Ifosfamide, Carboplatin, Etoposide, and SGN-30 in Treating Young Patients With Recurrent Anaplastic Large Cell Lymphoma

• Toxicity of toxicities of SGN-30 alone and in combination with ICE using the National Cancer Institute Common Terminology Criteria for Adverse Events v. 3.0 [ Time Frame: Weekly for up to 23 weeks ] [ Designated as safety issue: Yes ]
  
• Antitumor activity as assessed by computed tomography of neck/chest/abdomen/pelvis, positron emission tomography scan and/or gallium scan [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  Assessed by physical examination appropriate imaging studies. Bone marrow aspirate/biopsy must be normal and any macroscopic nodules in any organs detectable on imaging techniques should no longer be present. Gallium scans must be negative if initially positive.
  
  

• Pharmacokinetics of monoclonal antibody SGN-30 assessed by enzyme-linked immunosorbent assay (ELISA) methods [ Time Frame: At baseline, at weeks 1, 2, 5, 6, and 11 ] [ Designated as safety issue: No ]
  
• CD30 concentrations levels as assessed by ELISA [ Time Frame: At baseline ] [ Designated as safety issue: No ]
  Summarized using appropriate descriptive statistics and reported with associated exact 95% confidence intervals. Although the limited sample size precludes formal hypothesis testing, exploratory analysis of the association between soluble CD30 levels and PK parameters and response will be performed.
  
  
• Development of human antichimeric antibodies by using ELISA method [ Time Frame: Change from baseline to week 11 ] [ Designated as safety issue: No ]
  Change in level from baseline to week 11 will be summarized using appropriate descriptive statistics and reported with associated exact 95% confidence intervals.
  
  
• Minimal residual disease by using southern blotting or by real-time polymerase chain reaction (PCR) [ Time Frame: At baseline and weeks 5 and 11 ] [ Designated as safety issue: No ]
  NPM-ALK expression will be summarized using appropriate descriptive statistics and reported with associated exact 95% confidence intervals.
  
  

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.