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A Study of Intra-Patient Escalating Doses of MDX-010 Given Alone or in Combination With Two gp100 Peptides Emulsified With Montanide ISA-51 in the Treatment of Patients With Stage IV Melanoma


Phase 2
16 Years
N/A
Not Enrolling
Both
Melanoma (Skin)

Thank you

Trial Information

A Study of Intra-Patient Escalating Doses of MDX-010 Given Alone or in Combination With Two gp100 Peptides Emulsified With Montanide ISA-51 in the Treatment of Patients With Stage IV Melanoma


OBJECTIVES:

Primary

- Determine the clinical response in patients with stage IV melanoma treated with
escalating doses of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal
antibody (MDX-010) with or without gp100 peptides emulsified in Montanide ISA-51.

Secondary

- Determine the safety and toxicity profile of these regimens in these patients.

- Determine the immunologic response in patients treated with these regimens.

- Determine the pharmacokinetics of these regimens in these patients.

- Determine, in HLA-A*0201-positive patients, the differences in responses between
patients previously vaccinated with gp100 peptides and patients not previously
vaccinated.

OUTLINE: This is a 2-part, partially randomized study.

- Part I (closed as of 3/7/2005):

- HLA-A*0201-negative patients: Patients receive anti-cytotoxic
T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) IV over 90 minutes
on day 1. Treatment repeats every 3 weeks for up to 6 doses (3 courses of 3
escalating doses) in the absence of disease progression or unacceptable toxicity.

- HLA-A*0201-positive patients: Patients are stratified according to prior exogenous
gp100 peptide immunization (yes vs no). Patients are randomized to 1 of 2
treatment arms.

- Arm I: Patients receive MDX-010 in the same manner as the HLA-A*0201-negative
patients.

- Arm II: Patients receive MDX-010 as in arm I. Patients also receive
gp100:209-217 and gp100:280-288 peptides emulsified in Montanide ISA-51
subcutaneously immediately after each MDX-010 infusion.

- Part II:

- HLA-A*0201-negative patients (closed as of 3/7/2005): Patients receive MDX-010 as
in part I. Treatment repeats every 3 weeks for up to 4 doses (2 courses of 2
escalating doses, beginning with a higher dose level than in part I) in the
absence of disease progression or unacceptable toxicity.

- HLA-A*0201-positive patients: Patients are stratified and randomized as in part I.

- Arm I: Patients receive MDX-010 in the same manner as the HLA-A*0201-negative
patients.

- Arm II: Patients receive MDX-010 as in arm I. Patients also receive
gp100:209-217 and gp100:280-288 peptides emulsified in Montanide ISA-51
subcutaneously immediately after each MDX-010 infusion.

In both parts, patients with stable disease or a complete response (CR) after completing all
courses of MDX-010 may receive 1 additional course of therapy in the absence of unacceptable
toxicity. Patients achieving a partial response may continue to recieve treatment with
MDX-010 at the same dose, in the absence of unacceptable toxicity, until CR or until tumor
is no longer shrinking.

Patients are followed at 3 weeks, every 3 months for 1 year, every 6 months for 2 years, and
then annually thereafter.

PROJECTED ACCRUAL: A total of 35-179 patients (up to 35 for part I [closed as of 3/7/05] and
69-141 [23-47 per arm (arm I closed as of 3/7/05)] for part II) will be accrued for this
study within 3-4 years.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed stage IV melanoma

- Clinically evaluable or measurable disease

- No mucosal or ocular melanoma

PATIENT CHARACTERISTICS:

Age

- 16 and over

Performance status

- ECOG 0-2

Life expectancy

- At least 6 months

Hematopoietic

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 9 g/dL

- Hematocrit ≥ 28%

- WBC ≥ 2,500/mm^3

Hepatic

- AST ≤ 3 times upper limit of normal (ULN)

- Bilirubin ≤ ULN (< 3 mg/dL for patients with Gilbert's syndrome)

- Hepatitis B surface antigen negative

- Hepatitis C virus antibody negative

Renal

- Creatinine < 2 mg/dL

Immunologic

- HIV negative

- No history of any of the following:

- Inflammatory bowel disease

- Regional enteritis

- Connective tissue disorders (e.g., systemic lupus erythematosus)

- Rheumatoid arthritis

- Autoimmune inflammatory eye disease

- Sjögren's syndrome

- Inflammatory neurologic disorder (e.g., multiple sclerosis)

- No active infection

- No active autoimmune disease that may cause life-threatening symptoms or severe
organ/tissue damage

- Vitiligo, autoimmune thyroiditis, or skin rashes associated with prior therapy
are allowed if patient has recovered to grade 1 or less toxicity

- No systemic hypersensitivity to study agents

- Prior local reaction (e.g., delayed hypersensitivity or glaucomatous reactions)
to Montanide ISA-51 or gp100 injections allowed

- No autoimmune disease requiring active therapy with any form of steroid or
immunosuppressant

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No concurrent underlying medical condition that would preclude study participation

- No other malignancy within the past 5 years except adequately treated basal cell or
squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the
cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

- No prior anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody

- Prior therapy with gp100 peptides or any other immunotherapy allowed

Chemotherapy

- At least 6 weeks since prior nitrosoureas and recovered (toxicity no greater than
grade 1)

- No concurrent chemotherapy

Endocrine therapy

- At least 4 weeks since prior steroids

- No concurrent systemic, inhaled, optical, or topical corticosteroids

Radiotherapy

- Not specified

Surgery

- Not specified

Other

- At least 3 weeks since prior systemic therapy for melanoma and recovered (toxicity no
greater than grade 1)

- No concurrent immunosuppressive agents (e.g., cyclosporine)

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Primary Purpose: Treatment

Outcome Measure:

Objective response (partial and complete)

Safety Issue:

No

Principal Investigator

Steven A. Rosenberg, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

NCI - Surgery Branch

Authority:

United States: Federal Government

Study ID:

040083

NCT ID:

NCT00077532

Start Date:

March 2004

Completion Date:

February 2008

Related Keywords:

  • Melanoma (Skin)
  • stage IV melanoma
  • recurrent melanoma
  • Melanoma

Name

Location

Warren Grant Magnuson Clinical Center - NCI Clinical Studies SupportBethesda, Maryland  20892-1182