois, United States
• University of Chicago Comprehensive Cancer Center — Chicago, Illinois, United States
• Southern Illinois University — Springfield, Illinois, United States
• Riley Hospital for Children — Indianapolis, Indiana, United States
• Raymond Blank Children's Hospital — Des Moines, Iowa, United States
• University of Alabama at Birmingham — Birmingham, Alabama, United States

Full record on ClinicalTrials.gov

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