Phase I Study of Ipilimumab (Anti-CTLA-4) in Children and Adolescents With Treatment-Resistant Cancer

NCT01445379 | Completed Phase 1

• 2 other identifiers: 08000708-C-0007
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 3

Brief Summary

This study will examine the safety and efficacy of ipilimumab-an experimental cancer treatment drug used to boost immune response-in children, adolescents, and young adults. Ipilimumab may allow immune cells to react to and destroy abnormal cells in the body, and has been tested in adults for a variety of cancers and has shown responses in some research studies. Because ipilimumab has not been tested in children, adolescents, or young adults, it is considered an experimental drug. The purposes of this research study are to determine the highest safe dose of ipilimumab for children, adolescents, and young adults with solid tumor cancers; examine its effectiveness and possible side effects; and better understand how the body and the immune system process it over time. Candidates must be between 2 and 21 years of age and must have solid malignant tumors that have been resistant to standard therapy. Volunteers will be screened with a medical history, a clinical examination, and computerized scans such as magnetic resonance imaging (MRI). Participants must have completed their last dose of chemotherapy, radiation, chemotherapy, or antibody or investigational therapy at least four weeks prior to enrollment. During the study, participants will receive an intravenous dose of ipilimumab once every three weeks. The infusion of ipilimumab will last 90 minutes, and the participant s vital signs will be monitored while the medicine is infusing and several times in the first 24 hours after the first dose (requiring a hospital stay during that time). If the participant is able to tolerate the first dose of ipilimumab, further doses (called cycles ) may be received on an outpatient basis. Blood and urine tests will be given on a regular basis during these cycles. After four cycles, participants whose tumors do not grow and who do not have unacceptable side effects will continue to receive ipilimumab every three months to maintain the current condition, until researchers conclude the study.

Conditions

Sarcoma; Wilm's Tumor; Lymphoma; Neuroblastoma

Keywords

Solid Tumor; Monoclonal Antibody; Pediatrics; Pharmacokinetics; Immunotherapy; Sarcoma; Lymphoma; Neuroblastoma

Outcome Measures

Primary Outcomes (2)

• To determine the tolerance and toxicity profile

  1 year

• Pharmacokinetics

  1 year

Secondary Outcomes (2)

• Evaluate immunomodulatory activity.

  2 years

• Quantify antitumor effects

  2 years

Study Arms (1)

1

EXPERIMENTAL

Ipilumumab (DSE) given on day 1 of 21 day cycle for 4 cycles, from cycle 5+ ipilumumab will be given \~every 12wks

Drug: Ipilimumab

Interventions

Ipilimumab DRUG

Dose Level Escalation: 1mg/kg, 3mg/kg, 5mg/kg, 10mg/kg

1

Eligibility Criteria

• Age: 3 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• AGE: Patients must be greater than or equal to 1 years and less than or equal to 21 years of age.
• DIAGNOSIS: Histologically confirmed solid tumors, which may include but are not limited to rhabdomyosarcoma and other soft tissue sarcomas, Ewing s sarcoma family of tumors, osteosarcoma, neuroblastoma, Wilm s tumor, Hodgkin's or non-Hodgkin's lymphoma. Patients with melanoma are eligible. Patients with a previous history of CNS metastases are eligible if the metastases have been treated with surgery and/or radiotherapy, are clinically stable as evidenced by no requirements for corticosteroids, the patient has no evolving neurologic deficits and no progression in residual brain abnormalities without specific therapy over 4 weeks.
• MEASURABLE/EVALUABLE DISEASE: Patients must have measurable or evaluable tumors.
• PRIOR THERAPY:
• The patient s cancer must have relapsed following or failed to respond to standard therapy and/or the patient s current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival.
• Patients must have completed their last dose of irradiation, chemotherapy, monoclonal antibody, or investigational therapy at least 4 weeks prior to enrollment. For patients who have undergone autologous stem cell transplantation, at least 3 months must have elapsed since transplant.
• Patients must have recovered from the toxic effects (to a grade 1 or less) of all prior therapy prior to enrollment, with the exception of the following:
• Hematological toxicity: recovery to levels required below
• Low electrolyte levels (Such individuals should receive appropriate supplementation)
• For patients on anticoagulant therapy or with pre-existing coagulation abnormalities, PT, PTT must return to baseline.
• Liver function tests must resolve to values required below
• Grade 3 hypoalbuminemia
• Alopecia
• Sterility
• PERFORMANCE STATUS: Patients greater than 10 years old must have a Karnofsky Score of greater than or equal to 50 and children less than 10 years old must have a Lansky score of greater than 50. Patients who are unable to walk because of paralysis or weakness, but who are up in a wheelchair will be considered ambulatory for the purpose of calculating the performance score.

You may not qualify if:

• Primary brain tumors
• Clinically significant unrelated systemic illness, such as serious infections or organ dysfunction, which in the judgment of the Principal or Associate Investigators would compromise the patient s ability to tolerate the agents in this trial or are likely to interfere with the study procedures or results. This includes but is not limited to:
• Critically-ill or medically unstable patients
• Patients with active infection or other significant systemic illness
• Patients with active diarrhea
• Patients with active eye inflammation, uveitis
• Presence of a symptomatic pleural effusion
• Patients with symptoms of congestive heart failure or uncontrolled cardiac rhythm disturbance
• History of malignant hyperthermia
• Concurrent or history of autoimmune disease excluding stable asthma
• Positive direct Coombs testing or history of hemolytic anemia
• Patients with a history of ongoing or intermittent bowel obstruction
• Concurrent radiation
• Patients with a history of allogeneic bone marrow transplantation.
• Untreated CNS metastases will render the patient ineligible however patients with a previous history of CNS metastases are eligible if: the metastases have been treated with surgery and/or radiotherapy, are clinically stable as evidenced by no requirements for corticosteroids, the patient has no evolving neurologic deficits and no progression in residual brain abnormalities without specific therapy are eligible one week post radiation or radiosurgery. Patients with asymptomatic subcentemeric CNS lesions will be eligible for trial if no immediate radiation or surgery.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (3)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

Location

Related Publications (3)

• Linet MS, Ries LA, Smith MA, Tarone RE, Devesa SS. Cancer surveillance series: recent trends in childhood cancer incidence and mortality in the United States. J Natl Cancer Inst. 1999 Jun 16;91(12):1051-8. doi: 10.1093/jnci/91.12.1051.

  PMID: 10379968 BACKGROUND

• Dunn GP, Old LJ, Schreiber RD. The three Es of cancer immunoediting. Annu Rev Immunol. 2004;22:329-60. doi: 10.1146/annurev.immunol.22.012703.104803.

  PMID: 15032581 BACKGROUND

• Zou W. Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat Rev Cancer. 2005 Apr;5(4):263-74. doi: 10.1038/nrc1586.

  PMID: 15776005 BACKGROUND

MeSH Terms

Conditions

Sarcoma; Wilms Tumor; Lymphoma; Neuroblastoma

Interventions

Ipilimumab

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Complex and Mixed; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplastic Syndromes, Hereditary; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Melinda S Merchant, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH

Study Record Dates

• First Submitted: September 30, 2011
• First Posted: October 3, 2011
• Study Start: October 1, 2007
• Primary Completion: April 18, 2014
• Study Completion: November 13, 2015
• Last Updated: December 17, 2019

Record last verified: 2015-11-13

Locations

US (3)