Clinical study of the combination of acalabrutinib with tafasitamab in previously treated patients with marginal zone lymphoma (MZL)

Austria, Italy, Switzerland (ICTRP)

ICTRP Trial ID
NCT04646395 (ICTRP)

Official title (approved by ethics committee)
Phase II trial of acalabrutinib in combination with tafasitamab in patients with previously treated marginal zone lymphomas (MZL) (BASEC)

Academic title
Phase II Trial of Acalabrutinib in Combination With Tafasitamab in Patients With Previously Treated Marginal Zone Lymphomas (MZL) (ICTRP)

Public title
Study of Acalabrutinib and Tafasitamab in MZL Patients (ICTRP)

Disease under investigation
Marginal Zone Lymphoma (ICTRP)

Intervention under investigation
Drug: Tafasitamab;Drug: Acalabrutinib (ICTRP)

Type of trial
Interventional (ICTRP)

Trial design
Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)

Inclusion/Exclusion criteria
Gender: All
Maximum age: N/A
Minimum age: 18 Years
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 with no deterioration over the previous 2 weeks
prior to registration .

- 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:

- History of prior malignancy that could affect compliance with the protocol or
interpretation of results, except for the following:

1. Curatively treated basal cell carcinoma or squamous cell carcinoma of the skin
or carcinoma in situ of the cervix or carcinoma in situ of the prostate at any
time prior to study,

2. Other cancers not specified above that have been curatively treated by surgery
and/or radiation therapy from which patient is disease-free for =3 years
without further treatment.

- 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

- History of or ongoing confirmed central nervous system (CNS) lymphoma

- Patients who received any IMP within 30 days or 5 half-lives (whichever is shorter)
before the first dose of the study IMP

- Pregnant or breastfeeding women

- Patients who received a live virus vaccination within 28 days of the first IMP dose (ICTRP)

not available

Primary and secondary end points
Complete Response (CR) Rate as best response to treatment (ICTRP)

Number of treatment emergent adverse events (AE);Overall Response Rate (ORR);Progression Free Survival (PFS);Duration of response (DoR);Overall Survival (OS) (ICTRP)

Registration date
17.11.2020 (ICTRP)

Incorporation of the first participant
not available

Secondary sponsors
not available

Additional contacts
Anastasios Stathis, MD;Davide Rossi, MD;Emanuele Zucca, MD, Oncology Institute of Southern Switzerland - Bellinzona, Switzerland,Oncology Institute of Southern Switzerland - Bellinzona, CH,Oncology Institute of Southern Switzerland - Bellinzona, CH (ICTRP)

Secondary trial IDs
2019-004396-38, IELSG49 (ICTRP)

Results-Individual Participant Data (IPD)
not available

Further information on the trial
https://clinicaltrials.gov/ct2/show/NCT04646395 (ICTRP)