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

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: A Phase I/II Pilot Study of Ifosfamide, Carboplatin and Etoposide Therapy (ICE) and SGN-30 (NSC# 731636, IND#) in Children With CD30+ Recurrent Anaplastic Large Cell Lymphoma

Brief Summary: 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.

Detailed Summary:

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 u
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Response [ Time Frame: Week 4 ]

Anti tumor activity as assessed by computed tomography of neck/chest/abdomen/pelvis, positron emission tomography scan and/or gallium scan. 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.


Original Primary Outcome:

Current Secondary Outcome:

  • 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 ]
  • CD30 Concentrations Levels as Assessed by ELISA [ Time Frame: At baseline ]
    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 ]
    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 ]
    NPM-ALK expression will be summarized using appropriate descriptive statistics and reported with associated exact 95% confidence intervals.


Original Secondary Outcome:

Information By: National Cancer Institute (NCI)

Dates:
Date Received: July 19, 2006
Date Started: January 2007
Date Completion:
Last Updated: May 5, 2014
Last Verified: October 2011