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

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

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.

Study Overview

• Status: Terminated
• Conditions: Anaplastic Large Cell Lymphoma; Recurrent Childhood Anaplastic Large Cell Lymphoma
• Intervention / Treatment: Other: laboratory biomarker analysis; Other: pharmacological study; Drug: etoposide; Drug: cytarabine; Drug: methotrexate; Drug: carboplatin; Drug: ifosfamide; Drug: therapeutic hydrocortisone; Biological: monoclonal antibody SGN-30

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Oncology Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 21 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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.

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response	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.	Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics of Monoclonal Antibody SGN-30 Assessed by Enzyme-linked Immunosorbent Assay (ELISA) Methods		At baseline, at weeks 1, 2, 5, 6, and 11
CD30 Concentrations Levels as Assessed by ELISA	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.	At baseline
Development of Human Antichimeric Antibodies by Using ELISA Method	Change in level from baseline to week 11 will be summarized using appropriate descriptive statistics and reported with associated exact 95% confidence intervals.	Change from baseline to week 11
Minimal Residual Disease by Using Southern Blotting or by Real-time Polymerase Chain Reaction (PCR)	NPM-ALK expression will be summarized using appropriate descriptive statistics and reported with associated exact 95% confidence intervals.	At baseline and weeks 5 and 11

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: John Sandlund, Children's Oncology Group

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (ACTUAL): January 1, 2010
• Study Completion (ACTUAL): January 1, 2010

Study Registration Dates

• First Submitted: July 19, 2006
• First Submitted That Met QC Criteria: July 19, 2006
• First Posted (ESTIMATE): July 20, 2006

Study Record Updates

• Last Update Posted (ACTUAL): March 14, 2018
• Last Update Submitted That Met QC Criteria: February 14, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease Attributes; Lymphoma, T-Cell; Lymphoma; Recurrence; Lymphoma, Non-Hodgkin; Lymphoma, Large-Cell, Anaplastic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Carboplatin; Etoposide; Etoposide phosphate; Antibodies; Ifosfamide; Antibodies, Monoclonal; Cytarabine; Methotrexate; Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Hydrocortisone hemisuccinate; Brentuximab Vedotin
• Other Study ID Numbers: NCI-2009-00407 (REGISTRY: CTRP (Clinical Trial Reporting Program)); U10CA098543 (U.S. NIH Grant/Contract); COG-ANHL06P1; CDR0000486425; ANHL06P1 (OTHER: CTEP)