Bortezomib and Gemcitabine in Treating Patients With Relapsed Mantle Cell Lymphoma

NCIC Clinical Trials Group

Status and phase: Completed; Phase 2

Conditions: Lymphoma

Treatments: Drug: gemcitabine hydrochloride; Drug: bortezomib

Study type: Interventional

Funder types: NETWORK

Identifiers

NCT00377052

CDR0000493021 (Other Identifier)

B9E-CA-0485 (Other Identifier)

CAN-NCIC-IND172 (Registry Identifier)

I172

ORTHO-CAN-NCIC-IND172 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 29 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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29 participants in 1 patient group

Bortezomib + Gemcitabine

Experimental group

Treatment:

Drug: bortezomib

Drug: gemcitabine hydrochloride