MALIBU Trial - Combination of Ibrutinib and Rituximab in Untreated Marginal Zone Lymphomas (MALIBU)

STATUS

Recruiting
End date

Jun 15, 2027
participants needed

175
sponsor

International Extranodal Lymphoma Study Group (IELSG)

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Updated on 14 May 2022

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remission

rituximab

antiviral

cytopenia

marginal zone lymphoma

lymphadenopathy

gastric malt lymphoma

splenic marginal zone lymphoma

Summary

Single-arm, phase II clinical trial of patients with Extranodal Marginal Zone Lymphoma (EMZL). It is planned to recruit 130 patients.

Additional patients with Splenic Marginal Zone Lymphoma (SMZL), up to 30, and Nodal Marginal Zone Lymphoma (NMZL), up to 15, will be included in the trial in order to preliminary explore the clinical activity and safety of the combination treatment proposed.

The study primary endpoints will be analysed on the EMZL population. Outcome of patients with SMZL and NMZL will be analysed and reported separately

Description

Marginal zone lymphomas (MZL) represent a group of indolent B-cell lymphomas that arises from marginal zone B-cells in extranodal tissues, such as spleen and mucosa associated lymphoid tissues, and more rarely also in nodal tissues. MZL comprises 5 to 17% of all non-Hodgkin lymphomas (NHL) in adults. The 2016 World Health Organization (WHO) recognized three separate subtypes of MZL according to their primary localization, namely the:

extranodal MZL (EMZL) of mucosa-associated lymphoid tissue (MALT), also known as MALT lymphoma
splenic MZL (SMZL)
nodal MZL (NMZL). These three subtypes are distinct disease entities that are classified together because they all seem to originate from post germinal centre marginal zone B-cells.

MALIBU trial is a prospective multicenter trial combining rituximab and ibrutinib in front-line for patients with MZL, including EMZL, SMZL and NMZL Aim of the study is to assess the safety and efficacy of the combination of rituximab and ibrutinib in EMZL patients and to explore its activity in SMZL and NMZL as exploratory subset.

Details

Condition	Marginal Zone Lymphoma, Nodal Marginal Zone Lymphoma, Splenic Marginal Zone Lymphoma
Treatment	Rituximab, Ibrutinib
Clinical Study Identifier	NCT03697512
Sponsor	International Extranodal Lymphoma Study Group (IELSG)
Last Modified on	14 May 2022

