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CompletedNCT00117156Updated Aug 1, 2016Results posted

Fludarabine and Rituximab for the Treatment of Marginal Zone Non-Hodgkin's Lymphoma

A Phase 2 interventional study of Fludarabine and Rituximab in Lymphoma, Non-Hodgkin and MALT Lymphoma, sponsored by Dana-Farber Cancer Institute. Completed at 4 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2016-08-01.

Sponsored by Dana-Farber Cancer Institute · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
26
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

The purpose of this study is to determine the effectiveness of six cycles of concurrent fludarabine and rituximab in patients with mucosa-associated lymphoid tissue (MALT) lymphoma, marginal zone lymphoma (MZL) or CD5-, CD10-, CD20+ low-grade B cell lymphomas.

Read the detailed description

Objectives:

Primary

- To estimate the objective response rate.

Secondary

  • To assess the safety.
  • To describe the progression-free survival at one year.
  • To examine the association between clonal cytogenetic abnormalities identified by FISH, and the objective response rate as well as the progression-free survival at one year.

Target enrollment was 30 eligible patients. An 80% objective response rate at 1 month restaging after 6 cycles was considered as evidence of activity in this patient population while 60% was not considered activity. If at least 22 patients achieved objective response the treatment would be considered promising. With 30 eligible patients, the probability of observing this was 0.87 assuming a true rate of 80% and 0.09 assuming a true rate of 60%.

02

Conditions studied

  • Lymphoma, Non-Hodgkin
  • MALT Lymphoma

Keywords

  • Fludarabine
  • Rituximab
  • Marginal Zone Lymphoma
  • MALT lymphoma
03

In context

Lymphoma, Non-Hodgkin

2,043 studies on the registry are indexed under Lymphoma, Non-Hodgkin; 309 are open to participants now.

This study's enrollment of 26 is below the median of 40 across 1,744 interventional studies indexed under Lymphoma, Non-Hodgkin.

Browse Lymphoma, Non-Hodgkin studies →

Lead sponsor

Dana-Farber Cancer Institute is the lead sponsor of 832 studies on the registry; 122 are open to participants now.

Of its 113 completed or terminated interventional studies of FDA-regulated products, 77 (68%) have results posted.

Browse Dana-Farber Cancer Institute studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Histologically confirmed, newly diagnosed or relapsed MALT, marginal zone lymphoma, or low-grade B cell lymphoproliferative disorder which is CD5-, CD10- and CD20+
  • Pathology must be reviewed at Brigham \& Women's Hospital, Massachusetts General Hospital, or the University of Rochester James P. Wilmot Cancer Center prior to enrollment
  • Documentation of CD20+ status
  • Must not be a candidate for local radiotherapy with curative intent
  • If gastric MALT, not a candidate for antibiotic therapy with curative intent
  • Patients with leukemic phase marginal zone lymphoma are eligible if their absolute lymphocyte count is >10,000 / µl
  • Prior treatment with rituximab is permitted, if rituximab induced an objective response which persisted for at least 6 months
  • Prior radiotherapy is acceptable
  • Measurable disease
  • ANC: > 1000/mm3
  • Platelets: > 100,000/mm3
  • Hemoglobin: > 7 gm/dL
  • Adequate renal function as indicated by serum creatinine \<= 2 mg/dL.
  • Adequate liver function, as indicated by serum total bilirubin \<= 2 mg/dL.
  • AST or ALT \<3x Upper Limit of Normal unless related to primary disease.
  • Men and women of reproductive potential must agree to use an acceptable method of birth control during study treatment and for six months after completion of study treatment.
  • WHO Performance status \</= 2
  • Subject has provided written informed consent.

