Lymphoma, Non-Hodgkin, MALT Lymphoma
Conditions
Keywords
Fludarabine, Rituximab, Marginal Zone Lymphoma, MALT lymphoma
Brief 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.
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%.
Interventions
DRUGFludarabine
DRUGRituximab
Sponsors
Beth Israel Deaconess Medical Center
Massachusetts General Hospital
University of Rochester
Genentech, Inc.
Biogen
Dana-Farber Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | Assessed after three- and six-cycles of therapy. | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 3.1-Year Progression-Free Survival | Assessed after 3- and 6-cycles of therapy, every 6 months for 2 years and then annually up to 4 years | 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). |
| 3.1-Year Overall Survival | Assessed after 3- and 6-cycles of therapy, every 6 months for 2 years and then annually up to 4 years | 3.1-year overall survival is the probability of patients remaining alive 3.1 years from study entry. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Fludarabine
Rituximab | 26 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 9 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Trt for Pre-Exist Second Primary | 1 |
Baseline characteristics
| Characteristic | Fludarabine and Rituximab |
|---|---|
| Age, Continuous | 63.7 years |
| Histology MALT | 8 participants |
| Histology Nodal MZL | 14 participants |
| Histology Splenic MZL | 4 participants |
| Region of Enrollment United States | 26 participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 25 / 26 |
| serious Total, serious adverse events | 20 / 26 |
Outcome results
Primary
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.
Population: The analysis dataset is comprised of all treated patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fludarabine and Rituximab | Objective Response Rate | .85 proportion of patients |
Secondary
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
Population: The analysis dataset is comprised of all treated patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fludarabine and Rituximab | 3.1-Year Overall Survival | 0.874 probability |
Secondary
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
Population: The analysis dataset is comprised of all treated patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fludarabine and Rituximab | 3.1-Year Progression-Free Survival | 0.795 probability |
Post Hoc
Delayed 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.
Population: The analysis dataset is comprised of all treated patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fludarabine and Rituximab | Delayed Bone Marrow Toxicity Rate | 0.154 proportion of patients |
Post Hoc
Delayed 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.
Population: The analysis dataset is comprised of all treated patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fludarabine and Rituximab | Delayed Pneumonia Toxicity Rate | 0.115 proportion of patients |