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

Phase 2

Completed

• Conditions: Lymphoma
• Interventions: Biological: filgrastim; Drug: ifosfamide; Drug: vinorelbine tartrate

• Registration Number: NCT00006760
• Lead Sponsor: Children's Oncology Group

Brief Summary

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.

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.

Study Timeline

• Study First Submitted: 2000-12-06
• Study Start: 2001-05
• Study First Submitted QC: 2003-01-26
• Study First Posted: 2003-01-27
• Primary Completion: 2005-07
• Study Completion: 2012-03
• Status Verified: 2013-07
• Last Update Submitted: 2013-07-25
• Last Update Posted: 2013-07-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 66

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (ifosfamide, vinorelbine, filgrastim)	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.
Treatment (ifosfamide, vinorelbine, filgrastim)	vinorelbine tartrate	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.
Treatment (ifosfamide, vinorelbine, filgrastim)	ifosfamide	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.

Primary Outcome Measures

Name	Time	Method
Overall response rate	After 2 cycles	Overall response includes complete response (CR) or partial response (PR).

Secondary Outcome Measures

Name	Time	Method
Rate of successful PBSC harvest during re-induction defined as the ability to harvest 5 x 10^6 CD34+ cells/kg	After 2 cycles	Will be calculated.
Biologic markers	At enrollment and during/after therapy
Cardiac, hepatic, renal, hematologic toxicity	Within 1 month of completion of therapy
Toxic death	Within 1 month of Completion of therapy

Trial Locations

Locations (114)

Comprehensive Cancer Center at University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

Phoenix Children's Hospital; 🇺🇸 Phoenix, Arizona, United States

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences; 🇺🇸 Little Rock, Arkansas, United States

Southern California Permanente Medical Group; 🇺🇸 Downey, California, United States

Jonathan Jaques Children's Cancer Center at Miller Children's Hospital; 🇺🇸 Long Beach, California, United States

Jonsson Comprehensive Cancer Center at UCLA; 🇺🇸 Los Angeles, California, United States

Children's Hospital Central California; 🇺🇸 Madera, California, United States

Children's Hospital of Orange County; 🇺🇸 Orange, California, United States

Sutter Cancer Center; 🇺🇸 Sacramento, California, United States

Kaiser Permanente Medical Center - Oakland; 🇺🇸 Sacramento, California, United States

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