This phase I/II trial is studying the side effects and best dose of SGN-30 when given together with ifosfamide, carboplatin, and etoposide and to see how well they work in treating young patients with recurrent anaplastic large cell lymphoma. Drugs used in chemotherapy, such as ifosfamide, carboplatin, and etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. 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.

PRIMARY OBJECTIVES:

I. Define and describe the toxicities of monoclonal antibody SGN-30 alone (window) and in combination with ifosfamide, carboplatin, and etoposide (ICE) in pediatric patients with CD30-positive recurrent anaplastic large cell lymphoma.

II. Define, preliminarily, the antitumor activity of monoclonal antibody SGN-30 alone (window) and in combination with ICE in these patients.

SECONDARY OBJECTIVES:

I. Characterize the pharmacokinetics of monoclonal antibody SGN-30 in these patients.

II. Characterize the soluble CD30 concentrations at time of relapse in these patients.

III. Characterize the development of human antichimeric antibodies in these patients.

IV. Measure minimal residual disease in these patients.

OUTLINE: This is a multicenter, pilot, phase I, dose-finding study of monoclonal antibody SGN-30 followed by a phase II study.

Patients receive monoclonal antibody SGN-30 IV alone on day 1 in weeks 1-8. Beginning in week 5, patients receive ICE chemotherapy comprising ifosfamide IV over 2 hours on days 1-3, carboplatin IV over 1 hour on day 1, and etoposide IV over 1 hour on days 1-3. Treatment with ICE repeats every 3 weeks for 6 courses** in the absence of unacceptable toxicity. Patients also receive intrathecal therapy comprising methotrexate, cytarabine, and hydrocortisone once on day 29 (week 5).

NOTE: **Patients planning to undergo bone marrow transplantation (BMT) receive 2 courses of ICE only and then undergo BMT off study.

Cohorts of 3-6 patients receive a pre-determined dose of monoclonal antibody SGN-30 with possible dose de-escalation to 1 dose level below in the event of ≥ 2 of 6 patients experience dose-limiting toxicity (DLT). The dose at which ≤ 1 of 6 patients experience DLT will be used in a phase II study.

After completion of study treatment, patients are followed periodically for 5 years.

Inclusion Criteria:

• Histologically confirmed anaplastic large cell lymphoma

• CD30-positive disease

• Must be in first or second relapse

• Measurable disease

• No CNS disease

• Karnofsky performance status (PS) 60-100% (> 16 years of age) OR Lansky PS 60-100% (≤ 16 years of age)

• Absolute neutrophil count ≥ 1,000/mm³

• Platelet count ≥ 100,000/mm³ (transfusion independent)

  • Platelet count ≥ 20,000/mm³ if bone marrow involvement (platelet transfusions allowed)

• Hemoglobin ≥ 8.0 g/dL (RBC transfusion independent, unless bone marrow involvement)

• Creatinine adjusted according to age as follows:

  • No greater than 0.4 mg/dL (≤ 5 months)
  • No greater than 0.5 mg/dL (6 months-11 months)
  • No greater than 0.6 mg/dL (1 year-23 months)
  • No greater than 0.8 mg/dL (2 years-5 years)
  • No greater than 1.0 mg/dL (6 years-9 years)
  • No greater than 1.2 mg/dL (10 years-12 years)
  • No greater than 1.4 mg/dL (13 years and over [female])
  • No greater than 1.5 mg/dL (13 years to 15 years [male])
  • No greater than 1.7 mg/dL (16 years and over [male])

• Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)

• ALT < 3 times ULN

• Albumin ≥ 2 g/dL

• Not pregnant or nursing

• Negative pregnancy test

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

• No evidence of graft-vs-host disease

• No documented active infection requiring antibiotics

• No isolated bone recurrence

• Recovered from prior therapy

• At least 3 months since prior monoclonal antibody therapy

• At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas)

• At least 7 days since prior hematopoietic growth factor therapy

• At least 3 months since prior biologic (antineoplastic) agents

• At least 2 weeks since prior local palliative radiotherapy (small port)

• At least 3 months since prior total-body irradiation, craniospinal radiotherapy, or radiotherapy to ≥ 50% of the pelvis

• At least 6 weeks since other prior substantial bone marrow irradiation

• At least 2 months since prior stem cell transplantation or rescue

• No prior monoclonal antibody SGN-30

• Concurrent steroids allowed provided dose has been stable or decreasing for the past 7 days

• No concurrent immunosuppressive agents

• No concurrent dexamethasone as an antiemetic

• No other concurrent investigational drug or anticancer agents, including chemotherapy, radiotherapy, immunotherapy, or biological therapy