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

National Cancer Institute (NCI)

Status and phase: Terminated; Phase 2

Conditions: Anaplastic Large Cell Lymphoma

Treatments: Drug: Cyclophosphamide; Drug: vincristine sulfate; Drug: SGN-30; Drug: prednisone; Drug: Doxorubicin hydrochloride

Study type: Interventional

Funder types: NIH

Identifiers

NCT00365274

N01CM17003 (U.S. NIH Grant/Contract)

2005-0627 (Other Identifier)

N01CM62202 (U.S. NIH Grant/Contract)

NCI-2009-00162

Details and patient eligibility

About

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

Full 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.

Enrollment: 6 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

6 participants in 1 patient group

SGN-30 + Combination Chemotherapy

Experimental group

Description:

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.

Treatment:

Drug: Doxorubicin hydrochloride

Drug: prednisone

Drug: SGN-30

Drug: Cyclophosphamide

Drug: vincristine sulfate