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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00354107
First received: July 19, 2006
Last updated: May 5, 2014
Last verified: October 2011
  Purpose

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.


Condition Intervention Phase
Anaplastic Large Cell Lymphoma
Recurrent Childhood Anaplastic Large Cell Lymphoma
Biological: monoclonal antibody SGN-30
Drug: therapeutic hydrocortisone
Drug: ifosfamide
Drug: carboplatin
Drug: etoposide
Drug: methotrexate
Drug: cytarabine
Other: pharmacological study
Other: laboratory biomarker analysis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Response [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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.


Enrollment: 5
Study Start Date: January 2007
Study Completion Date: January 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (monoclonal antibody therapy, chemotherapy)

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).

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.

Biological: monoclonal antibody SGN-30
Given IV
Other Name: SGN-30
Drug: therapeutic hydrocortisone
Given IT
Other Names:
  • Aeroseb-HC
  • Barseb HC
  • Cetacort
  • Cort-Dome
  • Cortef
Drug: ifosfamide
Given IV
Other Names:
  • Cyfos
  • Holoxan
  • IFF
  • IFX
  • IPP
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: methotrexate
Given IT
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: cytarabine
Given IT
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   1 Year to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00354107

Locations
United States, Pennsylvania
Children's Oncology Group
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Investigators
Principal Investigator: John Sandlund Children's Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00354107     History of Changes
Other Study ID Numbers: NCI-2009-00407, NCI-2009-00407, COG-ANHL06P1, CDR0000486425, ANHL06P1, ANHL06P1, U10CA098543
Study First Received: July 19, 2006
Results First Received: October 24, 2013
Last Updated: May 5, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, Large-Cell, Anaplastic
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, T-Cell
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Cytarabine
Methotrexate
Etoposide phosphate
Isophosphamide mustard
Etoposide
Ifosfamide
Carboplatin
Cortisol succinate
Hydrocortisone acetate
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone
Hydrocortisone-17-butyrate
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on July 20, 2014