JOURNAL ONKOLOGIE – STUDIE
Study of Acalabrutinib and Tafasitamab in MZL Patients
Indikation (Clinical Trials):
Lymphoma, Lymphoma, B-Cell, Marginal Zone
International Extranodal Lymphoma Study Group (IELSG)
Oncology Institute of Southern Switzerland - Bellinzona, Switzerland
Oncology Institute of Southern Switzerland - Bellinzona, CH
Oncology Institute of Southern Switzerland - Bellinzona, CH
Phone: +41 91 811
Phone (ext.): 9040
E-Mail: firstname.lastname@example.org» Kontaktdaten anzeigen
Studienlocations (3 von 3)
Markus Raderer, MD
E-Mail: email@example.com» Ansprechpartner anzeigenAUSL Ravenna U.O. Ematologia
Monica Tani, MD
E-Mail: firstname.lastname@example.org» Ansprechpartner anzeigenOncology Institute of Southern Switzerland
Anastasios Sthatis, MD
E-Mail: Anastasios.Stathis@eoc.ch» Ansprechpartner anzeigen
Marginal zone B cell lymphomas (MZLs) comprise three distinct entities: extranodal MZL (EMZL)
of mucosa-associated lymphoid tissue type (MALT) lymphoma, splenic MZL (SMZL) and nodal MZL
Together they represent approximately 5%-15% of all non-Hodgkin lymphomas.
MZL are in general indolent lymphomas with relatively low risk of transformation. The
available treatment options can lead to responses but disease recurrence is often observed.
For patients with MZL and recurrent disease following initial treatment, currently there is
no established standard therapy and new treatment options and treatment combinations are
The proposed trial will evaluate the safety and efficacy of the anti-CD19 monoclonal antibody
tafasitamab in combination with the BTK inhibitor acalabrutinib. The B-lymphocyte, lineage
specific surface antigen CD19 is broadly and homogeneously expressed in MZLs. This makes CD19
an attractive target for the treatment of MZL patients, in particular those who failed a
previous rituximab-containing regimen.
On the other hand, genetic and immunogenetic data point to B-cell receptor signalling as a
key oncogenic pathway of MZLs. The activity of single agent ibrutinib in MZLs is an in vivo
proof that MZLs are addicted of BTK-driven signalling and that the BCR pathway is a
vulnerability of these lymphomas.
The safety profile of the anti CD19 monoclonal antibody tafasitamab and of the BTK inhibitor
acalabrutinib indicate the possibility that their combination can be developed without major
overlapping side effects.
The proposed trial is a prospective multicenter trial combining tafasitamab and acalabrutinib
in patients with MZL (including EMZL, SMZL and NMZL) with disease refractory to or in first
or greater relapse after prior systemic therapy.
- Ability to understand and willingness to sign a written informed consent
- Histologically confirmed diagnosis of MZL.
- Disease refractory to or in first or greater relapse after prior systemic therapy.
- In need of treatment disease satisfying the following criteria:
- EMZL: symptomatic lymphoma or with other treatment indications (overt
progression, deep invasion, bulky disease, impending organ damage, patient
preference), symptomatic disseminated disease, contraindications to RT, failure
after antibiotics or after local therapy,
- SMZL: presence of progressive or symptomatic splenomegaly and/ or any progressive
- NMZL: B symptoms, deterioration of peripheral blood counts due to lymphoma
infiltration of the bone marrow, rapid enlargement of lymph nodes or compression
of vital organs by bulky disease.
- Measurable or non-measurable lesions where the response is nevertheless evaluable by
non-imaging means (e.g., gastric or bone marrow infiltrations).
- Ann Arbor Stage I-IV.
- ECOG performance status of 0, 1 or 2.
- Age ≥ 18 years.
- Absolute neutrophil count (ANC) ≥ 1.000/mm3 and platelets ≥ 100.000/mm3, unless these
abnormalities are related to bone marrow infiltration or to hypersplenism.
- Adequate hepatic function, renal function and coagulation parameters
- Women with childbearing potential who are using highly effective contraception, are
not pregnant or lactating and agree not to become pregnant during trial treatment and
for at least 3 months after the last IMP dose.
- Men who agree not to father a child during trial treatment and for at least 3 months
after the last IMP dose.
