Bortezomib and Gemcitabine Hydrochloride in Treating Patients With Relapsed or Refractory Hodgkin's Lymphoma

This study has been completed.
Information provided by (Responsible Party):
Jonathan Friedberg, University of Rochester Identifier:
First received: December 6, 2005
Last updated: February 25, 2016
Last verified: February 2016

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 gemcitabine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with gemcitabine hydrochloride may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving bortezomib together with gemcitabine hydrochloride works in treating patients with relapsed or refractory Hodgkin's lymphoma.

Condition Intervention Phase
Drug: bortezomib
Drug: gemcitabine hydrochloride
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: Phase II Pilot Study of Bortezomib (VELCADE®) and Gemcitabine for Patients With Relapsed or Refractory Hodgkin's Lymphoma

Resource links provided by NLM:

Further study details as provided by University of Rochester:

Primary Outcome Measures:
  • Response Rate After 2 Courses of Therapy [ Time Frame: 21 Days/course for up to 2 courses ] [ Designated as safety issue: No ]
    Response was evaluated after two cycles of therapy using the 1999 Cheson response criteria. All responses were based on CT scans. The criteria that were developed include anatomic definitions of response, with normal lymph node size after treatment of 1.5 cm in the longest transverse diameter by computer-assisted tomography scan. A designation of complete response/unconfirmed was adopted to include patients with a greater than 75% reduction in tumor size after therapy but with a residual mass, to include patients-especially those with large-cell NHL-who may not have residual disease. For patients who had FDG-PET imaging, metabolic response was defined as a decrease in the standardized uptake value in target lesions (regions of abnormal FDG uptake on pretreatment FDG-PET images) to below three on posttreatment FDG-PET imaging). All PET scans were reviewed and interpreted by a single radiologist (SV).

Secondary Outcome Measures:
  • Change in Proteasome Activity Compared to Baseline [ Time Frame: baseline to day 1 ] [ Designated as safety issue: No ]
    Peripheral blood (40 ml) was collected on cycle 1, day 1 prebortezomib and 2 h post-bortezomib treatment and 1-2 weeks after cycle 2, day 11. The samples were refrigerated at 4C and processed within 36 h of collection. Frozen cell lysates were thawed and the proteasome activity in 10 ll was determined using a spectroflourometric 20S proteasome assay kit. Samples were run in triplicate on two separate days. The percent change between baseline and day 1 was calculated

Enrollment: 18
Study Start Date: April 2005
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bortezomib, Gemcitabine Hdrochloride Drug: bortezomib Drug: gemcitabine hydrochloride

Detailed Description:



  • Determine the overall response rate (partial and complete response) in patients with relapsed or refractory Hodgkin's lymphoma treated with bortezomib and gemcitabine hydrochloride.


  • Determine the safety and toxic effects of this regimen in these patients.
  • Determine the time to progression in patients treated with this regimen.
  • Correlate NF-kB inhibition and proteasome activity with response in patients treated with this regimen.

OUTLINE: This is a multicenter, pilot study.

Patients receive bortezomib IV on days 1, 4, 8, and 11 and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

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

PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.


Ages Eligible for Study:   18 Years to 120 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


  • Histologically confirmed Hodgkin's lymphoma

    • Recurrent or refractory disease after prior standard combination chemotherapy
  • Measurable disease, defined as ≥ 1 unidimensionally measurable lesion > 1 cm by physical exam or imaging studies
  • No history of non-Hodgkin's lymphoma
  • No history of other hematological malignancy


Performance status

  • ECOG 0-2

Life expectancy

  • Not specified


  • Platelet count ≥ 100,000/mm^3
  • Absolute neutrophil count ≥ 1,000/mm^3


  • Bilirubin ≤ 2 times upper limit of normal (ULN) (unless due to Gilbert's disease or involvement by Hodgkin's lymphoma)
  • AST ≤ 3 times ULN (unless due to involvement by Hodgkin's lymphoma)


  • Creatinine clearance ≥ 30 mL/min


  • Ejection fraction ≥ 40% by MUGA or echocardiogram (in patients with a history of cardiac disease)


  • Must not require supplemental oxygen therapy


  • No known HIV infection
  • No uncontrolled bacterial, viral, or fungal infection


  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No other malignancy requiring therapy
  • No peripheral neuropathy ≥ grade 2 within the past 14 days
  • No hypersensitivity to boron
  • No hypersensitivity to mannitol


Biologic therapy

  • More than 30 days since prior monoclonal antibody therapy for Hodgkin's lymphoma
  • More than 6 months since prior autologous stem cell transplantation
  • No prior allogeneic stem cell transplantation
  • No concurrent sargramostim (GM-CSF)
  • No concurrent pegfilgrastim or filgrastim (G-CSF)
  • No concurrent interleukin-11(oprelvekin)


  • See Disease Characteristics
  • More than 30 days since prior chemotherapy for Hodgkin's lymphoma
  • No prior treatment with gemcitabine hydrochloride

Endocrine therapy

  • More than 30 days since prior corticosteroid therapy for Hodgkin's lymphoma
  • No concurrent corticosteroid therapy


  • More than 30 days since prior radiotherapy for Hodgkin's lymphoma


  • No prior treatment with bortezomib
  • More than 14 days since prior investigational drugs
  • No other concurrent investigational agents
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00262860

United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, New York
James P. Wilmot Cancer Center at University of Rochester Medical Center
Rochester, New York, United States, 14642
Sponsors and Collaborators
University of Rochester
Principal Investigator: Jonathan W. Friedberg, MD James P. Wilmot Cancer Center
  More Information

Responsible Party: Jonathan Friedberg, Professor, University of Rochester Identifier: NCT00262860     History of Changes
Other Study ID Numbers: CDR0000448635  URCC-U9404  URCC-RSRB-10368  MILLENNIUM-VEL-03-079  LILLY-B9E-US-X433  DFCI-04388 
Study First Received: December 6, 2005
Results First Received: February 25, 2016
Last Updated: February 25, 2016
Health Authority: United States: Federal Government

Keywords provided by University of Rochester:
recurrent adult Hodgkin lymphoma

Additional relevant MeSH terms:
Hodgkin Disease
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms by Histologic Type
Anti-Infective Agents
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses processed this record on May 02, 2016