Clinical trial NCT00030875: Bortezomib in Treating Patients With Mantle Cell Lymphoma
Official title: A Phase II Study Of PS-341 (NSC 681239) In Patients With Untreated Or Relapsed Mantle Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma
Keywords: stage I mantle cell lymphoma
contiguous stage II mantle cell lymphoma
noncontiguous stage II mantle cell lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma
recurrent mantle cell lymphoma
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
First posted: 2003-01-27
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Hamilton
country: Canada
facility: Margaret and Charles Juravinski Cancer Centre
state: Ontario
city: Kingston
country: Canada
facility: Kingston Regional Cancer Centre
state: Ontario
city: London
country: Canada
facility: Cancer Care Ontario-London Regional Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Toronto Sunnybrook Regional Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: Maisonneuve-Rosemont Hospital
state: Quebec
city: Montreal
country: Canada
facility: McGill University
state: Quebec
Study officials:
affiliation: Cross Cancer Institute at University of Alberta
name: Andrew R. Belch, MD
role: STUDY_CHAIR
References:
citation: Belch A, Kouroukis CT, Crump M, Sehn L, Gascoyne RD, Klasa R, Powers J, Wright J, Eisenhauer EA. A phase II study of bortezomib in mantle cell lymphoma: the National Cancer Institute of Canada Clinical Trials Group trial IND.150. Ann Oncol. 2007 Jan;18(1):116-121. doi: 10.1093/annonc/mdl316. Epub 2006 Sep 13.
citation: Belch A, Kouroukis CT, Crump M: Phase II trial of bortezomib in mantle cell lymphoma. [Abstract] Blood 104(11): A-608, 2004.
citation: Assouline S, Belch A, Sehn L, et al.: A phase II study of bortezomib in patients with mantle cell lymphoma. [Abstract] Blood 102 (11 Pt 1): A-3358, 2003.