Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid TissuePhase 1NCT00068315

Bortezomib and Fludarabine With or Without Rituximab in Treating Patients With Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia

A Phase 1 study testing bortezomib, fludarabine phosphate and rituximab in people with Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue and Hematopoietic/Lymphoid Cancer, run by National Cancer Institute (NCI) at 7 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Hematopoietic/Lymphoid Cancer, Nodal Marginal Zone B-cell Lymphoma
What is being tested?: bortezomib, fludarabine phosphate and rituximab
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 18 participants
Where: 7 sitesUnited States
Study dates: Jul 2003to Dec 2008
Phase: Phase 1

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Diagnosis of chronic lymphocytic leukemia (CLL) OR indolent non-Hodgkin's lymphoma (NHL) of any of the following subtypes:
Follicular lymphoma:
Grade I follicular small cleaved cell;
Grade II follicular mixed cell;
Grade II follicular large cell;
Diffuse small cleaved cell;

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Small lymphocytic lymphoma;
Lymphoplasmacytic lymphoma (Waldenstrom's macroglobulinemia)
AND
Extranodal marginal zone B-cell lymphoma (mucosa-associated lymphoid tissue [MALT] lymphoma);
Nodal marginal zone B-cell lymphoma (monocytoid B-cell lymphoma);
Splenic marginal zone lymphoma (splenic lymphoma with villous lymphocytes);
Mantle cell lymphoma:
No blastic phase mantle cell lymphoma
Relapsed or refractory, progressive disease:
First, second, or third relapse
Measurable disease, meeting 1 of the following criteria:
At least 1 unidimensionally measurable lesion at least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan (for NHL patients);
OR:
Lymphocytosis > 50,000/mm3 OR evidence of progressive bone marrow infiltration failure (e.g., hemoglobin 10 g/dL) OR thrombocytopenia (i.e., platelet count < 100,000/mm3) with > 30% infiltration of bone marrow by leukemia (for CLL patients)
No measurable lymphadenopathy (for CLL and Waldenstrom's macroglobulinemia patients)
No evidence of CNS lymphoma
Performance status:
ECOG 0-2
Life expectancy:
More than 12 weeks
No history of uncontrolled orthostatic hypotension
No symptomatic congestive heart failure
No unstable angina pectoris
No cardiac arrhythmia
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
HIV negative
No uncontrolled concurrent illness
No grade 2 or greater neuropathy
No history of allergy or anaphylaxis to mannitol, bortezomib, fludarabine, or boron
No ongoing or active infection
No psychiatric illness or social situation that would preclude study compliance
At least 4 weeks since prior monoclonal antibody (MoAB) therapy:
Patients who have received MoAB therapy within the past 3 months must have documented disease progression since receiving this therapy
No prior allogeneic stem cell transplantation
More than 4 weeks since prior chemotherapy
Prior fludarabine allowed
At least 1 week since prior steroids
At least 3 months since prior radio-immunotherapy
More than 4 weeks since prior radiotherapy
No prior bortezomib
Absolute neutrophil count at least 1,500/mm3
Platelet count at least 75,000/mm3 (greater than 50,000/mm3 if lymphomatous bone marrow involvement is present)
Bilirubin no greater than 2.0 mg/dL
AST/ALT no greater than 4 times normal
Creatinine clearance greater than 40 mL/min
No other concurrent investigational agents or treatments for the malignancy
No brain metastases
OR:
Quantitation of IgM paraprotein (for Waldenstrom's macroglobulinemia patients)

Who cannot join

None listed.

Trial locations and contacts

7 sites in 1 country.

City, postcode or hospital

7 sites in 1 country

United States7 sites

Mercy Medical Center
Canton, Ohio, 44708
Case Western Reserve University
Cleveland, Ohio, 44106
Seidman Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
Cleveland, Ohio, 44106
Southwest General Health Center Ireland Cancer Center
Middleburg Heights, Ohio, 44130
UHHS-Chagrin Highlands Medical Center
Orange, Ohio, 44122
University Suburban Medical Center
South Euclid, Ohio, 44121
UHHS-Westlake Medical Center
Westlake, Ohio, 44145

Other trials in United States

About this study

Official title: A Phase I Trial of PS-341 and Fludarabine for Relapsed and Refractory Indolent Non-Hodgkin's Lymphoma and Chronic Lymphocytic Leukemia

This phase I trial is studying the side effects and best dose of bortezomib when given together with fludarabine with or without rituximab in treating patients with relapsed or refractory indolent non-Hodgkin's lymphoma or chronic lymphocytic leukemia. Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Drugs used in chemotherapy, such as fludarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving bortezomib together with fludarabine with or without rituximab may kill more cancer cells.

Read the detailed description

OBJECTIVES:

Determine the safety and toxicity of bortezomib and fludarabine with or without rituximab in patients with relapsed or refractory indolent non-Hodgkin's lymphoma or chronic lymphocytic leukemia.

II. Determine the maximum tolerated dose of bortezomib in combination with fludarabine in these patients.

III. Determine the biological effect of this regimen on apoptotic markers, cell cycle kinase inhibitors, and DNA repair in these patients.

OUTLINE: This is a multicenter, dose-escalation study of bortezomib.

Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11 and fludarabine IV over 30 minutes on days 1-3 or 1-5. Patients may also receive rituximab IV over 1 hour on day 1. Treatment repeats every 3 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Conditions: Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Hematopoietic/Lymphoid Cancer, Nodal Marginal Zone B-cell Lymphoma, Recurrent Adult Diffuse Small Cleaved Cell Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma
Being tested: bortezomib, fludarabine phosphate, rituximab
Medical subject headings: Hematologic Neoplasms, Lymphoma, B-Cell, Marginal Zone, Lymphoma, Non-Hodgkin, Lymphoma, Follicular, Lymphoma, Mantle-Cell, Leukemia, Lymphocytic, Chronic, B-Cell, Waldenstrom Macroglobulinemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

bortezomibDrug
Also called LDP 341, MLN341, VELCADE
Given IV
fludarabine phosphateDrug
Also called 2-F-ara-AMP, Beneflur, Fludara
Given IV
rituximabBiological
Also called IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8
Given IV

Study groups in NCT00068315
Study group	Role	What they receive
Treatment (bortezomib, fludarabine, rituximab)	Experimental	Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11 and fludarabine IV over 30 minutes on days 1-3 or 1-5. Patients may also receive rituximab IV over 1 hour on day 1. Treatment repeats every 3 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Receives: Drug: bortezomib; Drug: fludarabine phosphate; Biological: rituximab

What is being measured

The primary outcome is the main question the study is designed to answer.

Maximum tolerated dose (MTD) assessed by Common Toxicity Criteria version 2.0
Measured: 3 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2003Dec 2008

First posted11 Sep 2003 (estimated)
Study startJul 2003
Primary completionDec 2008

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid TissueStudies of the same condition, open and under way.
More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 18 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00068315
Sponsor's protocol ID: NCI-2009-00044
Other IDs: NCI-2009-00044, ICC 3402, CDR0000321394, ICC 3402, 6126, U01CA062502
Status last verified: Sep 2013
First submitted: 10 Sep 2003
Last updated: 30 Sep 2013
Results posted: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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