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Eligibility		Yes	No	Not Sure
Inclusion Criteria
	Chemotherapy and immunotherapy-naïve, symptomatic and in need of treatment patients, with
	histologically proven CD20-positive MZL, not eligible for local therapy, including
	EMZL (MALT Lymphoma) patients with MALT- IPI score 1-2 in need of systemic therapy
	Either de novo or relapsed following local therapy (including surgery, radiotherapy
	and antibiotics for H. pylori-positive gastric lymphoma) arisen at any extranodal site
	with MALT-international prognostic index (IPI) score 1-2 at the time of study entry
	H. pylori-negative cases, either de novo (non pretreated) or at relapse following
	1.The following patients with gastric MALT Lymphoma can be entered
	local therapy (i.e., surgery, radiotherapy or antibiotics)
	H. pylori-positive cases at diagnosis, who either first line antibiotics or
	further local treatment (surgery or radiotherapy), including patients with
	clinical (endoscopic) and histological evidence of disease progression at
	any time post H. pylori eradication
	clinical (endoscopic) and histological relapse (without H. pylori
	re-infection), after a remission patients
	persistent (stable) lymphoma at ≥ 1 year post H. pylori eradication. 1.2
	Similar consideration may be applied to patients with ocular adnexal
	bulky progressive or painful splenomegaly
	lymphoma treated with antibiotics
	SMZL patients in need of therapy. Either de novo or relapsed following local therapy
	one of the following symptomatic/progressive cytopenias
	[including surgery and antiviral therapy for Hepatitis C virus (HCV)]. Patient must
	Hgb < 10 g/dL
	have a symptomatic disease requiring treatment and be not eligible for splenectomy or
	not willing to undergo splenectomy
	1. Patients with SMZL can be entered if any of the following criteria is present
	enlarged lymph nodes or involvement of extranodal sites with or without
	cytopenias , i.e. involvement of ≥3 nodal sites, each with a diameter of ≥3 cm
	Any nodal tumor mass with a diameter of ≥7 cm (GELG criteria, as adopted in
	follicular lymphoma)
	Measurable or evaluable disease
	ANC < 1000/μL
	PLT< 80 000/μL whatever the reason (autoimmune or hypersplenism or bone
	marrow infiltration)
	Life expectancy of at least 1 year
	2. Splenectomised patients with rapidly raising lymphocyte counts, lymphadenopathy
	ECOG Performance status 0-2
	or involvement of extranodal sites can be entered
	Adequate bone marrow, kidney and liver function
	3. SMZL with concomitant HCV infection who have not responded to or are relapsed
	after antiviral therapy can be entered
	NMZL patients in need of therapy Either, de novo presenting with disseminated disease
	or relapsed after local radiotherapy or following antiviral therapy for HCV. Localized
	nodal MZL is not eligible
	Ann Arbor II-IV. Stage I disease may be eligible only if not candidate to local
	therapy (surgery or radiotherapy)
	Age ≥ 18
	For women of childbearing potential only: negative serum pregnancy test done
	within 7 days prior to study drugs administration or within 14 days if with a
	confirmatory urine pregnancy test within 7 days prior to the first study drugs
	administration
	Fertile male or female patients of childbearing potential and their partners must
	use higly effective contraception methods during the study and for at least 12
	months after the last dose of subcutaneous rituximab. In case hormonal methods of
	birth control is used a barrier method must be added
	Ability to understand and the willingness to sign a written informed consent
	document
Exclusion Criteria
	Known CNS involvement of MZL
	Major surgery within 4 weeks prior to registration
	History of stroke or intracranial bleeding within 6 months
	Known bleeding diathesis (eg, von Willebrand's disease) or hemophilia
	Concurrent use of warfarin of other vitamin K antagonists
	Vaccinated with live, attenuated vaccines within 4 weeks prior to randomization
	Positive test results for chronic HBV infection (defined as positive HBsAg serology)
	HIV infection or immunodeficiency
	Active, severe infections
	Pregnancy or breastfeeding
	Any type of lymphoma other than MZL (including MZL with histologic transformation to
	high-grade lymphoma)
	Localized (stage IE and IIE) MALT lymphoma, for example gastric, ocular and cutaneous
	lymphoma, that may benefit from local therapy only (surgery or radiotherapy)
	Any previous systemic treatment with immunotherapy or chemotherapy or with BTK
	inhibitors
	Concurrent use of strong cytochrome P450 (CYP)3A4/5 inhibitors (see
	<http://medicine.iupui.edu/clinpharm/ddis/clinical-table/>)
	Any life-threatening illness, medical condition, or organ system dysfunction which, in
	the investigator's opinion, could compromise the subject's safety, interfere with the
	absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue
	risk
	International normalized ratio (INR) or prothrombin time (PT) ≥1.5 ULN. Partial
	thromboplastin time (PTT) or activated PTT (aPTT) ≥1.5 ULN unless due to lupus
	anticoagulant
	Clinically significant hypersensitivity (e.g., anaphylactic or anaphylactoid reactions
	to the compound of ibrutinib and/or rituximab themselves or to the excipients in their
	formulation)
	Patients with occult or prior HBV infection (defined as negative HBsAg and positive
	total HBcAb) may be included if HBV DNA is undetectable, provided that they are
	willing to undergo monthly DNA testing and taking specific antiviral prophylaxis
	according to local policy. Patients who have protective titers of hepatitis B surface
	antibody (HBsAb) after vaccination are eligible
	Positive test results for hepatitis C. Patients positive for HCV antibody are eligible
	only if PCR is negative for HCV RNA
	Clinically significant cardiovascular diseases such as uncontrolled or symptomatic
	arrhythmias, congestive heart failure, or myocardial infarction within 6 months of
	screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by
	the New York Heart Association Functional Classification
	Any serious medical or psychiatric illness likely to interfere with participation in
	this clinical study
	Prior history of malignancies other than MZL within 3 years,with the exception of
	adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer
	Current enrolment or participation in another therapeutic clinical trial within 28
	days prior to treatment start

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MALIBU Trial - Combination of Ibrutinib and Rituximab in Untreated Marginal Zone Lymphomas (MALIBU)