A study to evaluate acalabrutinib, in combination with the R-CHOP standard of care, for previously untreated mantle cell lymphoma in Spain.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Astrazeneca Farmaceutica Spain S.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

4 Sep 2025 → ongoing

Decision date (initial)

2025-06-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

AstraZeneca Farmaceútica Spain S.A.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To assess the efficacy in terms of treatment response to acalabrutinib, in combination with the R-CHOP standard of care, in subjects with previously untreated MCL.

Secondary objectives 2

1. To further assess the efficacy of acalabrutinib, in combination with the R-CHOP standard of care, in subjects with previously untreated MCL.
2. To assess the safety and tolerability profile of acalabrutinib, in combination with the R-CHOP standard of care, in subjects with previously untreated MCL.

Conditions and MedDRA coding

mantle cell lymphoma (MCL)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Adult (aged ≥18 years) men or women.
2. WOCBP who are sexually active must use highly effective methods of contraception during the study treatment and for 12 months after the last dose of rituximab or cyclophosphamide, 6 months after the last dose of doxorubicin, 30 days after the last dose of vincristine, and 2 days after the last dose of acalabrutinib, whichever is the longerst. NOTE: Female participants should be stable on the chosen method of contraception for a minimum of 3 months before entering a trial.
3. Male patients should use barrier contraception (ie, condoms) from the time of screening until 12 months after the last dose of rituximab or cyclophosphamide, 6 months after the last dose of doxorubicin, 30 days after the last dose of vincristine, and 2 days after the last dose of acalabrutinib , whichever is longest. Male patients wishing to father children in the future should be advised to arrange for the freezing of sperm prior to the start of study treatment. NOTE: Female partners should be advised to use accepted contraception during their partner’s study treatment and for 12 months after the last dose of rituximab or cyclophosphamide, 6 months after the last dose of doxorubicin, 30 days after the last dose of vincristine, and 2 days after the last dose of acalabrutinib, whichever is longest.
4. Pathologically confirmed MCL, with documentation of chromosome translocation t(11;14)(q13;q32) and/or overexpression of cyclin D1 in association with other relevant markers
5. MCL requiring treatment and for which no prior systemic anticancer therapies have been received
6. Presence of radiologically measurable lymphadenopathy, splenomegaly and/or extranodal lymphoid malignancy
7. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
8. Men who are sexually active and can beget children must agree to use highly effective forms of contraception during the study treatment and for 12 months after the last dose of rituximab or cyclophosphamide, 6 months after the last dose of doxorubicin, 30 days after the last dose of vincristine, and 2 days after the last dose of acalabrutinib, whichever is longest.
9. Men must agree to refrain from sperm donation during the study treatment and for 12 months after the last dose of rituximab or cyclophosphamide, 6 months after the last dose of doxorubicin, 30 days after the last dose of vincristine, and 2 days after the last dose of acalabrutinib, whichever is longest
10. Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing tablets without difficulty
11. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local patient privacy regulations).
12. Unsuitable for autologous stem cell transplantation

