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Bortezomib, Ifosfamide, and Vinorelbine in Treating Young Patients With Hodgkin's Lymphoma That is Recurrent or Did Not Respond to Previous Therapy
This study has been suspended.
First Received: September 26, 2006   Last Updated: October 6, 2009   History of Changes
Sponsor: Children's Oncology Group
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00381940
  Purpose

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as ifosfamide and vinorelbine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Bortezomib may help ifosfamide and vinorelbine work better by making cancer cells more sensitive to the drugs. Giving bortezomib together with ifosfamide and vinorelbine may kill more cancer cells.

PURPOSE: This phase II trial is studying the side effects and how well giving bortezomib together with ifosfamide and vinorelbine works in treating young patients with Hodgkin's lymphoma that is recurrent or did not respond to previous therapy.


Condition Intervention Phase
Lymphoma
Biological: filgrastim
Drug: bortezomib
Drug: ifosfamide
Drug: vinorelbine ditartrate
Phase II

Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: A Phase II Study of Bortezomib (Velcade, PS-341, IND # 58443) in Combination With Ifosfamide/Vinorelbine in Pediatric Patients and Young Adults With Refractory/Recurrent Hodgkin Disease

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Toxicity [ Designated as safety issue: Yes ]
  • Complete response after 2 or 4 courses of treatment [ Designated as safety issue: No ]
  • Overall tumor response [ Designated as safety issue: No ]
  • Proportion of patients able to mobilize sufficient hematopoietic stem cells [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall response rate after 2 or 4 courses of treatment [ Designated as safety issue: No ]
  • Induction success rate [ Designated as safety issue: No ]

Estimated Enrollment: 48
Study Start Date: January 2007
Estimated Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

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

Secondary

  • 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.
  • 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 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 peripheral blood stem cells (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.

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

PROJECTED ACCRUAL: A total of 48 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   up to 29 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

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

    • Stage I-IV 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
    • No morphologically unclassifiable disease
  • Primary refractory disease OR disease in first relapse, except for the following:

    • Patients achieving 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
  • Measurable disease, defined as 1 of the following:

    • Any nodal mass with the longest traverse diameter > 2 cm
    • 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)

PATIENT CHARACTERISTICS:

  • 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/mm³
  • Platelet count ≥ 75,000/mm³ (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
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • 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
  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00381940

  Show 93 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Terzah M. Horton, MD, PhD Texas Children's Cancer Center
Investigator: Richard A. Drachtman, MD Cancer Institute of New Jersey
  More Information

Additional Information:
No publications provided

Responsible Party: Children's Oncology Group - Group Chair Office ( Gregory H. Reaman )
Study ID Numbers: CDR0000500142, COG-AHOD0521
Study First Received: September 26, 2006
Last Updated: October 6, 2009
ClinicalTrials.gov Identifier: NCT00381940     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
adult lymphocyte depletion Hodgkin lymphoma
adult lymphocyte predominant Hodgkin lymphoma
adult mixed cellularity Hodgkin lymphoma
adult nodular sclerosis Hodgkin lymphoma
childhood lymphocyte depletion Hodgkin lymphoma
childhood lymphocyte predominant Hodgkin lymphoma
childhood mixed cellularity 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
adult nodular lymphocyte predominant Hodgkin lymphoma
childhood nodular lymphocyte predominant Hodgkin lymphoma

Additional relevant MeSH terms:
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Vinblastine
Therapeutic Uses
Lymphoma
Hodgkin Disease
Alkylating Agents
Immunoproliferative Disorders
Neoplasms by Histologic Type
Immune System Diseases
Bortezomib
Mitosis Modulators
Enzyme Inhibitors
Antimitotic Agents
Pharmacologic Actions
Protease Inhibitors
Lymphatic Diseases
Ifosfamide
Neoplasms
Vinorelbine
Tubulin Modulators
Antineoplastic Agents, Alkylating
Lymphoproliferative Disorders
Antineoplastic Agents, Phytogenic
Isophosphamide mustard

ClinicalTrials.gov processed this record on November 20, 2009