Bortezomib and Gemcitabine in Treating Patients With Relapsed Mantle Cell Lymphoma

Lymphoma Clinical Trial

Official title:

A Phase II Study of Bortezomib and Gemcitabine in Patients With Relapsed Mantle Cell Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00377052
• Other study ID #: I172
• Secondary ID: CAN-NCIC-IND172O
• Status: Completed
• Phase: Phase 2
• Start date: January 16, 2007
• Est. completion date: June 21, 2011

Study information

• Verified date: April 2020
• Source: Canadian Cancer Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. Drugs used in chemotherapy, such as gemcitabine, 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 gemcitabine work better by making cancer cells more sensitive to the drug.

PURPOSE: This phase II trial is studying how well giving bortezomib together with gemcitabine works in treating patients with relapsed mantle cell lymphoma.

Description:

OBJECTIVES:

• Determine the efficacy (response rate) of bortezomib and gemcitabine hydrochloride in patients with relapsed mantle cell lymphoma.

• Determine the toxicity of this regimen in these patients.

• Determine the time to progression and duration of response in patients treated with this regimen.

OUTLINE: This is a nonrandomized, multicenter 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 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 4 weeks and then every 3 months thereafter until relapse/progression.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: June 21, 2011
• Est. primary completion date: April 21, 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed mantle cell lymphoma

• Relapsed disease

• Not refractory to prior therapy

• Must have received 1-3 prior systemic chemotherapy regimens AND has had no disease progression while receiving chemotherapy or within 1 month of last dose of most recent therapy

• Clinically and/or radiologically documented disease

• At least 1 site of disease must be bidimensionally measurable by CT scan or MRI with = 1 lesion meeting 1 of the following criteria:

• Lymph nodes = 1.5 cm x 1.5 cm by spiral CT scan

• Non-nodal lesion = 1 cm x 1 cm by MRI, CT scan, or physical exam

• No nonmeasurable disease only

• No preexisting ascites or pleural effusion = grade 2

• No known CNS involvement by lymphoma

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2

• Life expectancy = 12 weeks

• Absolute granulocyte count = 1,500/mm³

• Platelet count = 75,000/mm³

• Creatinine = 1.5 times upper limit of normal (ULN)

• Bilirubin = 1.5 times ULN

• AST or ALT = 2.5 times ULN

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• LVEF = 45% by echocardiogram or MUGA

• No history of allergic reactions attributed to compounds containing boron or mannitol

• No preexisting edema = grade 2

• No preexisting neuropathy (sensory and/or pain) = grade 2

• No preexisting shortness of breath = grade 2

• No history of other malignancies, except adequately treated nonmelanoma skin cancer, curatively treated in situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for = 5 years

• No other serious illness or medical condition that would preclude compliance with study requirements, including any of the following:

• Serious uncontrolled infection

• Uncontrolled or severe cardiovascular disease, including any of the following:

• Myocardial infarction within the past 6 months

• New York Heart Association class III-IV heart failure

• Uncontrolled angina

• Clinically significant pericardial disease

• Cardiac amyloidosis

• Significant neurological disorder

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• At least 6 weeks since prior chemotherapy

• No prior radioactive monoclonal antibody therapy

• No prior bortezomib

• No prior investigational therapy (except for flavopiridol)

• No prior radiotherapy to > 25% of functioning bone marrow

• At least 4 weeks since prior radiotherapy and recovered

• Low-dose, nonmyelosuppressive radiotherapy may be allowed

• At least 2 weeks since prior major surgery

• No other concurrent anticancer therapy

• No concurrent corticosteroids

• No other concurrent cytotoxic chemotherapy

• No other concurrent investigational agents

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell

Intervention

Drug:
• bortezomib
1.0 mg/m2 IV; injection bolus (3-5 sec) Twice weekly x 2 weeks every three weeks
• gemcitabine hydrochloride
1000 mg/m2 IV; injection 30 minute infusion Once weekly x 2 weeks every three weeks

Locations

Country	Name	City	State
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	QEII Health Sciences Center	Halifax	Nova Scotia
Canada	QEII, CCR, Hematology Research	Halifax	Nova Scotia
Canada	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario
Canada	London Regional Cancer Program	London	Ontario
Canada	McGill University - Dept. Oncology	Montreal	Quebec
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	Odette Cancer Centre	Toronto	Ontario
Canada	Univ. Health Network-Princess Margaret Hospital	Toronto	Ontario
Canada	BCCA - Vancouver Cancer Centre	Vancouver	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba

Sponsors (1)

Lead Sponsor	Collaborator
NCIC Clinical Trials Group

Country where clinical trial is conducted

Canada, 

References & Publications (1)

Kouroukis CT, Fernandez LA, Crump M, Gascoyne RD, Chua NS, Buckstein R, Turner R, Assouline S, Klasa RJ, Walsh W, Powers J, Eisenhauer E. A phase II study of bortezomib and gemcitabine in relapsed mantle cell lymphoma from the National Cancer Institute of — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective tumor response (overall response rate with 95% confidence interval)		each cycle
Primary	Time to progression at median time		each cycle and every 3 months after treatment
Primary	Duration of response (median and range)		each cycle and every 3 months after treatment
Primary	Rate of stable disease and progressive disease		each cycle and every 3 months after treatment