JOURNAL ONKOLOGIE – STUDIE

Study of Acalabrutinib and Tafasitamab in MZL Patients

Studien-Informationen Einschlusskriterien Studien-Rationale Geprüfte Regime

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NCT-Nummer:
NCT04646395

Studienbeginn:
März 2021

Letztes Update:
30.11.2020

Wirkstoff:
Tafasitamab, Acalabrutinib

Indikation (Clinical Trials):
Lymphoma, Lymphoma, B-Cell, Marginal Zone

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
International Extranodal Lymphoma Study Group (IELSG)

Collaborator:
-

Studienleiter

Anastasios Stathis, MD
Study Chair
Oncology Institute of Southern Switzerland - Bellinzona, Switzerland

Davide Rossi, MD
Study Chair
Oncology Institute of Southern Switzerland - Bellinzona, CH

Emanuele Zucca, MD
Study Chair
Oncology Institute of Southern Switzerland - Bellinzona, CH

Kontakt

Emanuele Zucca, MD
Kontakt:
Phone: +41 91 811
Phone (ext.): 9040
E-Mail: ielsg@c.ch» Kontaktdaten anzeigen

Studienlocations (3 von 3)

University of Wien
1190 Wien
Austria» Google-Maps
Ansprechpartner:
Markus Raderer, MD
E-Mail: markus.raderer@meduniwien.ac.at» Ansprechpartner anzeigen

AUSL Ravenna U.O. Ematologia
48121 Ravenna
Italy» Google-Maps
Ansprechpartner:
Monica Tani, MD
E-Mail: monica.tani@auslromagna.it» Ansprechpartner anzeigen

Oncology Institute of Southern Switzerland
6500 Bellinzona
Switzerland» Google-Maps
Ansprechpartner:
Anastasios Sthatis, MD
E-Mail: Anastasios.Stathis@eoc.ch» Ansprechpartner anzeigen

Studien-Informationen

Detailed Description:

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

(NMZL).

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

needed.

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.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- 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

cytopaenias,

- 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

Exclusion Criteria:

- 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

registration.

- 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

administration.

- 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

equivalent.

- 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

Studien-Rationale

Primary outcome:

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).

Secondary outcome:

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

Geprüfte Regime

Tafasitamab (MOR00208):
200 mg powder for reconstitution with 5 ml water for injection
Acalabrutinib (Calquence):
100 mg hard gelatin capsules

Quelle: ClinicalTrials.gov