Bortezomib in Treating Patients With Lymphoproliferative Disorders

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00023764
First received: September 13, 2001
Last updated: April 25, 2014
Last verified: December 2012
  Purpose

Phase II trial to study the effectiveness of bortezomib in treating patients who have low-grade lymphoproliferative disorders. Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth.


Condition Intervention Phase
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Drug: bortezomib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of PS-341 in Low Grade Lymphoproliferative Disorders

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Response Rate [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    The response probability will be estimated. The 95% confidence interval will be provided.


Secondary Outcome Measures:
  • Duration of Response [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    The mean and median duration of response will be calculated from the observed duration. The Kaplan-Meier curve will be generated.

  • Progression Free Survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    The mean and median progression free survival will be calculated from the observed duration. The Kaplan-Meier curve will be generated.

  • Overall Survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    The mean and median duration of overall survival will be calculated from the observed duration. The Kaplan-Meier curve will be generated.


Enrollment: 104
Study Start Date: June 2001
Study Completion Date: March 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive an infusion of bortezomib over 3-5 seconds once weekly for 4 weeks. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients who achieve at least a partial response lasting at least 6 months may receive retreatment.
Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341
  • VELCADE

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the frequency and duration of complete and partial response rates in patients with grade I, II, or III follicular lymphoma or mantle cell lymphoma treated with bortezomib.

SECONDARY OBJECTIVES:

I. Determine the response of minimal residual disease by polymerase chain reaction (PCR) detectable or clonotypic PCR minimal residual disease in bone marrow of patients treated with this regimen.

II. Determine the time to progression and overall survival of patients treated with this regimen.

III. Determine the toxic effects of this regimen in these patients.

OUTLINE: Patients are stratified according to disease type (follicular lymphoma vs mantle cell lymphoma).

Patients receive an infusion of bortezomib over 3-5 seconds once weekly for 4 weeks. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients who achieve at least a partial response lasting at least 6 months may receive retreatment.

Patients are followed every 3 months for 1 year and then every 4 months for 2 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed lymphoproliferative disorder of 1 of the following subtypes:
  • * Relapsed or refractory grade I, II, or III follicular center cell lymphoma

    • Relapsed or refractory mantle cell lymphoma
  • Measurable disease for non-Hodgkin's lymphoma (NHL) only

    • At least 1 unidimensionally measurable lesion
    • At least 2 cm by conventional techniques OR at least 1 cm by spiral CT scan
    • Lymph nodes no greater than 1 cm in short axis considered normal
  • Absolute lymphocytosis greater than 5,000/mm^3 with B-cell phenotype (CD19, 20,or 23 positive) with more than 30% bone marrow lymphocytes for CLL or other leukemic forms of NHL
  • No known brain metastases
  • Performance status - Karnofsky 70-100%
  • At least 3 months
  • See Disease Characteristics
  • Absolute neutrophil count greater than 1,500/mm^3 (500/mm^3 if lymphomatous involvement of bone marrow)
  • Platelet count greater than 50,000/mm^3
  • Bilirubin less than 1.5 times upper limit of normal (ULN)
  • AST and ALT no greater than 2.5 times ULN (4 times ULN in case of liver metastases)
  • Creatinine less than 1.5 times ULN
  • No symptomatic congestive heart failure
  • No New York Heart Association class III or IV heart disease
  • No unstable angina pectoris
  • No cardiac arrhythmia
  • No myocardial infarction within the past 6 months
  • No cerebrovascular accident or transient ischemic attack within the past 6 months
  • No history of orthostatic hypotension
  • No evidence of acute ischemia or significant conduction abnormality (left anterior hemiblock in the presence of right bundle branch block or second or third degree atrioventricular blocks) on electrocardiogram
  • No uncontrolled hypertension requiring antihypertensive medication
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Febrile episodes up to 38.5°C allowed if no evidence of active infection
  • No other uncontrolled concurrent illness
  • No known or active HIV infection
  • No ongoing or active infection
  • No psychiatric illness or social situation that would preclude study entry
  • At least 3 months since prior monoclonal antibody therapy (e.g., rituximab)
  • No more than 3 prior regimens of conventional cytotoxic chemotherapy
  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
  • At least 1 week since prior steroid therapy
  • At least 4 weeks since prior radiotherapy and recovered
  • At least 4 weeks since prior major surgery
  • No other concurrent investigational agents
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00023764

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Investigators
Principal Investigator: John Gerecitano Memorial Sloan-Kettering Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00023764     History of Changes
Other Study ID Numbers: NCI-2012-01406, NCI-2012-01406, UNMC-03903, MSKCC-01049, NCI-2795, CDR0000068860, CWRU-MSKCC-1Y02, 01-049, 2795, P30CA008748, U01CA062502, N01CM62206
Study First Received: September 13, 2001
Results First Received: October 23, 2013
Last Updated: April 25, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma, Follicular
Lymphoma, Mantle-Cell
Lymphoproliferative Disorders
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bortezomib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 19, 2014