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Combination Chemotherapy in Treating Children With Refractory or Relapsed Hodgkin's Lymphoma

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00006760
First received: December 6, 2000
Last updated: May 1, 2013
Last verified: May 2013
History of Changes
  Purpose

RATIONALE: Drugs used in chemotherapy, such as ifosfamide and vinorelbine, work in different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy in treating children who have refractory or relapsed Hodgkin's lymphoma.


Condition Intervention Phase
Lymphoma
 Biological: filgrastim
Drug: ifosfamide
Drug: vinorelbine tartrate
 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 Pilot Study of Re-Induction Chemotherapy With Ifosfamide, and Vinorelbine (IV) in Children With Refractory/Relapsed Hodgkin's Disease

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Cardiac, hepatic, or renal toxicity [ Time Frame: Up to 1 month after completion of study treatment ] [ Designated as safety issue: Yes ]
  • Toxic death [ Time Frame: Up to 1 month after completion of study treatment ] [ Designated as safety issue: Yes ]
  • Hematological toxicity [ Time Frame: Up to 1 month after completion of study treatment ] [ Designated as safety issue: Yes ]
    The proportion of minimally pre-treated patients with cardiac, hepatic, renal, and hematologic toxicity will be determined. The toxic death rate will be calculated.


Secondary Outcome Measures:
  • Rate of successful PBSC harvest during re-induction defined as the ability to harvest 5 x 10^6 CD34+ cells/kg [ Time Frame: At 5 days after completion of study treatment ] [ Designated as safety issue: No ]
    Will be calculated.

  • Tumor response (CR or PR) [ Time Frame: Up to 1 year after completion of study treatment ] [ Designated as safety issue: No ]
  • Change in biologic markers [ Time Frame: From baseline to 1 year ] [ Designated as safety issue: No ]

Enrollment: 66
Study Start Date: May 2001
Study Completion Date: March 2012
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (ifosfamide, vinorelbine, filgrastim)
Patients receive ifosfamide IV over 24 hours on days 1-4 and vinorelbine tartrate IV over 6-10 minutes on days 1 and 5. Patients also receive filgrastim (G-CSF) subcutaneously or IV over 15-30 minutes beginning 24-36 hours after completion of vinorelbine and continuing daily until blood counts recover. Treatment repeats at least every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients may receive a third course of therapy at the discretion of the investigator. Heavily pretreated, high-risk patients who achieve a complete response are eligible for stem cell transplantation. Patients undergo peripheral blood stem cell (PBSC) collection during hematopoietic recovery after the second course of chemotherapy. Patients with sufficient PBSCs collected may undergo PBSC transplantation on protocol COG-AHOD0121.
 Biological: filgrastim
subcutaneously or IV over 15-30 minutes beginning 24-36 hours after completion of vinorelbine and continuing daily until blood counts recover.
Drug: ifosfamide
V over 24 hours on days 1-4
Drug: vinorelbine tartrate
IV over 6-10 minutes on days 1 and 5.

Detailed Description:

OBJECTIVES:

  • Determine the response rate (overall and within strata) in both minimally pretreated, low-risk and heavily pretreated, high-risk children with refractory or relapsed Hodgkin's lymphoma treated with ifosfamide and vinorelbine with filgrastim (G-CSF).
  • Determine the cardiac, hepatic, renal, and hematologic toxicity of this regimen in minimally-pretreated, low-risk patients.
  • Determine the toxic death rate in minimally pretreated, low-risk patients treated with this regimen.
  • Determine whether this treatment regimen can mobilize sufficient hematopoietic stem cells (CD34) for subsequent stem cell transplantation in minimally pretreated, low-risk patients.
  • Determine the incidence of hypermutability by longitudinal genotoxic biomonitoring of patients treated with this regimen.
  • Determine the prognostic significance of biological markers, including serum interleukin (IL)-10 receptor, serum IL-2 receptor, p53, and mdm-2 in patients treated with this regimen.

OUTLINE: This is a multicenter study. Patients are stratified by prior therapy (minimally pretreated, low-risk vs heavily pretreated, high-risk).

