Clinical trial NCT00656812: Rituximab Plus 2CdA in Patients With Advanced or Relapsed Mucosa Associated Lymphoid Tissue (MALT) Lymphoma
Official title: Phase II Trial of Rituximab Plus 2CdA in Patients With Advanced or Relapsed Lymphoma of the Mucosa Associated Lymphoid Tissue (MALT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma of Mucosa-Associated Lymphoid Tissue
Keywords: advanced MALT lymphoma
Rituximab
2CdA
chemotherapy
immunotherapy
Lead sponsor: Arbeitsgemeinschaft medikamentoese Tumortherapie
Sponsor class: OTHER
Collaborators: name: Hoffmann-La Roche
name: Lipomed
First posted: 2008-04-11
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this trial is to evaluate whether a Rituximab plus 2 CdA combination therapy is effective and safe in the treatment of patients with advanced or relapsed lymphoma of the mucosa associated lymphoid tissue (MALT).

Detailed description: Currently, there is no chemotherapeutic standard treatment for patients with MALT lymphoma either presenting with disseminated disease or with relapsing/refractory disease following local treatment (including radiation) or eradication of HP. Various compounds have been tested, including alkylating agents such as cyclophosphamide or chlorambucil, the nucleoside analog cladribine (2CdA), as well as combination regimens including CHOP or MCP (mitoxantrone, chlorambucil, prednisone), but only limited data exists from prospective trials. Thus, trials to evaluate the potential of new compounds in patients with advanced MALT lymphoma are not only justified, but seem warranted.

While systemic approaches were until recently thought to be justified only in patients with disseminated disease, emerging data suggest that also patients with localized disease potentially amenable to radiation may benefit from systemic treatment. This has been demonstrated for ocular adnexal MALT lymphoma and recently also for gastric MALT lymphoma in a randomized fashion, where application of chemotherapy resulted in a significantly longer time to relapse as opposed to surgery or radiation without impairing overall survival.

Both 2CdA and rituximab have been demonstrated as active single agents in MALT lymphoma with mild toxicity profiles and no data on combination therapy with rituximab plus chemotherapy in MALT lymphoma have been published to date. This study will therefore evaluate the efficacy and safety of Rituximab plus 2CdA in patients with advanced or relapsed lymphoma of the mucose associated lymphoid tissue.

Eligibility criteria: Inclusion Criteria:

* Histologically proven diagnosis of MALT lymphoma of any localization
* Disseminated disease upon diagnosis in case of gastric lymphoma or first or greater relapse after local therapy (including gastrectomy or surgery), prior chemotherapy or HP-eradication. In addition, also patients with localized gastric lymphoma judged refractory to HP-eradication by a minimum follow-up of 12 months after successful HP-eradication can be included in the study.
* Measurable disease
* ECOG performance status of 0,1 or 2
* Age at least 18 years
* Life expectancy of at least 3 months
* Adequate cardiac, renal and liver function tests (LVEF \> 50%, serum creatinine \< 2.5 mg/dl, ALAT or ASAT \< 2.5 x upper limit of normal range (ULN), alkaline phosphatase \< 2.5 x ULN, serum bilirubin \< 2.0 mg/dl)
* Patient must be willing and able to comply with the protocol for the entire study duration
* Women of child-bearing potential must have a negative pregnancy test and must agree to use effective contraception for the entire treatment period
* Patient's written informed consent

Exclusion Criteria:

* Lymphoma histology other than MALT lymphoma or MALT lymphoma transforming to diffuse large cell lymphoma ("high grade lymphoma")
* Use of any investigational agent 30 days prior to inclusion
* 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
* Clinically significant cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 6 months
* Inadequate hematological status at baseline prior to study entry: Dependency on red blood cell and/or platelet transfusions, ANC (absolute neutrophile count (segmented + bands) \<1.0 x 109/L
* Patients with active opportunistic infections
* Pregnant or breast feeding women

Primary outcomes:
measure: Response rate
timeFrame: After 2, 4 and 6 cycles of therapy
Secondary outcomes:
measure: Progression-free survival and relapse-free survival
timeFrame: Duration of study
measure: Occurrence of adverse events
timeFrame: Duration of study
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Universitätsklinikum Graz
city: Innsbruck
country: Austria
facility: Universitaetsklinik Innsbruck/ Klinik für Innere Medizin
city: Linz
country: Austria
facility: Krankenhaus der Stadt Linz
city: Salzburg
country: Austria
facility: Universitaetsklinik f. Innere Medizin III
city: Vienna
country: Austria
facility: AKH Wien / Universitaetsklinik fuer Innere Medizin I
Study officials:
affiliation: AKH Wien / Universitaetsklinik fuer Innere Medizin I
name: Markus Raderer, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: