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

Phase 2

Terminated

Conditions: Anaplastic Large Cell Lymphoma

Interventions: Drug: Cyclophosphamide
Drug: Doxorubicin hydrochloride
Drug: vincristine sulfate
Drug: prednisone
Drug: SGN-30

Registration Number: NCT00365274

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 6

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
SGN-30 + Combination Chemotherapy	Cyclophosphamide	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.
SGN-30 + Combination Chemotherapy	Doxorubicin hydrochloride	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.
SGN-30 + Combination Chemotherapy	vincristine sulfate	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.
SGN-30 + Combination Chemotherapy	SGN-30	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.
SGN-30 + Combination Chemotherapy	prednisone	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.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	Up to 5 years	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.

Secondary Outcome Measures