MDX-060 Monoclonal Antibody in Treating Patients With Refractory or Relapsed Lymphoma

Phase I/II Open Label, Dose-Escalating Study of MDX-060 Administered Weekly for 4 Weeks in Patients With Refractory/Relapsed CD30 Lymphoma

RATIONALE: Monoclonal antibodies such as MDX-060 can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells.

PURPOSE: Phase I/II trial to study the effectiveness of MDX-060 monoclonal antibody in treating patients who have refractory or relapsed lymphoma.

OBJECTIVES:

• Determine the safety and tolerability of MDX-060 monoclonal antibody in patients with refractory or relapsed CD30-positive lymphoma.
• Determine the maximum tolerated dose and dose-limiting toxicity of this drug in these patients.
• Determine the pharmacokinetic profile of this drug in these patients.
• Determine, preliminarily, the efficacy (antilymphoma activity) of this drug in these patients.

OUTLINE: This is an open-label, multicenter, dose-escalation study.

Patients receive MDX-060 monoclonal antibody IV over 90 minutes once weekly for 4 weeks.

Cohorts of 3-6 patients receive escalating doses of MDX-060 monoclonal antibody until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional 16 patients are accrued and receive MDX-060 monoclonal antibody at the MTD.

Patients are followed monthly for 3 months and then every 3 months for 18 months or until disease progression.

PROJECTED ACCRUAL: A maximum of 40 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed B-cell or T-cell lymphoma

  • Hodgkin's lymphoma and anaplastic large cell lymphoma eligible
  • No HIV-associated lymphoma

• CD30-positive disease by biopsy, flow cytometry, or immunohistochemistry

  • At least 50% of malignant cells (specifically Reed-Sternberg cells for Hodgkin's lymphoma) must express CD30

• Must meet one of the following criteria for relapsed/refractory disease:

  • Relapsed after prior chemotherapy or radiotherapy and autologous or allogeneic bone marrow transplantation (if appropriate)

    • Relapsed disease must be within the prior irradiated field

  • Disease that is refractory to prior chemotherapy or radiotherapy with no other curative treatment option

    • Disease progression must be within the prior irradiated field

• Progressive and evaluable disease (measurable disease required for patients accrued on study after the maximum tolerated dose is determined)

PATIENT CHARACTERISTICS:

Age

• Over 12

Performance status

• ECOG 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

• WBC at least 1,500/mm^3*
• Neutrophil count at least 1,000/mm^3*
• Platelet count at least 75,000/mm^3*
• Hemoglobin at least 8.0 g/dL* NOTE: *Laboratory abnormalities attributable to organ involvement by lymphoma are allowed

Hepatic

• AST no greater than 2 times upper limit of normal (ULN)*
• Bilirubin no greater than 2.0 mg/dL (unless due to Gilbert's syndrome)*
• Hepatitis B surface antigen negative
• Hepatitis C antibody negative NOTE: *Laboratory abnormalities attributable to organ involvement by lymphoma are allowed

Renal

• Creatinine no greater than 2 times ULN* NOTE: *Laboratory abnormalities attributable to organ involvement by lymphoma are allowed

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective barrier contraception during and for 9 months after study participation

• HIV negative

• No other active malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

• No active significant infection

• No apparent opportunistic infection, as indicated by any of the following:

  • Purified protein derivative recently determined to be positive
  • Infectious infiltrate by chest x-ray
  • Recent changes in fever/chill patterns
  • New, unexplained neurological symptoms

• No underlying medical condition that would preclude receiving study therapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics
• No prior anti-CD30 antibody therapy
• No other concurrent biologic therapy

Chemotherapy

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy
• No concurrent chemotherapy

Endocrine therapy

• No concurrent systemic steroidal therapy (excluding physiologic doses)

Radiotherapy

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy
• No concurrent radiotherapy

Surgery

• Not specified

Other

• No other concurrent investigational agents