Trial record 3 of 961 for:    "Hodgkin Disease"

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00381940
First received: September 26, 2006
Last updated: March 5, 2014
Last verified: January 2014
  Purpose

This phase II trial studied 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 Intervention 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 ditartrate
Biological: filgrastim
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 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:
  • Complete Response (CR) [ Time Frame: After 2 cycles of treatment ] [ Designated as safety issue: No ]
    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:
  • Toxicity [ Time Frame: 4 weeks following completion of therapy ] [ Designated as safety issue: Yes ]
  • Overall Response Rate [ Time Frame: After 2 cycles and 4 cycles ] [ Designated as safety issue: No ]
    Overall response includes complete response and partial response.

  • Induction Success Rate [ Time Frame: After 2 cycles and 4 cycles ] [ Designated as safety issue: No ]
    Induction success is defined as achieving CR or PR without a targeted primary toxicity.

  • Rate of Successful PBSC Harvest [ Time Frame: After 2 cycles ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Assessing baseline NF-kB protein levels in tumor tissue


Enrollment: 26
Study Start Date: January 2007
Study Completion Date: July 2011
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (ifosfamide, vinorelbine, bortezomib)

This was a single arm study that treated all patients with ifosfamide, vinorelbine, and bortezomib. Patients received ifosfamide IV (3000 mg/m2/day) continuously over days 1-4, vinorelbine ditartrate IV (25 mg/m2/dose) over 6-10 minutes on days 1 and 5, bortezomib IV (1.2 mg/m2/dose) 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 cycle 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:
  • Isophosphamide
  • Iphosphamide
  • Z4942
  • Ifex
  • NSC #109724
Drug: bortezomib
Given IV
Other Names:
  • Velcade
  • N-Pyrazinecarbonyl-L-phenylalanine-L-leucine boronic acid
  • PS-341
  • MLN341
  • LDP-341
  • NSC# 681239
  • IND # 58443
Drug: vinorelbine ditartrate
Given IV
Other Names:
  • Navelbine
  • NSC # 608210
Biological: filgrastim
Given IV or SC
Other Names:
  • Granulocyte Colony-Stimulating Factor
  • r-metHuG-CSF
  • G-CSF
  • Neupogen
  • NSC #614629

Detailed Description:

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

  Eligibility

Ages Eligible for Study:   1 Year to 29 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

Locations
United States, California
Children's Oncology Group
Arcadia, California, United States, 91006-3776
Sponsors and Collaborators
Investigators
Principal Investigator: Terzah Horton, MD, PhD Children's Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00381940     History of Changes
Obsolete Identifiers: NCT01648439
Other Study ID Numbers: NCI-2009-01063, NCI-2009-01063, CDR0000500142, COG-AHOD0521, AHOD0521, U10CA098543
Study First Received: September 26, 2006
Results First Received: January 8, 2014
Last Updated: March 5, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
H/RS
proteasome inhibition

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma
Sclerosis
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Pathologic Processes
Ifosfamide
Isophosphamide mustard
Vinorelbine
Bortezomib
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
Protease Inhibitors

ClinicalTrials.gov processed this record on April 17, 2014