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

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Terminated

CT.gov ID

NCT00039091

Collaborator

(none)

Enrollment

Location

Arm

68.7

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) 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 Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable Previously Treated Myelodysplastic Syndromes Recurrent Adult Acute Myeloid Leukemia Recurrent Melanoma Recurrent Non-small Cell Lung Cancer Recurrent Ovarian Epithelial Cancer Stage IV Melanoma Stage IV Non-small Cell Lung Cancer	Biological: ipilimumab	Phase 1

Detailed Description

PRIMARY OBJECTIVES:

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.
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.

Study Design

Study Type:

Interventional

Actual Enrollment :

26 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 (Anti-CTLA-4) Humanized Monoclonal Antibody (MDX-CTLA-4 NSC# 732442, Previously 720801) in Patients Previously Vaccinated With GM-CSF-Based Autologous Tumor Vaccines (CTEP Protocol Number P-5708) and Patients With Acute Myelogenous Leukemia/ Myelodysplasia, and Non-Small Cell Lung Cancer Who Have Not Received a Prior Vaccine

Study Start Date :

Mar 1, 2002

Actual Primary Completion Date :

Nov 1, 2007

Actual Study Completion Date :

Nov 21, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (ipilimumab) 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.	Biological: ipilimumab Given IV Other Names: anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody MDX-010 MDX-CTLA-4 monoclonal antibody CTLA-4

Arm

Intervention/Treatment

Experimental: Treatment (ipilimumab)

Biological: ipilimumab

Given IV

Other Names:

anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody

MDX-010

MDX-CTLA-4

monoclonal antibody CTLA-4

Outcome Measures

Primary Outcome Measures

Toxicities of ipilimumab, based on the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 [Up to 6 years]

Secondary Outcome Measures

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.
Proportion of patients who mount a brisk immune response, graded as absent, non-brisk, and brisk as described by Mihm [Up to 2 months post-treatment]
90% confidence intervals will be estimated.

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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