Exclusion criteria

Exclusion Criteria:

  • Patients with Waldenstrom's Macroglobulinemia or lymphoplasmacytic lymphoma are excluded
  • History of HIV
  • Active infection
  • Known CNS disease
  • Pregnant (a negative serum pregnancy test should be performed for all women of childbearing potential within 7 days of treatment) or currently lactating women
  • Prior treatment within the last three weeks
  • Prior fludarabine
  • Positive direct antiglobulin test
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
26 participants (actual)

Study arms

  • Experimental
    Fludarabine and Rituximab

    Fludarabine: 25 mg/m2 on days 1-5 of 28 day cycle up to 6 cycles Rituximab: 375 mg/m2 on day 1 of 28 day cycle up to 6 cycles Rituximab dose was split between days 1 and 3 for patients with absolute lymphocyte counts \> 10x10\^9/L Patients received three cycles of therapy followed by re-staging with chest/ abdomen/ pelvic CT scan. Patients with progressive disease discontinued treatment. Patients with stable or responding disease continued therapy for another 3 cycles.

    Drug: Fludarabine · Drug: Rituximab

Interventions

06

What researchers measure

Primary outcomes

  1. Objective Response Rate

    Objective response rate is defined as the proportion of patients who achieve complete remission (CR), complete remission/unconfirmed (CRu) or partial remission (PR) based on Cheson criteria (1999).

    Time frame: Assessed after three- and six-cycles of therapy.

Secondary outcomes

  1. 3.1-Year Progression-Free Survival

    3.1-year progression-free survival is the probability of patients remaining alive and progression-free at 3.1 years from study entry estimated using Kaplan-Meier methods. Disease progression was assessed per Cheson criteria (1999).

    Time frame: Assessed after 3- and 6-cycles of therapy, every 6 months for 2 years and then annually up to 4 years

  2. 3.1-Year Overall Survival

    3.1-year overall survival is the probability of patients remaining alive 3.1 years from study entry.

    Time frame: Assessed after 3- and 6-cycles of therapy, every 6 months for 2 years and then annually up to 4 years

07

Results

Posted Oct 6, 2014

Participant flow

Participant flow — Overall Study
MilestoneFludarabine and Rituximab
Started26
Completed15
Not completed11
Withdrew: Adverse event9
Withdrew: Physician decision1
Withdrew: Trt for pre-exist second primary1

Outcome measures

PrimaryObjective Response Rate

Objective response rate is defined as the proportion of patients who achieve complete remission (CR), complete remission/unconfirmed (CRu) or partial remission (PR) based on Cheson criteria (1999).

Time frame:
Assessed after three- and six-cycles of therapy.
Reported as:
Number · proportion of patients
Objective Response Rate
proportion of patientsFludarabine and Rituximab
Objective Response Rate.85 (.65 to .96)
Secondary3.1-Year Progression-Free Survival

3.1-year progression-free survival is the probability of patients remaining alive and progression-free at 3.1 years from study entry estimated using Kaplan-Meier methods. Disease progression was assessed per Cheson criteria (1999).

Time frame:
Assessed after 3- and 6-cycles of therapy, every 6 months for 2 years and then annually up to 4 years
Reported as:
Number · probability
3.1-Year Progression-Free Survival
probabilityFludarabine and Rituximab
3.1-Year Progression-Free Survival0.795 (0.634 to 0.956)
Secondary3.1-Year Overall Survival

3.1-year overall survival is the probability of patients remaining alive 3.1 years from study entry.

Time frame:
Assessed after 3- and 6-cycles of therapy, every 6 months for 2 years and then annually up to 4 years
Reported as:
Number · probability
3.1-Year Overall Survival
probabilityFludarabine and Rituximab
3.1-Year Overall Survival0.874 (0.74 to .99)
Post-hocDelayed Bone Marrow Toxicity Rate

Delayed bone marrow toxicity rate is the proportion of patients who experienced significant bone marrow toxicity defined as aplastic anemia or myelodysplastic syndromes (MDS) after completing therapy.

Time frame:
Assessed after therapy completion incidentally or at a minimum every 6 months for 2 years and then annually up to 4 years.
Reported as:
Number · proportion of patients
Delayed Bone Marrow Toxicity Rate
proportion of patientsFludarabine and Rituximab
Delayed Bone Marrow Toxicity Rate0.154 (0.043 to 0.349)
Post-hocDelayed Pneumonia Toxicity Rate

Delayed pneumonia toxicity rate is the proportion of patients who experienced significant pneumonia toxicity defined as nocardia or pneumocystis jiroveci after completing therapy.