Patients receive ifosfamide IV over 24 hours on days 1-4 and vinorelbine IV over 6-10 minutes on days 1 and 5. Patients also receive filgrastim (G-CSF) subcutaneously or IV over 15-30 minutes beginning 24-36 hours after completion of vinorelbine and continuing daily until blood counts recover. Treatment repeats at least every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients may receive a third course of therapy at the discretion of the investigator.

Heavily pretreated, high-risk patients who achieve a complete response are eligible for stem cell transplantation. Patients undergo peripheral blood stem cell (PBSC) collection during hematopoietic recovery after the second course of chemotherapy. Patients with sufficient PBSCs collected may undergo PBSC transplantation on protocol COG-AHOD0121.

Patients are followed at 1, 6, and 12 months and then periodically thereafter.

PROJECTED ACCRUAL: A total of 66 patients will be accrued for this study within 1.5 years.

  Eligibility

Ages Eligible for Study:   up to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed refractory or relapsed Hodgkin's lymphoma

    • Mixed cellularity, not otherwise specified (NOS)
    • Lymphocytic depletion, NOS
    • Lymphocytic depletion, diffuse fibrosis
    • Lymphocytic depletion, reticular
    • Lymphocytic predominance, NOS
    • Lymphocytic predominance, diffuse
    • Lymphocytic predominance, nodular
    • Hodgkin's paragranuloma NOS
    • Hodgkin's granuloma
    • Hodgkin's sarcoma
    • Nodular sclerosis, NOS
    • Nodular sclerosis, cellular phase
    • Nodular sclerosis, lymphocytic predominance
    • Nodular sclerosis, mixed cellularity
    • Nodular sclerosis, lymphocytic depletion
    • Other (type not specified)
  • In first relapse
  • Metastasis to bone marrow with granulocytopenia, anemia, and/or thrombocytopenia allowed
  • Not enrolled on POG-9426 unless there is an extranodal site of recurrence

PATIENT CHARACTERISTICS:

Age:

  • Under 30 at diagnosis

Performance status:

  • Lansky 60-100% (for patients 16 years and under)
  • Karnofsky 60-100% (for patients over 16 years)

Life expectancy:

  • At least 2 months

Hematopoietic:

  • See Disease Characteristics
  • Absolute neutrophil count at least 1,000/mm^3
  • Platelet count at least 75,000/mm^3 (transfusion independent)

Hepatic:

  • Bilirubin no greater than 1.5 times normal
  • SGOT or SGPT less than 2.5 times normal

Renal:

  • Creatinine no greater than 1.5 times normal
  • Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min

Cardiovascular:

  • Shortening fraction at least 27% by echocardiogram OR
  • Ejection fraction at least 50% by gated radionuclide

Other:

  • No other concurrent serious illness
  • No known hypersensitivity to E. coli-derived proteins, filgrastim (G-CSF), or any other component of study drugs

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • No concurrent immunomodulating agents

Chemotherapy:

  • At least 2 weeks since prior chemotherapy (3 weeks for nitrosoureas) and recovered
  • No other concurrent anticancer chemotherapy

Endocrine therapy:

  • No concurrent steroids
  • No concurrent corticosteroids (e.g., dexamethasone)

Radiotherapy:

  • Recovered from prior radiotherapy

Surgery:

  • Not specified
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00006760

  Show 114 Study Locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
Study Chair: Tanya Trippett, MD Memorial Sloan-Kettering Cancer Center
Study Chair: Pedro A. de Alarcon, MD St. Jude Children's Research Hospital
  More Information

Additional Information:
Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00006760     History of Changes
Other Study ID Numbers: AHOD00P1, CCG-A5981, CDR0000068325, NCI-2012-02366, U10CA098543
Study First Received: December 6, 2000
Last Updated: May 1, 2013
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
recurrent/refractory childhood Hodgkin lymphoma
childhood lymphocyte predominant Hodgkin lymphoma
childhood lymphocyte depletion Hodgkin lymphoma
childhood nodular sclerosis Hodgkin lymphoma
childhood mixed cellularity Hodgkin lymphoma

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Ifosfamide
Isophosphamide mustard
Vinorelbine
Vinblastine
Lenograstim
 Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 16, 2013