Clinical study of the combination of acalabrutinib with tafasitamab in previously treated patients with marginal zone lymphoma (MZL)
Zusammenfassung der Studie
The study aims to determine the efficacy of the combination of two medications, tafasitamab and acalabrutinib, in patients with recurrent or refractory marginal zone lymphoma. The study includes a total of 24 treatment cycles, each cycle lasting 28 days, for a total of approximately two years of treatment. Patients will receive: • Acalabrutinib in capsules daily for 24 cycles • Tafasitamab intravenously on days 1, 8, 15, and 22 for the first 3 cycles Thereafter, patients will continue treatment until cycle 24 with tafasitamab intravenously on day 1. At the end of treatment, there will be an observation period of up to 3 years.
(BASEC)
Untersuchte Intervention
Before the start of treatment, the following examinations will be performed:
•Medical visit and assessment of ECOG performance status
•Concomitant pharmacological assessment
•Electrocardiogram
•Hematology (complete blood count and differential)
•Pregnancy test for women of childbearing age
•Laboratory tests (Na, K, Ca, P, albumin, uric acid, creatinine, LDH, ASAT, ALAT, bilirubin, beta-2-microglobulin, PT/INR, aPTT, Coombs test, serum glucose)
•Human immunodeficiency virus (HIV), HBV and HCV serology; HBV-DNA in HBcAb+ patients and HCV-RNA in HCV Ab+ patients
•IgG, IgM, IgA (urinary and serum immunofixation if a monoclonal component is suspected) and serum protein electrophoresis
•Flow cytometry of peripheral blood in NMZL and SMZL
•CT scan of the neck, chest, abdomen, and pelvis or FDG-PET/CT scan
•Endoscopic investigations with biopsies and magnetic resonance imaging, if clinically appropriate
•Biopsy and bone marrow aspiration (BM)
•Circulating tumor DNA (ctDNA)
During participation in the study, the following examinations will be performed for disease reassessment:
From cycle 1 to cycle 3:
Day 1 of each cycle
• Pregnancy test for women of childbearing age (on day 1 of cycle 1, the pregnancy test may be omitted if performed ≤ 7 days prior)
Day 1 of cycle 3
• HBV-DNA in HBcAb+ patients at screening
Day 1, 8, 15, 22
• Clinical examination, including vital signs and assessment of ECOG performance status
• Concomitant pharmacological assessment
• Electrocardiogram, if clinically indicated
• Hematology (complete blood count and differential)
Day 1, 15
• Laboratory analyses (Na, K, Ca, P, albumin, uric acid, creatinine, LDH, ASAT, ALAT, bilirubin) (on day 1 of cycle 1, the laboratory analysis may be omitted if performed ≤ 7 days prior)
During weeks 11 - 13
• Flow cytometry of peripheral blood, in case of complete remission, to confirm the response in NMZL and SMZL (only if positive at screening)
• CT scan of the neck, chest, abdomen, and pelvis or FDG-PET/CT scan
• Endoscopic investigations with biopsies and magnetic resonance imaging, if clinically appropriate
• Biopsy and bone marrow aspiration (BM), if positive at screening or clinically appropriate
• ctDNA1
From cycle 4 to cycle 6:
Day 1 of each cycle
• Pregnancy test for women of childbearing age
Day 1 of cycle 6
• HBV-DNA in HBcAb+ patients at screening
Day 1, 15
• Clinical examination, including vital signs and assessment of ECOG performance status
• Concomitant pharmacological assessment
• Electrocardiogram, if clinically indicated
• Hematology (complete blood count and differential)
• Laboratory analyses (Na, K, Ca, P, albumin, uric acid, creatinine, LDH, ASAT, ALAT, bilirubin)
At the end of cycle 6:
• Flow cytometry of peripheral blood, in case of complete remission, to confirm the response in NMZL and SMZL (only if positive at screening)
• CT scan of the neck, chest, abdomen, and pelvis or FDG-PET/CT scan
• Endoscopic investigations with biopsies and magnetic resonance imaging, if clinically appropriate
• Biopsy and bone marrow aspiration (BM), if positive at screening or clinically appropriate
From cycle 7 to cycle 24:
Day 1 of each cycle
• Pregnancy test for women of childbearing age
• Clinical examination, including vital signs and assessment of ECOG performance status
• Concomitant pharmacological assessment
• Hematology (complete blood count and differential)
• Laboratory analyses (Na, K, Ca, P, albumin, uric acid, creatinine, LDH, ASAT, ALAT, bilirubin)
Day 1 of cycles 9, 12, 15, 18, 21, 24
• HBV-DNA in patients positive for HBsAg or HBcAb at pre-treatment
At the end of cycles 12, 18:
• Free light chains
• Flow cytometry of peripheral blood
• CT scan of the neck, chest, abdomen, and pelvis or FDG-PET/CT scan