Time frame:
Assessed after therapy completion incidentally or at a minimum every 6 months for 2 years and then annually up to 4 years.
Reported as:
Number · proportion of patients
Delayed Pneumonia Toxicity Rate
proportion of patientsFludarabine and Rituximab
Delayed Pneumonia Toxicity Rate0.115 (0.024 to 0.301)

Adverse events

Collected over Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Fludarabine and Rituximab—20/26 (76.9%)25/26 (96.2%)
Most frequent serious events
Showing 10 of 13
Most frequent serious events
EventFludarabine and Rituximab
NeutrophilsInvestigations15/26
LeukocytesInvestigations11/26
PlateletsInvestigations5/26
Febrile neutropeniaBlood and lymphatic system disorders2/26
Rash/desquamationSkin and subcutaneous tissue disorders2/26
HemoglobinBlood and lymphatic system disorders1/26
Fever w/o neutropeniaGeneral disorders1/26
Allergic reactionImmune system disorders1/26
AnorexiaMetabolism and nutrition disorders1/26
DehydrationMetabolism and nutrition disorders1/26
Most frequent other events
Showing 10 of 47
Most frequent other events
EventFludarabine and Rituximab
FatigueGeneral disorders16/26
HemoglobinBlood and lymphatic system disorders15/26
NauseaGastrointestinal disorders9/26
LeukocytesInvestigations9/26
PlateletsInvestigations6/26
Diarrhea w/o prior colostomyGastrointestinal disorders5/26
Fever w/o neutropeniaGeneral disorders5/26
Allergic reactionImmune system disorders5/26
NeutrophilsInvestigations4/26
Rigors/chillsGeneral disorders3/26

Baseline characteristics

Age, Continuous
Age, Continuous(years)Fludarabine and Rituximab
Median63.7 (31.4 to 84.0)
Sex: Female, Male
Sex: Female, Male(Participants)Fludarabine and Rituximab
Female16
Male10
Region of Enrollment
Region of Enrollment(participants)Fludarabine and Rituximab
United States26
Histology
Histology(participants)Fludarabine and Rituximab
Nodal MZL14
MALT8
Splenic MZL4
08

Study locations

4 sites
  • Massachusetts General Hospital
    Boston, Massachusetts 02114, United States
  • Beth Israel Deaconess Medical Center
    Boston, Massachusetts 02115, United States
  • Dana-Farber Cancer Institute
    Boston, Massachusetts 02115, United States
  • University of Rochester Cancer Center
    Rochester, New York 14627, United States
09

References and documents

Publications

  • Brown JR, Friedberg JW, Feng Y, Scofield S, Phillips K, Dal Cin P, Joyce R, Takvorian RW, Fisher DC, Fisher RI, Liesveld J, Marquis D, Neuberg D, Freedman AS. A phase 2 study of concurrent fludarabine and rituximab for the treatment of marginal zone lymphomas. Br J Haematol. 2009 Jun;145(6):741-8. doi: 10.1111/j.1365-2141.2009.07677.x. Epub 2009 Mar 30. PubMed 19344412 ↗
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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 1, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00117156
Lead sponsor
Dana-Farber Cancer Institute
Collaborators
Beth Israel Deaconess Medical Center, Massachusetts General Hospital, University of Rochester, Genentech, Inc., Biogen
Responsible party
Jennifer R. Brown, MD, PhD (Assistant Professor of Medicine, Dana-Farber Cancer Institute) — Principal investigator
First posted
Jul 4, 2005
Start date
Dec 2003
Primary completion
Oct 2008
Completion
Jan 2012
Results posted
Oct 6, 2014
Last update
Aug 1, 2016

Study contacts

Jennifer R. Brown, MD, PhD
principal investigator · Dana-Farber Cancer Institute

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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