SGN-30 and Combination Chemotherapy in Treating Patients With Newly Diagnosed Anaplastic Large Cell Lymphoma
SGN-30 and Combination Chemotherapy in Treating Patients With Newly Diagnosed Anaplastic Large Cell Lymphoma
This phase II trial is studying how well giving SGN-30 together with combination chemotherapy
 works in treating patients with newly diagnosed anaplastic large cell lymphoma. Monoclonal
 antibodies, such as SGN-30, can block cancer growth in different ways. Some block the ability
 of cancer cells to grow and spread. Others find cancer cells and help kill them or carry
 cancer-killing substances to them. Drugs used in chemotherapy work in different ways to stop
 the growth of cancer cells, either by killing the cells or by stopping them from dividing.
 Giving SGN-30 together with combination chemotherapy may kill more cancer cells
PRIMARY OBJECTIVES:

 I. Determine the efficacy of monoclonal antibody SGN-30 in combination with cyclophosphamide,
 doxorubicin hydrochloride, vincristine, and prednisone (CHOP) in patients with newly
 diagnosed anaplastic large cell lymphoma (ALCL).

 II. Determine the safety of combining monoclonal antibody SGN-30 with CHOP chemotherapy.

 SECONDARY OBJECTIVES:

 I. Determine whether monoclonal antibody SGN-30 can induce apoptosis of ALCL cells in vivo.

 II. Determine the response duration in patients treated with this regimen.

 III. Correlate response with pretreatment serum CD30 levels.

 IV. Determine response to single-agent monoclonal antibody SGN-30.

 OUTLINE: This is a multicenter study. Patients are stratified according to anaplastic large
 cell kinase (ALK) status (positive vs negative).

 Monoclonal antibody SGN-30 monotherapy: Patients receive monoclonal antibody SGN-30 IV over 2
 hours once weekly for 3 weeks.

 Monoclonal antibody SGN-30 and CHOP chemotherapy: Beginning 1 week after completion of
 monoclonal antibody SGN-30 monotherapy, patients receive monoclonal antibody SGN-30 IV over 2
 hours on day 1 and CHOP chemotherapy comprising cyclophosphamide IV over 1 hour, doxorubicin
 hydrochloride IV over 15 minutes, and vincristine IV over 15 minutes on day 1 and oral
 prednisone once daily on days 1-5. Treatment repeats every 21 days for 6-8 courses in the
 absence of disease progression or unacceptable toxicity.

 After completion of study treatment, patients are followed periodically for at least 5 years.
Inclusion Criteria:

 -  Histologically or cytologically confirmed systemic anaplastic large cell lymphoma
 (ALCL)

 -  Tissue available for the determination of anaplastic large cell kinase (ALK) status
 [t(2;5), ALK-NPM translocation] prior to study entry

 -  Prior steroids or topical treatments are allowed. Patients who are on chronic steroid
 therapy may receive concomitant steroids provided they have been on a stable dosage
 for at least 3 months prior to enrollment

 -  Measurable disease, defined as >= 1 lesion that can be accurately measured in >= 1
 dimension (longest diameter to be recorded) as >= 20 mm by conventional techniques or
 as >= 10 mm by spiral CT scan

 -  The Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 OR Karnofsky
 PS 70-100%

 -  White Blood Count (WBC) >= 3,000/mm³

 -  Absolute neutrophil count >= 1,500/mm³

 -  Platelet count >= 100,000/mm³ (unless due to lymphoma [i.e., splenomegaly and/or bone
 marrow involvement])

 -  Bilirubin =< 1.5 times upper limit of normal (ULN)

 -  AST or ALT =< 2.5 times ULN

 -  Creatinine =< 1.5 times ULN (unless due to lymphoma) OR creatinine clearance >=60
 mL/min

 -  Left ventricular ejection fraction (LVEF) >= 50%

 -  Not pregnant or nursing

 -  Negative pregnancy test

 -  Fertile patients must use effective contraception during and for 3 months after
 completion of study treatment

 Exclusion Criteria:

 -  No rapidly progressing disease or bulky disease, defined as a mass of > 7 cm in
 largest diameter

 -  No primary cutaneous ALCL

 -  No known brain metastases

 -  No concurrent combination antiretroviral therapy for HIV-positive patients

 -  No history of allergic reactions attributed to compounds of similar chemical or
 biological composition to monoclonal antibody SGN-30

 -  No uncontrolled intercurrent illness, including, but not limited to, any of the
 following:

 -  Ongoing or active infection

 -  Symptomatic congestive heart failure

 -  Unstable angina pectoris

 -  Cardiac arrhythmia

 -  Psychiatric illness or social situations that would preclude study compliance

 -  No prior or other concurrent malignancy with < 90% probability of survival at 5 years

 -  No other concurrent anticancer agents or therapies

 -  No prior chemotherapy for ALCL

 -  No other concurrent investigational agents