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Monoclonal Antibody Therapy in Treating Patients With Ovarian Epithelial Cancer, Melanoma, Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Non-Small Cell Lung Cancer

Phase 1
Terminated
Conditions
Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative
Recurrent Adult Acute Myeloid Leukemia
Recurrent Melanoma
Stage IV Melanoma
Stage IV Non-small Cell Lung Cancer
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
Interventions
Biological: ipilimumab
Registration Number
NCT00039091
Lead Sponsor
National Cancer Institute (NCI)
Brief Summary

This phase I trial is studying the side effects of monoclonal antibody therapy in treating patients with ovarian epithelial cancer, melanoma, acute myeloid leukemia, myelodysplastic syndrome, or non-small cell lung cancer. Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the safety of MDX-CTLA-4 in patients previously and not previously vaccinated with GM-CSF-based vaccines using lethally irradiated, autologous melanoma, ovarian cancer, acute myelogenous leukemia/myelodysplasia or lung cancer cells.

II. To identify preliminary evidence of biologic activity and efficacy.

OUTLINE:

Patients receive anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody IV over 90 minutes on day 1. Courses repeat every 2 months in the absence of disease progression or unacceptable toxicity.

Patients are followed monthly until disease progression.

PROJECTED ACCRUAL: A total of 48 patients (12 per disease type; 36 previously treated with a sargramostim (GM-CSF)-expressing autologous tumor cell vaccine and 12 not previously treated with this vaccine) will be accrued for this study.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
26
Inclusion Criteria
  • Patients previously vaccinated with GM-CSF-based vaccines using lethally irradiated, autologous melanoma, ovarian cancer, acute myelogenous leukemia/myelodysplasia, or non-small cell lung cancer cells; patients with acute myelogenous leukemia/myelodysplasia or non-small cell lung cancer who have not been vaccinated with an autologous, GM-CSF based vaccine
  • >= 4 weeks since treatment (chemo-, radiation, hormone, immuno-, etc., therapy)
  • Patients must have recovered from any acute toxicity associated with prior therapy
  • Measurable epithelial ovarian cancer, melanoma, AML/MDS, or non-small cell lung cancer
  • No standard curative treatment options
  • Not require immediate palliative therapy
  • Patients with epithelial ovarian cancer must have persistent or recurrent disease following primary surgery and primary chemotherapy
  • Patients with melanoma must be stage IV disease
  • Patients with AML/MDS, but without MDS, must be: a) in second relapse or b) first relapse with no option for bone marrow transplant or c) not a candidate for immunosuppressive chemotherapy due to age or comorbid disease
  • Patients with non-small cell lung cancer must be not curable by standard surgery, chemotherapy, and/or radiation
  • Life expectancy >= 12 weeks
  • ECOG performance status of 0, 1 or 2
  • Written informed consent
  • Due to the unknown effects of MDX-CTLA-4 on the fetus or nursing infant, pregnant or nursing women should not be included; women should be either: post-menopausal for at least 1 year; surgically incapable of bearing children; or utilizing an intrauterine device, and/or spermicide and barrier, for contraception; during the study, use of oral contraception alone is not acceptable; women of childbearing potential must have a negative serum beta-HCG pregnancy test conducted during screening, and a negative urinary beta-HCG pregnancy test conducted within 24 hours prior to treatment; due to the unknown effects of MDX-CTLA-4 on the fetus, men should not father children during the study
  • WBC > 1,000 cells/mm^3 (except for AML/MDS patients)
  • Serum creatinine < 2 mg/dL
  • Platelets > 75,000 cells/mm^3 (except for AML/MDS patients)
  • AST and ALT < 2 x UNL
  • Total bilirubin < 2 x UNL
Exclusion Criteria
  • Active infection
  • Autoimmune disease requiring immunosuppressive treatment
  • Any underlying medical condition which, in the principal investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of adverse events
  • Any concurrent medical condition requiring the use of systemic steroids (use of inhaled or topical steroids is acceptable)
  • CNS metastases, unless previously treated and stable for at least three months
  • Patients who have received prior treatment with MDX-CTLA-4

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Treatment (ipilimumab)ipilimumabPatients receive anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody IV over 90 minutes on day 1. Courses repeat every 2 months in the absence of disease progression or unacceptable toxicity.
Primary Outcome Measures
NameTimeMethod
Toxicities of ipilimumab, based on the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0Up to 6 years
Secondary Outcome Measures
NameTimeMethod
Proportion of patients who mount a brisk immune response, graded as absent, non-brisk, and brisk as described by MihmUp to 2 months post-treatment

90% confidence intervals will be estimated.

Overall clinical response rate (complete response [CR] plus partial response [PR]) based on the Response Evaluation Criteria in Solid Tumors (RECIST)Up to 6 years

90% confidence intervals will be estimated.

Trial Locations

Locations (1)

Dana-Farber Cancer Institute

🇺🇸

Boston, Massachusetts, United States

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