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.

Condition	Treatment or Intervention	Phase
recurrent adult Hodgkin's lymphoma recurrent/refractory childhood Hodgkin's lymphoma anaplastic large cell lymphoma recurrent adult diffuse large cell lymphoma recurrent childhood large cell lymphoma recurrent cutaneous T-cell lymphoma	Drug: MDX-060 monoclonal antibody  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: monoclonal antibody therapy	Phase I Phase II

Further Study Details: 

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.

Ages Eligible for Study:  12 Years and above,  Genders Eligible for Study:  Both

Criteria

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

Minnesota
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States; Recruiting
New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States; Recruiting
Ohio
      Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University, Columbus,  Ohio,  43210-1240,  United States; Recruiting

Study chairs or principal investigators

Steven M. Horwitz, MD,  Study Chair,  Memorial Sloan-Kettering Cancer Center   

Study ID Numbers:  CDR0000298995; MSKCC-02121; MDX-060-01; NCT00059995
Record last reviewed:  April 2003
Last Updated:  January 6, 2005
Record first received:  May 6, 2003
ClinicalTrials.gov Identifier:  NCT00059995
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08