Bortezomib and Gemcitabine in Treating Patients With Relapsed B-Cell Non-Hodgkin Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT00863369
First received: March 17, 2009
Last updated: December 16, 2013
Last verified: December 2013
  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 gemcitabine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving bortezomib together with gemcitabine hydrochloride and rituximab may kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of bortezomib and gemcitabine hydrochloride when given together with rituximab and to see how well they work in treating patients with progressive or relapsed B-cell non-Hodgkin lymphoma.


Condition Intervention Phase
Lymphoma
Biological: rituximab
Drug: bortezomib
Drug: gemcitabine hydrochloride
Other: questionnaire administration
Phase 1
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 I/II Study of VELCADE in Combination With Gemcitabine in Relapsed B-Cell Non-Hodgkin's Lymphoma

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Safety and feasibility [ Time Frame: One month after completion of study treatment ] [ Designated as safety issue: Yes ]
  • Maximum tolerated dose [ Time Frame: One month after completion of study treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Response [ Time Frame: One month after completion of study treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 56
Study Start Date: May 2005
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (bortezomib, gemcitabine hydrochloride, rituximab)
Patients receive bortezomib IV, gemcitabine hydrochloride IV over 3-4 hours, and rituximab IV on days 1 and 15. Treatment repeats every 28 days for at least 6 courses in the absence of disease progression or unacceptable toxicity.
Biological: rituximab
Given IV
Other Names:
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan
Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341
  • VELCADE
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
Other: questionnaire administration
Ancillary studies

Detailed Description:

OBJECTIVES:

Primary:

I. To evaluate the safety and feasibility of combining VELCADE (bortezomib) with gemcitabine (gemcitabine hydrochloride) in patients with recurrent lymphoma after standard therapy.

II. To define the maximum tolerated dose (MTD) of gemcitabine and Rituxan (rituximab) administered in combination with VELCADE given on a 21-day (old schema - Schema I) or 28-day (amended schema - Schema II) schedule.

Secondary:

I. To obtain preliminary data for response to this regimen in this patient population.

OUTLINE: This is a phase I, dose-escalation study of bortezomib and gemcitabine hydrochloride followed by a phase II study.

Patients receive bortezomib intravenously (IV), gemcitabine hydrochloride IV over 3-4 hours, and rituximab IV on days 1 and 15. Treatment repeats every 28 days for at least 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed intermediate or high grade B-cell Non-Hodgkin lymphoma with primary progressive or relapsed disease
  • Patients may have had up to 4 prior chemo-and-or radiation therapy regiments, including one autologous transplant based protocol; any prior therapy (chemotherapy or radiation) must have been completed at least 4 weeks prior to start of this protocol; for prior high-dose chemotherapy with stem cell transplant, a 6-week interval is required; all side effects must have resolved
  • Karnofsky performance status >= 60%
  • Life expectancy of greater than 3 months
  • Absolute neutrophil count >= 1,500 mm^3
  • Platelets >= 50,000 mm^3
  • Total bilirubin =< 1.5 mg/dl
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 x institutional upper limit of normal
  • Creatinine within normal institutional limits OR creatinine clearance >= 50 mL/min for creatinine levels above institutional normal (calculated or measured)
  • Cardiac ejection fraction of > 40% by echocardiogram or multi gated acquisition (MUGA) scan
  • Have no serious or intercurrent medical illness
  • Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
  • Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study
  • Male subject agrees to use an acceptable method for contraception for the duration of the study

Exclusion Criteria:

  • Patient has a platelet count of < 20 x 10^9/L with 7 days before enrollment
  • Patient has an absolute neutrophil count of < 1.0 x 10^9/L within 7 days before enrollment
  • Patient has a calculated or measured creatinine clearance of < 30 ml/min with 14 days before enrollment
  • Patient has >= Grade 2 peripheral neuropathy within 14 days before enrollment
  • Patient has hypersensitivity to bortezomib, boron, or mannitol
  • Female subject is pregnant or breastfeeding; confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening; pregnancy testing is not required for postmenopausal or surgically sterilized women
  • Patient has received other investigational drugs with 14 days before enrollment
  • Serious medical or psychiatric illness likely to interfere with participation in this clinical study
  • Patients who have had more than 4 prior different chemotherapy regimens will be excluded; patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for autologous transplant regimens) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Patients may not have previously received VELCADE or gemcitabine
  • Patients with active central nervous system (CNS) involvement are not eligible
  • Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  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 ClinicalTrials.gov identifier: NCT00863369

Locations
United States, California
City of Hope Medical Center
Duarte, California, United States, 91010-3000
South Pasadena Cancer Center
South Pasadena, California, United States, 91030
Sponsors and Collaborators
City of Hope Medical Center
Investigators
Principal Investigator: Leslie Popplewell, MD City of Hope Medical Center
  More Information

Additional Information:
No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT00863369     History of Changes
Other Study ID Numbers: 04115, P30CA033572, CHNMC-04115, MILLENNIUM-CHNMC-04115, CDR0000637492, NCI-2010-00925
Study First Received: March 17, 2009
Last Updated: December 16, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by City of Hope Medical Center:
recurrent adult Burkitt lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult grade III lymphomatoid granulomatosis
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent grade 3 follicular lymphoma
recurrent mantle cell lymphoma
adult grade III lymphomatoid granulomatosis

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antibodies, Monoclonal
Gemcitabine
Rituximab
Bortezomib
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Radiation-Sensitizing Agents
Antirheumatic Agents
Protease Inhibitors

ClinicalTrials.gov processed this record on July 29, 2014