SGN-30 and Combination Chemotherapy in Treating Patients With Newly Diagnosed Anaplastic Large Cell Lymphoma

Study Overview
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Brief Summary
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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

Detailed Description
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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.

Official Title
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A Phase II Study of SGN-30 in Combination With CHOP in Anaplastic Large Cell Lymphoma

Conditions
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Anaplastic Large Cell Lymphoma

Intervention / Treatment
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* Drug: Cyclophosphamide
* Drug: Doxorubicin hydrochloride
* Drug: vincristine sulfate
* Drug: prednisone
* Drug: SGN-30


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SGN-30 + Combination Chemotherapy<br>Monoclonal antibody SGN-30 monotherapy: SGN-30 12 mg/kg weekly intravenously(IV) over 2 hours once weekly for 3 weeks. SGN-30 and CHOP chemotherapy: Beginning 1 week after completion of monoclonal antibody SGN-30 monotherapy, SGN-30 12 mg/kg 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. | Drug: Cyclophosphamide<br>* Given IV 750 mg/m^2 day 1<br>* Other names: Endoxana;Drug: Doxorubicin hydrochloride<br>* Given 50 mg/m^2 IV day 1<br>* Other names: Adriamycin RDF;Drug: vincristine sulfate<br>* Given 1.4 mg/m^2 IV<br>* Other names: Vincasar PFS;Drug: prednisone<br>* 100 mg orally daily days 1 - 5<br>* Other names: Deltra;Drug: SGN-30<br>* 12 mg/kg weekly IV over 2 hours once weekly for 3 weeks.<br>* Other names: Monoclonal antibody SGN-30 monotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Objective response rate (ORR) defined as the proportion of participants experiencing a Complete Response (CR) or Partial Response to a regimen of SGN-3- + CHOP using International Workshop Response Criteria (IWG) for Non-Hodgkin's Lymphomas (NHL). The IWG criteria (Cheson et al 2007) for a CR is a complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. A PR is at least a 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses, no increase should be observed in the size of other nodes, liver or spleen, and no new sites of disease should be observed. | Up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lymphoma, Large B-Cell, Diffuse, Neoplasms, non-Hodgkin's lymphoma, NHL, murine monoclonal antibody, mAb, SGN-30, CHOP, Cyclophosphamide, Doxorubicin Hydrochloride, Vincristine, Prednisone, anaplastic large cell lymphoma, Lymphoma, Lymphoma, Non-Hodgkin, Lymphoma, Large-Cell, Anaplastic, Neoplasms by Histologic Type, Lymphoproliferative Disorders, Lymphatic Diseases, Immunoproliferative Disorders, Immune System Diseases, Lymphoma, B-Cell, Lymphoma, T-Cell, Antibodies, Antibodies, Monoclonal, Immunologic Factors, Physiological Effects of Drugs, Pharmacologic Actions, Immunosuppressive Agents, Antirheumatic Agents, Therapeutic Uses, Antineoplastic Agents, Alkylating, Alkylating Agents, Molecular Mechanisms of Pharmacological Action, Antineoplastic Agents, Myeloablative Agonists, Antibiotics, Antineoplastic