• Endoscopic investigations with biopsies and magnetic resonance imaging, if clinically appropriate
• Biopsy and bone marrow aspiration (BM)
At the end of cycle 24 or upon treatment discontinuation (PD or any reason other than PD):
• Clinical examination, including vital signs and assessment of ECOG performance status
• Concomitant pharmacological assessment
• Electrocardiogram, if clinically indicated
• Hematology (complete blood count and differential)
• Laboratory analyses (Na, K, Ca, P, albumin, uric acid, creatinine, LDH, ASAT, ALAT, bilirubin, beta-2-microglobulin)
• Serum IgG, IgM, IgA (urinary and serum immunofixation if a monoclonal component is suspected) and serum protein electrophoresis
• Flow cytometry of peripheral blood, in case of complete remission at the end of cycle 24, to confirm the response in NMZL and SMZL (only if positive at screening)
• CT scan of the neck, chest, abdomen, and pelvis or FDG-PET/CT scan
• Endoscopic investigations with biopsies and magnetic resonance imaging, if clinically appropriate
• Biopsy and bone marrow aspiration (BM), if positive at screening or clinically appropriate
• ctDNA
(BASEC)
Untersuchte Krankheit(en)
Patients with B-cell marginal zone lymphoma (MZL), previously treated
(BASEC)
1) Patients previously treated with histological confirmation of diagnosis of marginal zone lymphoma (MZL) who have had a relapse of disease or have not responded to prior therapies, including: -Patients with extranodal marginal zone lymphoma -Patients with splenic marginal zone lymphoma -Patients with nodal marginal zone lymphoma 2) Measurable or evaluable disease 3) Adequate bone marrow, renal, and hepatic function (BASEC)
Ausschlusskriterien
1) Previous exposure to a BTK inhibitor or targeted therapy for CD19 2) Severe or uncontrolled cardiovascular disease, history of cerebrovascular accident or intracranial hemorrhage within the 6 months prior to registration, known bleeding disorders, history of confirmed progressive multifocal leukoencephalopathy, concomitant diseases requiring anticoagulation therapy 3) Active infection with active human immunodeficiency virus (HIV) or chronic hepatitis C or hepatitis B infection 4) Pregnancy or breastfeeding (BASEC)
Studienstandort
Bellinzona
(BASEC)
Sponsor
International Extranodal Lymphoma Study Group (IELSG)
(BASEC)
Kontakt für weitere Auskünfte zur Studie
Kontaktperson Schweiz
International Extranodal Lymphoma Study Group (IELSG)
+41 (0)91 811 90 40
ielsg@cluttereoc.chInternational Extranodal Lymphoma Study Group (IELSG)
(BASEC)
Allgemeine Auskünfte
Oncology Institute of Southern Switzerland - Bellinzona, Switzerland,Oncology Institute of Southern Switzerland - Bellinzona, CH,Oncology Institute of Southern Switzerland - Bellinzona, CH
(ICTRP)
Wissenschaftliche Auskünfte
Oncology Institute of Southern Switzerland - Bellinzona, Switzerland,Oncology Institute of Southern Switzerland - Bellinzona, CH,Oncology Institute of Southern Switzerland - Bellinzona, CH
(ICTRP)
Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)
Ethikkommission Tessin
(BASEC)
Datum der Bewilligung durch die Ethikkommission
07.06.2021
(BASEC)
ICTRP Studien-ID
NCT04646395 (ICTRP)
Offizieller Titel (Genehmigt von der Ethikkommission)
Phase II trial of acalabrutinib in combination with tafasitamab in patients with previously treated marginal zone lymphomas (MZL) (BASEC)
Wissenschaftlicher Titel
Phase II Trial of Acalabrutinib in Combination With Tafasitamab in Patients With Previously Treated Marginal Zone Lymphomas (MZL) (ICTRP)
Öffentlicher Titel
Study of Acalabrutinib and Tafasitamab in MZL Patients (ICTRP)
Untersuchte Krankheit(en)
Marginal Zone Lymphoma (ICTRP)
Untersuchte Intervention
Drug: Tafasitamab;Drug: Acalabrutinib (ICTRP)
Studientyp
Interventional (ICTRP)
Studiendesign
Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)
Ein-/Ausschlusskriterien
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)
nicht verfügbar
Primäre und sekundäre Endpunkte
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)
Registrierungsdatum
17.11.2020 (ICTRP)
Einschluss des ersten Teilnehmers
nicht verfügbar
Sekundäre Sponsoren
nicht verfügbar
Weitere Kontakte
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)
Sekundäre IDs
2019-004396-38, IELSG49 (ICTRP)
Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar
Weitere Informationen zur Studie
https://clinicaltrials.gov/ct2/show/NCT04646395 (ICTRP)
Ergebnisse der Studie
Zusammenfassung der Ergebnisse
nicht verfügbar
Link zu den Ergebnissen im Primärregister
nicht verfügbar