Monoclonal Antibody Therapy in Treating Patients With Advanced or Recurrent Lymphoma

A Phase I, Multiple Dose Escalation Trial of Intravenous Humanized Anti-CD3 Antibody (HuM291) in Patients With CD3+ T-cell Lymphomas

RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

PURPOSE: Phase I trial to study the effectiveness of monoclonal antibody therapy in treating patients who have advanced or recurrent lymphoma.

OBJECTIVES:

• Determine the safety and tolerability of monoclonal antibody HuM291 in patients with advanced or recurrent CD3+ T-cell lymphomas.
• Evaluate the pharmacokinetics and pharmacodynamics of this treatment regimen in this patient population.
• Determine the response in these patients treated with this regimen.

OUTLINE: This is a dose-escalation study.

Patients receive monoclonal antibody HuM291 IV over 3 hours on days 1-4 in the absence of unacceptable toxicity. Patients achieving a partial response, complete response with recurrence, or stable disease may receive further therapy.

Cohorts of 3-6 patients receive escalating doses of monoclonal antibody HuM291 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 6 patients experience dose-limiting toxicity.

Patients are followed weekly for 1 month and then monthly for 3 months.

PROJECTED ACCRUAL: A total of 12-15 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed CD3+ T-cell lymphoma for which no standard curative therapy exists

  • Peripheral T-cell lymphoma

    • Recurrent and/or progressive disease after at least 1 prior therapy

  • Mycosis fungoides

    • Stage IB/IIA

      • Recurrent and/or progressive disease after at least 2 prior therapies

    • Stage IIB-IVB

      • Recurrent and/or progressive disease after at least 1 prior therapy

  • All other T-cell lymphomas

    • Recurrent and/or progressive disease after at least 1 prior therapy

• Evaluable disease

  • Any nodal site or mass lesion at least 1.5 cm in longest axis on physical exam or CT scan
  • Skin lesions at least 1 cm in longest axis for cutaneous lymphoma

• High numbers of circulating T-cells allowed

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2
• Karnofsky 50-100%

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 2,000/mm^3*
• Absolute neutrophil count at least 1,000/mm^3*
• Platelet count at least 75,000/mm^3* NOTE: * Unless due to lymphoma

Hepatic:

• Bilirubin no greater than 2.0 times normal*
• AST/ALT no greater than 2.5 times upper limit of normal*
• Hepatitis B and C negative NOTE: * Unless due to lymphoma

Renal:

• Not specified

Cardiovascular:

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other:

• No other uncontrolled illness
• No ongoing or active infection
• No other active malignancies except basal cell skin cancer or carcinoma in situ of the cervix
• HIV-1 negative
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

Biologic therapy:

• At least 60 days since prior humanized or chimeric antibody therapy

Chemotherapy:

• At least 3 weeks since prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 3 weeks since prior radiotherapy

Surgery:

• Not specified

Other:

• At least 30 days since prior investigational drugs or therapies