Monoclonal Antibody Therapy in Treating Patients With Refractory Advanced Solid Tumors or Lymphoma

OBJECTIVES:

- Determine the maximum tolerated dose (MTD) of monoclonal antibody anti-alpha V beta 3
integrin (MEDI 522) in patients with refractory advanced solid tumors or lymphoma.

- Determine the safety and tolerability of this drug in these patients.

- Demonstrate significant binding of this drug to its molecular target in vivo in these
patients.

- Determine the effects of this drug on angiogenesis in these patients.

- Determine antitumor activity of this drug by measuring tumor size and glucose uptake in
these patients.

- Determine the pharmacokinetics of this drug in these patients.

- Determine a recommended phase II dose of this drug based on either the MTD or the
optimal biologic response in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive monoclonal antibody anti-alpha V beta 3 integrin (Medi 522) IV over 30
minutes weekly. Courses repeat every 4 weeks in the absence of disease progression or
unacceptable toxicity.

Cohorts of 6 patients receive escalating doses of Medi 522 until the maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6
patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: Approximately 6-30 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed solid tumor or lymphoma that is refractory
to currently available standard therapies or for which there are no curative
therapies

- No known brain metastases

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- ECOG 0-2

Life expectancy

- More than 12 weeks

Hematopoietic

- WBC at least 3,000/mm^3

- Absolute neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

- No prior bleeding disorder

Hepatic

- Bilirubin normal

- AST/ALT no greater than 2.5 times upper limit of normal

- INR/PTT normal

Renal

- Creatinine normal OR

- Creatinine clearance at least 60 mL/min

Cardiovascular

- No symptomatic congestive heart failure

- No unstable angina pectoris

- No cardiac arrhythmia

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 6 months after study
participation

- HIV negative

- T4 or thyroid stimulating hormone normal

- No thyroid disease

- No prior allergic reactions attributed to compounds of similar chemical or biologic
composition to study drug (e.g., rituximab or immunoglobulin G)

- No ongoing or active infection

- No other uncontrolled concurrent illness that would preclude study participation

- No psychiatric illness or social situation that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

- Not specified

Chemotherapy

- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
and recovered

Endocrine therapy

- Not specified

Radiotherapy

- More than 4 weeks since prior radiotherapy and recovered

Surgery

- More than 4 weeks since prior surgery

Other

- No other concurrent investigational agents

- No other concurrent anticancer agents or therapies (commercial or investigational)