Bortezomib in Treating Patients With Mantle Cell Lymphoma

NCIC Clinical Trials Group

Status and phase: Completed; Phase 2

Conditions: Lymphoma

Treatments: Drug: bortezomib

Study type: Interventional

Funder types: NETWORK

Identifiers

NCT00030875

CAN-NCIC-IND150 (Other Identifier)

CDR0000069207 (Other Identifier)

I150

Details and patient eligibility

About

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth.

PURPOSE: Phase II trial to study the effectiveness of bortezomib in treating patients who have previously untreated or relapsed mantle cell lymphoma.

Full description

OBJECTIVES:

• Determine the efficacy of bortezomib, in terms of response rate, in patients with previously untreated or relapsed mantle cell lymphoma.
• Determine the toxicity of this drug in these patients.
• Correlate suppression of 20S proteasome levels with toxicity of and response to this drug in these patients.
• Determine the time to progression and response duration in patients treated with this drug.

OUTLINE: This is a nonrandomized, multicenter study.

Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients with complete response (CR) receive 2 courses beyond documentation of CR. Patients with stable disease receive a maximum of 4 courses. Patients with partial response (PR) continue therapy until disease progression or for 2 courses beyond documentation of stable PR.

Patients are followed at 4 weeks and then every 3 months until disease progression.

PROJECTED ACCRUAL: A total of 14-30 patients will be accrued for this study within 18-24 months.

Enrollment: 30 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed relapsed or untreated mantle cell lymphoma

  • No refractory disease defined as progression while on chemotherapy or within 1 month after completion of chemotherapy

• At least 1 bidimensionally measurable disease site*

  • Lymph nodes at least 1.5 cm by 1.5 cm by spiral CT scan OR
  • Non-nodal lesions (e.g., skin lesion or nodules) at least 1 cm by 1 cm by MRI, CT scan, or physical exam NOTE: *Bone lesions are not considered bidimensionally measurable disease

• No pre-existing ascites or pleural effusion

• No known CNS involvement by lymphoma

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 12 weeks

Hematopoietic:

• Absolute granulocyte count at least 1,500/mm^3
• Platelet count at least 75,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST or ALT no greater than 2.5 times ULN

Renal:

• Creatinine no greater than 1.5 times ULN

Cardiovascular

• LVEF at least 45% by echocardiogram or MUGA

Pulmonary

• No pre-existing shortness of breath greater than grade 1

Other:

• No uncontrolled bacterial, fungal, or viral infections
• No pre-existing edema greater than grade 1
• No pre-existing neuropathy greater than grade 1
• No other malignancy within the past 5 years except adequately treated nonmelanoma skin cancer or carcinoma in situ of the cervix
• No other serious illness or medical condition that would preclude study compliance
• No geographical conditions that would preclude study compliance
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Chemotherapy
• Prior rituximab allowed
• No prior radioactive monoclonal antibody therapy

Chemotherapy:

• See Disease Characteristics

• No prior high-dose chemotherapy with stem cell transplantation

• No more than 2 prior systemic chemotherapy regimens

  • Same chemotherapy combination given for first-line and second-line therapy is considered 2 regimens

• No prior flavopiridol

• At least 6 weeks since prior chemotherapy

• No concurrent cytotoxic chemotherapy

Endocrine therapy:

• No concurrent corticosteroids

Radiotherapy:

• No prior radiotherapy to 25% or more of functioning bone marrow
• At least 4 weeks since prior radiotherapy (except low-dose nonmyelosuppressive radiotherapy) and recovered
• No concurrent radiotherapy to the sole site of measurable disease

Surgery:

• At least 2 weeks since prior major surgery

Other:

• No prior investigational therapy
• No other concurrent anticancer therapy
• No other concurrent investigational anticancer therapy

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)