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

Sponsor

City of Hope Medical Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT00863369

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arm

210

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: rituximab Drug: bortezomib Drug: gemcitabine hydrochloride Other: questionnaire administration	Phase 1/Phase 2

Detailed Description

OBJECTIVES:

Primary:

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

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

56 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (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

Actual Study Start Date :

Jun 29, 2005

Anticipated Primary Completion Date :

Dec 30, 2022

Anticipated Study Completion Date :

Dec 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

Safety and feasibility [One month after completion of study treatment]
Maximum tolerated dose [One month after completion of study treatment]

Secondary Outcome Measures

Response [One month after completion of study treatment]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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