View Clinical Trial (Medical Research Study)
A Phase I Study of Ipilimumab (Anti-CTLA-4) in Children, Adolescents and Young Adults With Treatment Refractory Cancer
| City: |
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Bethesda |
| State: |
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Maryland |
| Zip Code: |
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20892 |
| Conditions: |
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Adult Malignant Fibrous Histiocytoma of Bone - Childhood Malignant Fibrous Histiocytoma of Bone - Kidney Cancer - Lymphoma - Melanoma (Skin) - Neuroblastoma - Sarcoma - Unspecified Adult Solid Tumor, Protocol Specific - Unspecified Childhood Solid Tumor, |
| Purpose: |
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RATIONALE: Monoclonal antibodies, such as ipilimumab, can block cancer growth in different
ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells
and help kill them or carry cancer-killing substances to them.
PURPOSE: This phase I trial is studying the side effects and best dose of ipilimumab in
treating children, adolescents, and young adults with advanced or refractory solid tumors,
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| Study Summary: |
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OBJECTIVES:
Primary
- To determine the tolerance and toxicity profile of ipilimumab at a range of doses up
to, but not exceeding, the highest dose tolerated in patients 21 years of age or
younger with advanced or refractory solid tumors.
- To assess the pharmacokinetics of ipilimumab in patients with solid tumors refractory
to standard therapy.
Secondary
- To quantify antitumor effects of ipilimumab in these patients.
- To evaluate the immunomodulatory activity of ipilimumab in these patients.
OUTLINE:
- Induction therapy: Patients receive ipilimumab IV over 90 minutes on day 1. Treatment
repeats every 21 days for 4 courses in the absence of disease progression or
unacceptable toxicity.
- Maintenance therapy: Beginning in course 5 and all subsequent courses, patients receive
ipilimumab IV over 90 minutes on day 1 every 12 weeks for up to 2 years in the absence
of disease progression or unacceptable toxicity.
Patients undergo blood sample collection periodically for pharmacokinetic studies. Samples
are analyzed for plasma concentrations of ipilimumab via enzyme-linked immunosorbent assay.
Previously collected tumor tissue will be obtained and analyzed for the presence of CD4,
CD8, FoxP3, Granzyme B, and IDO expression via immunohistochemistry. Samples may be banked
for future research studies.
After completion of study treatment, patients are followed at 3 weeks.
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| Criteria: |
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DISEASE CHARACTERISTICS:
Inclusion criteria:
- Histologically confirmed solid tumors including, but not limited to, any of the
following:
- Melanoma
- Rhabdomyosarcoma or other soft tissue sarcomas
- Ewing sarcoma family of tumors
- Osteosarcoma
- Neuroblastoma
- Wilms tumor
- Hodgkin or non-Hodgkin lymphoma
- Measurable or evaluable disease
- Must meet at least 1 of the following criteria:
- Relapsed disease
- Failed to respond to standard therapy
- No known curative therapy for current disease state or no known curative therapy
proven to prolong survival
- Patients with a prior history of CNS metastases are eligible provided the following
criteria are met:
- Metastases have been treated with surgery and/or radiotherapy
- Clinically stable as evidenced by no requirements for corticosteroids
- No evolving neurologic deficits and no progression in residual brain
abnormalities without specific therapy over the past 4 weeks
Exclusion criteria:
- Primary brain tumors
- Untreated CNS metastases
PATIENT CHARACTERISTICS:
Inclusion criteria:
- Karnofsky performance status (PS) ≥ 50% (patients > 10 years of age) OR Lansky PS >
50% (patients ≤ 10 years of age)
- 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
- Peripheral absolute granulocyte count ≥ 1,000/μL
- Hemoglobin ≥ 8 g/dL
- Platelet count ≥ 75,000/μL (transfusion independent)
- AST and ALT ≤ 2.5 times upper limit of normal
- Direct bilirubin normal
- Creatinine clearance ≥ 70 mL/min OR maximum serum creatinine meeting the following
criteria:
- 0.8 mg/dL (≤ 5 years of age)
- 1.0 mg/dL (> 5 or ≤ 10 years of age)
- 1.2 mg/dL (> 10 or ≤ 15 years of age)
- 1.5 mg/dL (> 15 years of age)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 60 days after
completion of study therapy
- Negative hepatitis A (anti-hepatitis A IgM), B, (HBsAg), and C (anti-HCV)
- A positive hepatitis B titer does not exclude a patient if immunization has been
performed and if there is no history of disease
- Negative HIV
Exclusion criteria:
- Clinically significant unrelated systemic illness, such as serious infections or
organ dysfunction, which in the judgment of the principle 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 including, but not limited
to, any of the following:
- Critically ill or medically unstable
- Active infection or other significant systemic illness
- Active diarrhea
- Active eye inflammation or uveitis
- Presence of a symptomatic pleural effusion
- Symptoms of congestive heart failure or uncontrolled cardiac rhythm disturbance
- History of malignant hyperthermia
- Prior or concurrent autoimmune disease excluding stable asthma
- Positive direct Coombs testing or history of hemolytic anemia
- History of ongoing or intermittent bowel obstruction
- Autoimmune disease, including any of the following:
- Hemolytic anemia
- Ulcerative or hemorrhagic colitis
- Endocrine disorders (e.g., thyroiditis, hyperthyroidism, hypothyroidism,
autoimmune hypophysitis/hypopituitarism, or adrenal insufficiency)
- Sarcoid granuloma
- Myasthenia gravis
- Polymyositis
- Guillain-Barre syndrome
PRIOR CONCURRENT THERAPY:
Inclusion criteria:
- See Disease Characteristics
- Must have recovered from the toxic effects (grade ≤ 1) of all prior therapy except
for any of the following:
- Hematological toxicity
- Low electrolyte levels (such individuals should receive appropriate
supplementation)
- For patients on anticoagulant therapy or with pre-existing coagulation
abnormalities, PT and PTT must return to baseline
- Liver function tests must be resolved
- Grade 3 hypoalbuminemia
- Alopecia
- Sterility
- At least 4 weeks since prior chemotherapy, monoclonal antibody, or investigational
therapy
- At least 1 week since prior radiotherapy
- At least 3 months since prior autologous stem cell transplantation
Exclusion criteria
- Concurrent radiotherapy
- Prior allogeneic bone marrow transplantation
- Prior ipilimumab
- Treatment with any of the following within 14 days prior to study :
- Systemic corticosteroid therapy
- Erythropoietin
- Retinoic acid
- Fenretinide
- Interferons or interleukins
- Cytokine-fusion proteins
- Growth hormone
- Intravenous immunoglobulin
- Treatment with myeloid growth factors (G-CSF [filgrastim]/GM-CSF [sargramostim])
within 72 hours prior to study
- Concurrent chemotherapy or immunotherapy
- Any other concurrent investigational agent
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| NCT ID: |
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NCT00556881 |
| Primary Contact: |
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Principal Investigator
Melinda Merchant, MD
NCI - Pediatric Oncology Branch
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| Backup Contact: |
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N/A |
| Location Contact: |
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Bethesda, Maryland 20892
United States
Clinical Trials Office - Warren Grant Magnusen Clinical Center
Phone: 888-NCI-1937
Site Status: Recruiting |
| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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May 24, 2013 |
| Modifications to this listing: |
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