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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00381940
Recruitment Status : Completed
First Posted : September 28, 2006
Results First Posted : April 10, 2014
Last Update Posted : January 28, 2021
Information provided by (Responsible Party):
National Cancer Institute (NCI)

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.

Condition or disease Intervention/treatment Phase
Adult Lymphocyte Depletion Hodgkin Lymphoma Adult Lymphocyte Predominant Hodgkin Lymphoma Adult Mixed Cellularity Hodgkin Lymphoma Adult Nodular Lymphocyte Predominant Hodgkin Lymphoma Adult Nodular Sclerosis Hodgkin Lymphoma Childhood Lymphocyte Depletion Hodgkin Lymphoma Childhood Lymphocyte Predominant Hodgkin Lymphoma Childhood Mixed Cellularity Hodgkin Lymphoma Childhood Nodular Lymphocyte Predominant Hodgkin Lymphoma Childhood Nodular Sclerosis Hodgkin Lymphoma Recurrent Adult Hodgkin Lymphoma Recurrent/Refractory Childhood Hodgkin Lymphoma Stage I Adult Hodgkin Lymphoma Stage I Childhood Hodgkin Lymphoma Stage II Adult Hodgkin Lymphoma Stage II Childhood Hodgkin Lymphoma Stage III Adult Hodgkin Lymphoma Stage III Childhood Hodgkin Lymphoma Stage IV Adult Hodgkin Lymphoma Stage IV Childhood Hodgkin Lymphoma Drug: ifosfamide Drug: bortezomib Drug: vinorelbine tartrate Biological: filgrastim Phase 2

Detailed Description:


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.


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 study treatment, patients are followed every 6 months for 2 years and then annually thereafter.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : January 2007
Actual Primary Completion Date : June 2008
Actual Study Completion Date : July 5, 2011

Arm Intervention/treatment
Experimental: Treatment (enzyme inhibitor therapy, chemotherapy)

Patients receive ifosfamide IV continuously over days 1-4, vinorelbine ditartrate IV over 6-10 minutes on days 1 and 5, bortezomib IV on days 1, 4, and 8, and filgrastim (G-CSF) IV or subcutaneously beginning on day 6 and continuing until blood counts recover or PBSC are harvested. Treatment repeats 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.

Drug: ifosfamide
Given IV
Other Names:
  • Cyfos
  • Holoxan
  • IFF
  • IFX
  • IPP

Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341

Drug: vinorelbine tartrate
Given IV
Other Names:
  • Eunades
  • navelbine ditartrate
  • NVB
  • VNB

Biological: filgrastim
Given IV or SC
Other Names:
  • G-CSF
  • Neupogen

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. Toxicity [ Time Frame: 4 weeks following completion of therapy ]
    Grade 3 and 4 non-hematologic toxicity during protocol therapy. The number of patients that experience CTC Version 4 grade 3 or higher non-hematologic at any time during protocol therapy

  2. Overall Response Rate [ Time Frame: After 2 cycles and 4 cycles ]
    Overall response includes complete response and partial response.

  3. 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.

  4. 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.

  5. Biological Markers [ Time Frame: Before, during, and after treatment ]
    Assessing baseline NF-kB protein levels in tumor tissue

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 29 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically confirmed Hodgkin's lymphoma at time of relapse or disease progression, meeting all of the following criteria:

    • Stage I-IV disease
    • No morphologically unclassifiable disease
  • Meets 1 of the following criteria:

    • Mixed cellularity
    • Lymphocytic depletion (LD)
    • LD, diffuse fibrosis
    • LD, reticular
    • Lymphocyte predominance (LP)
    • LP, diffuse
    • LP, nodular
    • Nodular sclerosis (NS)
    • NS, cellular phase
    • NS, lymphocytic predominance
    • NS, mixed cellularity
    • NS, LD
    • Not otherwise specified
  • Primary refractory disease OR disease in first relapse, except for the following:

    • Patients who achieved a complete response after treatment on protocol COG-AHOD0431 who experience a biopsy-proven recurrence after doxorubicin hydrochloride, vincristine, prednisone, and cyclophosphamide without involved-field radiotherapy
    • Patients on the observation-only arm of protocol COG-AHOD0431
  • Any measurable, focal mass lesion of a visceral organ (e.g., liver, spleen, or kidney)
  • Patients with metastatic disease to bone marrow and granulocytopenia, anemia, and/or thrombocytopenia are allowed provided both of the following criteria are met:

    • Platelet count ≥ 20,000/mm³ (platelet transfusion allowed)
    • Hemoglobin ≥ 8 g/dL (packed red blood cell transfusion allowed)
  • Karnofsky performance status (PS) 60-100% (for patients > 16 years of age) OR Lanksy PS 60-100% (for patients =< 16 years of age)
  • Life expectancy >= 2 months
  • Absolute neutrophil count >= 1,000/mm^3
  • Platelet count >= 75,000/mm^3 (transfusion independent) (for patients with no bone marrow involvement)
  • Creatinine =< 1.5 times upper limit of normal (ULN)
  • Creatinine clearance or radioisotope glomerular filtration rate >= 70 mL/min/1.73 m^2
  • AST and ALT =< 2.5 times ULN
  • Bilirubin =< 1.5 times ULN
  • Shortening fraction >= 27% by echocardiogram OR LVEF >= 50% by gated radionuclide study
  • Patients with a seizure disorder are eligible if on a nonenzyme-inducing anticonvulsant and seizures are well controlled
  • No CNS toxicity > grade 2
  • No serious intercurrent illnesses
  • No known hypersensitivity to E. coli-derived proteins, filgrastim (G-CSF), or any component of the study drugs
  • No peripheral neuropathy > grade 1
  • No known hypersensitivity to bortezomib, boron, or mannitol
  • No other concurrent chemotherapy or immunomodulating agents (including steroids)

    • Concurrent corticosteroids allowed for treatment or prophylaxis of anaphylactic reactions
    • No dexamethasone or aprepitant as an antiemetic
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Recovered from prior therapy
  • No prior bortezomib or other proteasome inhibitors
  • At least 3 weeks since prior chemotherapy (4 weeks for nitrosoureas)
  • More than 14 days since prior investigational drugs
  • No concurrent enzyme inducing anticonvulsants that alter p450 metabolism, including phenytoin, carbamazepine, phenobarbital, or other anticonvulsants

    • Benzodiazepine or gabapentin allowed

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00381940

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United States, Pennsylvania
Children's Oncology Group
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
National Cancer Institute (NCI)
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Principal Investigator: Terzah Horton Children's Oncology Group
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: National Cancer Institute (NCI) Identifier: NCT00381940    
Obsolete Identifiers: NCT01648439
Other Study ID Numbers: NCI-2009-01063
NCI-2009-01063 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
AHOD0521 ( Other Identifier: Children's Oncology Group )
AHOD0521 ( Other Identifier: CTEP )
U10CA098543 ( U.S. NIH Grant/Contract )
First Posted: September 28, 2006    Key Record Dates
Results First Posted: April 10, 2014
Last Update Posted: January 28, 2021
Last Verified: January 2021
Additional relevant MeSH terms:
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Hodgkin Disease
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Pathologic Processes
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents