Clinical study of acalabrutinib and tafasitamab in previously treated marginal zone lymphoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Association International Extranodal Lymphoma Study Group (IELSG)

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

7 Oct 2021 → ongoing

Decision date (initial)

2024-07-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Astra Zeneca AG · Incyte Bioseciences International Sarl

External identifiers

EU CT number

2024-514122-23-00

EudraCT number

2019-004396-38

ClinicalTrials.gov

NCT04646395

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To determine the efficacy of tafasitamab in combination with acalabrutinib in patients with relapsed or refractory MZL

Secondary objectives 2

1. To evaluate the safety profile of tafasitamab in combination with acalabrutinib in patients with relapsed or refractory MZL
2. To further evaluate the efficacy of tafasitamab in combination with acalabrutinib in patients with relapsed or refractory MZL

Conditions and MedDRA coding

Marginal Zone Lymphomas refractory to or in first or greater relapse after prior systemic therapy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Ability to understand and willingness to sign a written informed consent
2. Histologically confirmed diagnosis of MZL
3. Disease refractory to or in first or greater relapse after prior systemic therapy
4. 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 radiotherapy (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
5. Measurable or non-measurable lesions where the response is nevertheless evaluable by non-imaging means (e.g., gastric or bone marrow infiltrations)
6. Ann Arbor Stage I-IV (Appendix A)
7. ECOG performance status of 0, 1 or 2 with no deterioration over the previous 2 weeks prior to registration
8. Age ≥ 18 years
9. Absolute neutrophil count (ANC) ≥ 1.000/mm3 and platelets ≥ 100.000/mm3, unless these abnormalities are related to bone marrow infiltration or to hypersplenism
10. Adequate kidney and liver function
11. Adequate coagulation parameters
12. 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
13. Men who agree not to father a child during trial treatment and for at least 3 months after the last IMP dose
14. Patient able and willing to swallow trial drugs as whole capsule

Exclusion criteria 20

1. History of prior malignancy that could affect compliance with the protocol or interpretation of results, except for the following: a. 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, b. 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
2. Any uncontrolled active systemic infection requiring intravenous (iv) antimicrobial treatment
3. Active human immunodeficiency virus (HIV) or active chronic hepatitis C or hepatitis B virus infection. Patients positive for hepatitis B core antibody (HBcAb) will be eligible if they are negative for HBV-DNA
4. Active, uncontrolled autoimmune phenomenon (autoimmune hemolytic anemia or immune thrombocytopenia) requiring steroid therapy with > 20 mg daily of prednisone dose or equivalent
5. Major surgery and any systemic anti-cancer treatment within 3 weeks prior to registration. If patients had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first IMP dose
6. Prior exposure to a BTK inhibitor or CD19-targeted therapy
7. Steroid therapy for anti-neoplastic intent
8. Severe or uncontrolled cardiovascular diseases
9. History of cerebrovascular accident or intracranial hemorrhage within 6 months prior to registration and known bleeding disorders (e.g., von Willebrand's disease or hemophilia)
10. Patients with a history of confirmed progressive multifocal leukoencephalopathy (PML)
11. Concomitant diseases that require anticoagulant therapy with warfarin or phenoprocoumon or other vitamin K antagonists and patients treated with dual anti-platelet therapy
12. Malabsorption syndrome or other condition that precludes enteral route of administration
13. Known hypersensitivity to trial drugs or to any component of the trial drugs
14. Concomitant treatment with strong CYP3A inducers or inhibitors
15. Treatment with proton pump inhibitors. Subjects receiving proton pump inhibitors who switch to antacids are eligible for enrollment to this study
16. Concurrent participation in another therapeutic clinical trial
17. History of or ongoing confirmed central nervous system (CNS) lymphoma
18. Patients who received any IMP within 30 days or 5 half-lives (whichever is shorter) before the first dose of the study IMP
19. Patients who received a live virus vaccination within 28 days of the first IMP dose
20. Pregnant or breastfeeding women

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Complete response rate (CR) as best response to treatment, defined according to the international Revised Response Criteria for Malignant Lymphoma . 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

Secondary endpoints 5

1. Adverse events type and severity according to CTCAE v5.0 and relationship to study treatment
2. Overall response rate (ORR)
3. Progression free survival (PFS)
4. Duration of response (DOR)
5. Overall survival (OS)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Association International Extranodal Lymphoma Study Group (IELSG)

Sponsor organisation

Association International Extranodal Lymphoma Study Group (IELSG)

Address

Via Vincenzo Vela 6

City

Bellinzona

Postcode

6500

Country

Switzerland

Scientific contact point

Organisation

Association International Extranodal Lymphoma Study Group (IELSG)

Contact name

IELSG Operations Office

Public contact point

Organisation

Association International Extranodal Lymphoma Study Group (IELSG)

Contact name

IELSG Operations Office

Locations

2 EU/EEA countries · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 3 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications