Rituximab Plus 2CdA in Patients With Advanced or Relapsed Mucosa Associated Lymphoid Tissue (MALT) Lymphoma

Sponsor

Arbeitsgemeinschaft medikamentoese Tumortherapie (Other)

Overall Status

Completed

CT.gov ID

NCT00656812

Collaborator

Hoffmann-La Roche (Industry), Lipomed (Industry)

Enrollment

Locations

Arm

Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Lymphoma of Mucosa-Associated Lymphoid Tissue	Drug: Rituximab Drug: 2-CdA	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase II Trial of Rituximab Plus 2CdA in Patients With Advanced or Relapsed Lymphoma of the Mucosa Associated Lymphoid Tissue (MALT)

Study Start Date :

May 1, 2008

Actual Primary Completion Date :

Sep 1, 2011

Actual Study Completion Date :

Sep 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Arm Combination therapy Rituximab plus 2CdA	Drug: Rituximab 375 mg/m2 on day 1 of a 21-day treatment cycle Other Names: MabThera Drug: 2-CdA 0.1 mg/kg s.c. on days 1 - 4 of a 21-day treatment cycle Other Names: Litak

Arm

Intervention/Treatment

Experimental: Treatment Arm

Combination therapy Rituximab plus 2CdA

Drug: Rituximab

375 mg/m2 on day 1 of a 21-day treatment cycle

Other Names:

MabThera

Drug: 2-CdA

0.1 mg/kg s.c. on days 1 - 4 of a 21-day treatment cycle

Other Names:

Litak

Outcome Measures

Primary Outcome Measures

Response rate [After 2, 4 and 6 cycles of therapy]

Secondary Outcome Measures

Progression-free survival and relapse-free survival [Duration of study]
Occurrence of adverse events [Duration of study]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Universitätsklinikum Graz	Graz	Austria	A-8036
2	Universitaetsklinik Innsbruck/ Klinik für Innere Medizin	Innsbruck	Austria	A-6020
3	Krankenhaus der Stadt Linz	Linz	Austria	A-4020
4	Universitaetsklinik f. Innere Medizin III	Salzburg	Austria	A-5020
5	AKH Wien / Universitaetsklinik fuer Innere Medizin I	Vienna	Austria	A-1090