- Patient able and willing to swallow trial drugs as whole capsule
- Patients with a prior malignancy and treated with curative intention, unless all
treatments of that malignancy were completed at least 2 years before registration and
the patient has no evidence of disease at registration. Less than 2 years is
acceptable for malignancies with low-risk of recurrence and/or no late recurrence.
- Major surgery and any systemic anti-cancer treatment within 3 weeks prior to
- Prior exposure to a BTK inhibitor or CD19-targeted therapy.
- Steroid therapy for anti-neoplastic intent.
- Severe or uncontrolled cardiovascular disease
- History of cerebrovascular accident or intracranial hemorrhage within 6 months prior
to registration and known bleeding disorders
- Patients with a history of confirmed progressive multifocal leukoencephalopathy (PML).
- Concomitant diseases that require anticoagulant therapy with warfarin or
phenoprocoumon or other vitamin K antagonists and patients treated with dual
anti-platelet therapy. Patients being treated with factor Xa inhibitors (e.g.
rivaroxaban, apixaban, edoxaban), direct thrombin inhibitors (e.g. dabigatran) LMWH,
or single anti-platelets agents (e.g. aspirin, clopidogrel) can be included, but must
be properly informed about the potential risk of bleeding.
- Malabsorption syndrome or other condition that precludes enteral route of
- Active human immunodeficiency virus (HIV) or active chronic hepatitis C or hepatitis B
virus infection or any uncontrolled active systemic infection requiring intravenous
(iv) antimicrobial treatment.
- Active, uncontrolled autoimmune phenomenon (autoimmune hemolytic anemia or immune.
thrombocytopenia) requiring steroid therapy with > 20 mg daily of prednisone dose or
- Known hypersensitivity to trial drugs or to any component of the trial drugs.
- Concomitant treatment with strong CYP3A inducers or inhibitors
- Treatment with proton pump inhibitors. Subjects receiving proton pump inhibitors who
switch to antacids are eligible for enrollment to this study.
- Other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that in the opinion of the investigator may increase the risk associated
with trial participation or IMPs administration or may interfere with the
interpretation of trial results and/or would make the patient inappropriate for
enrolment into this trial.
- Concurrent participation in another therapeutic clinical trial
1. Complete Response (CR) Rate as best response to treatment (Time Frame - Between 11 - 13 weeks after treatment start, at the end of cycles 6, 12, 18, 24 (each cycle is 28 days)):
defined according to the international Revised Response Criteria for Malignant Lymphoma (Cheson et al 2014). For patients with SMZL, response is defined according to Matutes et al. 2008 and for patients with gastric lymphomas, histological response is evaluated according to GELA scoring system (Copie-Bergman et al 2003).
1. Number of treatment emergent adverse events (AE) (Time Frame - From the time of informed consent signature until 28 days after treatment discontinuation or until resolution of all treatment-related AEs, whichever occurs later.):
Analysis of type and severity of Adverse Events according to CTCAE v5.0 and relationship to study treatment
2. Overall Response Rate (ORR) (Time Frame - Between 11 - 13 weeks after treatment start, at the end of cycles 6, 12, 18, 24 (each cycle is 28 days)):
ORR will be defined as sum of PR plus CR defined according to the revised response criteria for malignant lymphomas (Cheson et al 2014), to the GELA Histological Grading System for gastric EMZL and the Matutes criteria for SMZL.
3. Progression Free Survival (PFS) (Time Frame - From the date of treatment start to the date of progression or the date of death for any cause until 3 years from last treatment dose):
PFS will be computed from the first IMP dose to date of disease progression or date of death for any reason or censored at the date of the last follow-up visit, whichever occurs earlier
4. Duration of response (DoR) (Time Frame - From the date of the first documented response to the date of disease progression or relapse or death until 3 years from last treatment dose):
DOR will be define as the time between the first documented response to therapy and subsequent disease progression or relapse or death according to the international Revised Response Criteria for Malignant Lymphoma (Cheson et al 2014).
5. Overall Survival (OS) (Time Frame - From the date of treatment start to the date of death for any cause until 3 years from last treatment dose):
Overall survival (OS) will be computed from the first IMP dose to the date of death for any reason or censored at the date of the last contact, whichever occurs earlier
- Tafasitamab (MOR00208):
200 mg powder for reconstitution with 5 ml water for injection
- Acalabrutinib (Calquence):
100 mg hard gelatin capsules