Lymphoma of the Mucosa Associated Lymphoid Tissue (MALT)
Conditions
Keywords
MALT Lymphoma, Lenalidomide, Rituximab, AGMT
Brief summary
This is an open label, phase II study to evaluate the capacity of Rituximab (Mabthera®) plus Lenalidomide (Revlimid®) to induce objective responses in patients with Mucosa Associated Lymphoid Tissue (MALT) lymphoma presenting with measurable disease.
Interventions
Rituximab 375 mg/m² i.v. day 1 Lenalidomide 20 mg p.o. daily for 21 days Cycles should be repeated every 28 days. Restaging should be performed after three cycles. In case of at least stable disease, patients should receive another three courses of therapy. Patients with documented CR after 6 courses will stop therapy/study, while patients with PR or SD will be given another two cycles for a maximum of 8 cycles.
Sponsors
Arbeitsgemeinschaft medikamentoese Tumortherapie
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
selected: * Histologically verified diagnosis if MALT lymphoma of any localization * Measurable disease upon diagnosis or first or greater relapse after local therapy, prior chemotherapy orHP-eradication. In addition, also in patients with gastric MALT-lymphoma judged refractory to HP-eradication by a minimum follow-up of 12 months after successfulHP-eradication will be included in the study. Patients with gastric MALT lymphoma and no evidence of HP-infection may be enrolled immediately * Ann Arbor Stage I-IV * In case of prior treatment with Rituximab, the presence of CD20 on lymphoma cells must have been demonstrated before inclusion in the trial. * ECOG performance status of 0,1 or 2 * Patient must be able to take aspirin daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin
Exclusion criteria
selected: * Lymphoma histology other than MALT lymphoma or MALT lymphoma with a diffuse large cell lymphoma (high grade lymphoma) - component * Use of any investigational agent within 28 days prior to initiation of treatment with lenalidomide * History of malignancy other than squamous cell carcinoma, basal cell carcinoma of the skin or carcinoma in situ of the cervix within the last 5 years * Major surgery, other than diagnostic surgery, within the last 4 weeks * Evidence of CNS involvement * A history of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant and adversely affecting compliance to study drugs * Severe peripheral polyneuropathy * Clinically significant cardiac disease or myocardial infarction within the last 6 months * Known hypersensitivity to thalidomide or lenalidomide or rituximab
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Responses in Patients With MALT Lymphoma Presenting With Measureable Disease | 40 weeks | The primary objective of this Phase II study is to evaluate the proportion of patients responding to Lenalidomide and Rituximab. In case of a response rate of \< 40%, the combination is rejected as ineffective, while an active combination is defined at a minimum response rate of 60% based of findings with rituximab and lenalidomide mono-therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number and Severity of Adverse Events | From treatment start until 28 days after last study treatment; expected study duration 24 months | Safety of Rituximab (Mabthera®) plus Lenalidomide (Revlimid®) in this patient population |
| Influence of Rituximab Plus Lenalidomide on T-cell Subsets | Day 1, 14 and 28 of cycle 1 and day 1 of cycle 5 | T-cell subsets will be evaluated from EDTA blood in a central lab |
Countries
Austria
Participant flow
Recruitment details
50 patients were enrolled at 4 sites in Austria. First patient in was 06-Jun-2012; Last patient in was 26-May-2014.
Pre-assignment details
2 patients were withdrawn before first response evaluation and were replaced. 2 patients withdrew their consents prior to study treatment and did not experience AEs to other study procedures. These 2 patients were therefore excluded from intent-to-treat (ITT) efficacy assessments, safety assessments and listing of baseline characteristics.
Participants by arm
| Arm | Count |
|---|---|
| Rituximab and Lenalidomide Rituximab was administered on day 1 of each cycle in a dose of 375 mg/m² (28 day cycle). Dose of lenalidomide for investigation is 20 mg/day, orally on days 1 to 21 followed by 7 days pause.Restaging should be performed after three cycles. In case of at least stable disease, patients should receive another three courses of therapy. Patients with documented CR after 6 courses stopped therapy/study, while patients with PR or SD were given another two cycles for a maximum of 8 cycles. | 48 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Lack of Efficacy | 2 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 7 |
Baseline characteristics
| Characteristic | Rituximab and Lenalidomide |
|---|---|
| Age, Continuous | 65 years |
| Sex: Female, Male Female | 29 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 47 / 48 |
| serious Total, serious adverse events | 18 / 48 |
Outcome results
Primary
Objective Responses in Patients With MALT Lymphoma Presenting With Measureable Disease
The primary objective of this Phase II study is to evaluate the proportion of patients responding to Lenalidomide and Rituximab. In case of a response rate of \< 40%, the combination is rejected as ineffective, while an active combination is defined at a minimum response rate of 60% based of findings with rituximab and lenalidomide mono-therapy.
Time frame: 40 weeks
Population: 48 patients were included into safety assessment, two of them received treatment but no efficacy assessment was available. Therefore, these two patients were neither included into Intention-to-treat nor Per-protocol efficacy analysis.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Rituximab and Lenalidomide | Objective Responses in Patients With MALT Lymphoma Presenting With Measureable Disease | CR | 25 Participants |
| Rituximab and Lenalidomide | Objective Responses in Patients With MALT Lymphoma Presenting With Measureable Disease | PR or SD | 20 Participants |
| Rituximab and Lenalidomide | Objective Responses in Patients With MALT Lymphoma Presenting With Measureable Disease | PD | 1 Participants |
Secondary
Influence of Rituximab Plus Lenalidomide on T-cell Subsets
T-cell subsets will be evaluated from EDTA blood in a central lab
Time frame: Day 1, 14 and 28 of cycle 1 and day 1 of cycle 5
Secondary
Number and Severity of Adverse Events
Safety of Rituximab (Mabthera®) plus Lenalidomide (Revlimid®) in this patient population
Time frame: From treatment start until 28 days after last study treatment; expected study duration 24 months