Clinical Trial: Bortezomib, Ifosfamide, and Vinorelbine Tartrate in Treating Young Patients With Hodgkin's Lymphoma That is Recurrent or Did Not Respond to Previous Therapy

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase II Study of Bortezomib (Velcade, PS-341) in Combination With Ifosfamide/Vinorelbine in Pediatric Patients and Young Adults With Refractory/Recurrent Hodgkin Disease

Brief Summary: This phase II trial studies the side effects and efficacy of bortezomib with ifosfamide and vinorelbine in children and young adults with Hodgkin's lymphoma that was recurrent or did not respond to previous therapy. Bortezomib is an inhibitor of protein degradation. Bortezomib degrades short-lived regulatory proteins in the cell, and has been reported to increase the tumor cells. Bortezomib may increase the effectiveness of ifosfamide and vinorelbine (two standard drugs given to children with Hodgkin Lymphoma that has come back after initial treatment) by making cancer cells more sensitive to effectiveness of standard chemotherapy by preventing anti-death responses in these drugs. Giving bortezomib together with ifosfamide and vinorelbine tartrate should kill more cancer cells than are killed with ifosfamide and vinorelbine alone.

Detailed Summary:

PRIMARY OBJECTIVES:

I. Determine the efficacy and safety of bortezomib (as a chemosensitizing agent) in pediatric patients and young adults with primary refractory Hodgkin's lymphoma (HL) or HL in first relapse.

II. Determine the response rate in patients treated with bortezomib, ifosfamide, and vinorelbine ditartrate (vinorelbine tartrate) (IVB) and compare the response rate to the historical response rate in patients treated with ifosfamide and vinorelbine ditartrate alone.

SECONDARY OBJECTIVES:

I. Determine the overall response rate (complete and partial response) and induction success rate after 2 or 4 courses of therapy and the reinduction rate (complete response) after 4 courses of therapy.

II. Determine the proportion of patients able to mobilize sufficient hematopoietic stem cells (CD34+) after 2 courses of IVB.

OUTLINE: This is a multicenter, open-label, pilot study.

Patients receive ifosfamide intravenously (IV) continuously over days 1-4, vinorelbine tartrate IV over 6-10 minutes on days 1 and 5, and bortezomib intravenously on days 1, 4, and 8, and filgrastim (G-CSF) by vein or subcutaneously beginning on day 6 and continuing until blood counts recover or peripheral blood stem cells (PBSC) are harvested. Treatment cycles repeat every 21 days for up to 2 or 4 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo autologous PBSC harvesting according to institutional guidelines after the second course of therapy.

After completion of stu
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Complete Response (CR) [ Time Frame: After 2 cycles of treatment ]

CR is defined as at least 80% reduction in the sum of the products of the perpendicular diameters of each of the nodal masses or return to normal size, along with negative nuclear medicine imaging.


Original Primary Outcome:

Current Secondary Outcome:

  • Toxicity [ Time Frame: 4 weeks following completion of therapy ]
  • Overall Response Rate [ Time Frame: After 2 cycles and 4 cycles ]
    Overall response includes complete response and partial response.
  • Induction Success Rate [ Time Frame: After 2 cycles and 4 cycles ]
    Induction success is defined as achieving CR or PR without a targeted primary toxicity.
  • Rate of Successful PBSC Harvest [ Time Frame: After 2 cycles ]
    Success is defined as the ability to harvest 2x10^6 CD34+ cells/kg within 5 collection days.
  • Biological Markers [ Time Frame: Before, during, and after treatment ]
    Assessing baseline NF-kB protein levels in tumor tissue


Original Secondary Outcome:

Information By: National Cancer Institute (NCI)

Dates:
Date Received: September 26, 2006
Date Started: January 2007
Date Completion:
Last Updated: June 18, 2014
Last Verified: June 2014