Exclusion criteria 27

1. History of prior malignancy except for the following: a. Malignancy treated with curative intent and with no evidence of active disease present for more than 2 years before screening and felt to be at low risk for recurrence by treating physician. Note: Provided they meet other eligibility criteria, subjects who are receiving hormonal therapy alone are allowed to enroll on study. b. Adequately treated lentigo maligna melanoma without current evidence of disease or adequately controlled nonmelanomatous skin cancer. c. Adequately treated carcinoma in situ without current evidence of disease.
2. Prothrombin time/international normalized ratio (INR) or activated partial thromboplastin time (aPTT) (in the absence of a lupus anticoagulant) >2.0 x ULN. Exception: Subjects receiving a vitamin K antagonist are excluded; however, those receiving other anticoagulant therapy who have a higher INR/aPTT may be permitted to enroll to this study after discussion with the medical monitor
3. Malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach, extensive small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.
4. Uncontrolled active systemic fungal, bacterial, viral, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment), or intravenous anti-infective treatment within 2 weeks before first dose of study drug.
5. Known history of infection with human immunodeficiency virus (HIV).
6. Ongoing immunosuppressive therapy, including systemic (e.g., IV or oral) corticosteroids within 2 weeks before the first dose of study drug. Note: Subjects may use topical or inhaled corticosteroids or low-dose steroids (≤20 mg prednisone equivalent/day for ≤2 weeks) as a therapy for comorbid conditions and/or pre-phase treatment up to 100 mg/day or equivalent (for a maximum of 10 days prior to beginning study treatment) in participants with bulky disease, systemic symptoms, compressive disease, impaired liver function or cytopenias due to lymphoma, or rapidly progressing adenopathies. During study participation, subjects will receive corticosteroids as part of the R-CHOP regimen according to institution standards. Subjects may also receive systemic (e.g., IV or oral) corticosteroids as needed for treatment-emergent comorbid conditions.
7. Known history of anaphylaxis or hypersensitivity to any study drug, or any of their components.
8. Serologic status reflecting active hepatitis B or C infection. a. Subjects who are anti-HBc positive and who are surface antigen negative will need to have a negative polymerase chain reaction (PCR) result before the first dose of study drug. Those who are HbsAg positive or hepatitis B PCR positive will be excluded. b. Subjects who are hepatitis C antibody positive will need to have a negative PCR result before the first dose of study drug. Those who are hepatitis C PCR positive will be excluded.
9. Received a live virus vaccination within 28 days of first dose of study drug.
10. History of stroke or intracranial hemorrhage within 6 months of first dose of study drug.
11. History of bleeding diathesis (e.g., hemophilia or von Willebrand disease).
12. Subjects for whom the goal of therapy is tumor debulking before stem cell transplant
13. Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before first dose of study drug.
14. Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon) within 7 days of first dose of study drug.
15. Requires treatment with a strong CYP3A inhibitor/inducer
16. Concurrent participation in another therapeutic clinical trial.
17. Active cytomegalovirus (CMV) infection (active viremia as evidenced by positive PCR result for CMV DNA).
18. History of confirmed progressive multifocal leukoencephalopathy (PML).
19. Any history of central nervous system (CNS) lymphoma or leptomeningeal disease
20. Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP).
21. Major surgical procedure within 28 days before first dose of study drug. Note: If a subject had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug.
22. Significant cardiovascular disease such as uncontrolled or untreated symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of first dose of study drug, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification at screening. Exception: Subjects with controlled, asymptomatic atrial fibrillation during screening are allowed to enroll on study.
23. Absolute neutrophil count (ANC) <1.0 x 109/L or platelet count <75 x 109/L; for subjects with disease involvement in the bone marrow, ANC <0.75 x 109/L or platelet count <50 x 109/L. Subjects will only be considered eligible if peripheral blood counts can be maintained independent of growth factors or transfusions during the screening period.
24. Total bilirubin >1.5 x upper limit normal (ULN) unless other reason known (e.g. Gilbert Syndrome, or due to lymphoma involvement); or aspartate aminotransferase (AST) or alanine transaminase (ALT) >2.5 x ULN.
25. Estimated creatinine clearance of <30 mL/min, calculated using the formula of Cockcroft and Gault [(140-age) • mass (kg)/(72 • creatinine mg/dL) • multiply by 0.85 if female].
26. Subjects who are deemed by the treating physician to be unfit to tolerate the R-CHOP regimen.
27. Pregnant or breastfeeding women.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Investigator-assessed best ORR (CR+PR) as per the Lugano Classification for NHL. Timeframe: 1 year

Secondary endpoints 8

1. TTR, defined as the time from the date of acalabrutinib start to the first investigator-assessed CR or PR per the Lugano Classification for NHL. Measure of interest: median TTR.
2. DoR, defined as the time from the first documentation of investigator-assessed CR or PR to disease progression per the Lugano Classification for NHL or death from any cause in the absence of disease progression. Measure of interest: 30-month DoR
3. PFS, defined as the time from the date of acalabrutinib start to investigator-assessed disease progression as per the Lugano Classification for NHL or death from any cause, whichever occurs first. Measure of interest: 30-month PFS.
4. OS, defined as the time from the date of acalabrutinib start to the date of death from any cause. Measure of interest: 30-month OS
5. Describe the number and percentage of patients with each MedDRA coded and CTCAE graded adverse (AEs) and serious adverse events (SAEs).
6. Incidence of AEs of clinical interest for acalabrutinib.
7. Incidence of grade ≥3 AEs.
8. Incidence of AEs leading to acalabrutinib dose modification, temporary interruption or permanent discontinuation.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Astrazeneca Farmaceutica Spain S.A.

Sponsor organisation

Astrazeneca Farmaceutica Spain S.A.

Address

Calle Del Puerto De Somport 21-23, Poligono Industrial Carretera De Burgos Poligono Industrial Carretera De Burgos

City

Madrid

Postcode

28050

Country

Spain

Scientific contact point

Organisation

Astrazeneca Farmaceutica Spain S.A.

Contact name

Jorge Castro García

Public contact point

Organisation

Astrazeneca Farmaceutica Spain S.A.

Contact name

AstraZeneca Clinical Study Information Center

Third parties 2

Locations

1 EU/EEA country · 21 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 10 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