An Open-label, Phase 1b/2 Study of Acalabrutinib Alone or in Combination Therapy in Subjects with B-cell Non-Hodgkin Lymphoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Acerta Pharma B.V.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

16 Sep 2020 → ongoing

Decision date (initial)

2024-10-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Acerta Pharma BV

External identifiers

EU CT number

2023-509350-63-00

EudraCT number

2019-000111-84

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Pharmacodynamic, Efficacy

PART 2: To characterize the activity of acalabrutinib alone or in combination with rituximab in subjects with R/R MZL, as measured by ORR

Secondary objectives 2

1. PART 2: To characterize the safety of acalabrutinib alone or in combination with rituximab in subjects with R/R MZL
2. PART 2: To evaluate the activity of acalabrutinib alone or in combination with rituximab in subjects with R/R MZL, as measured by DOR, PFS, and OS

Conditions and MedDRA coding

Relapsed/Refractory marginal zone lymphoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Men and women ≥18 years of age.
2. Histologically confirmed MZL including splenic, nodal, and extranodal sub-types
3. Previous therapy: a. Cohort 1: Previously received 1 or more lines of systemic therapy including at least 1 CD20-directed regimen (either as monotherapy or as chemoimmunotherapy for MZL) with documented failure to achieve at least PR, or documented disease progression after the most recent treatment regimen. b. Cohort 2: Previously received 1 or more lines of therapy including at least 1 prior systemic therapy for MZL or radiation therapy with documented failure to achieve at least PR, or document disease progression after the most recent treatment regimen.
4. Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of ≥1 lesion that measures ≥2.0 cm in the longest dimension and ≥1.0 cm in the longest perpendicular dimension as assessed by CT scan).
5. ECOG performance status of ≤2.
6. Ability to understand the purpose and risks of the study and provide signed and dated informed consent

Exclusion criteria 19

1. Prior malignancy (other than indolent B-cell NHL), except for adequately treated basal cell or squamous cell skin cancer, in situ cancer, or other cancer from which the subject has been disease free for ≥2 years.
2. Known medically apparent CNS lymphoma or leptomeningeal disease.
3. Known evidence of transformation to another aggressive lymphoma.
4. A life-threatening illness, medical condition, or organ system dysfunction which, in the investigator’s opinion, could compromise the subject’s safety, interfere with the absorption or metabolism of acalabrutinib, or put the study outcomes at undue risk.
5. Known history of a bleeding diathesis (e.g., hemophilia, von Willebrand disease).
6. Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or corrected QT interval using Fridericia formula (QTcF) >480 msec.
7. Prior exposure to a BCR inhibitor (e.g., BTK, or SYK inhibitors).
8. Ongoing immunosuppressive therapy, including systemic or enteric corticosteroids for treatment or other conditions within 1 week before the first dose of study drug.
9. 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.
10. Known history of infection with HIV.
11. Serologic status reflecting active hepatitis B or C infection.
12. History of allogeneic stem cell (or organ) transplantation.
13. History of stroke or intracranial hemorrhage within 6 months before the first dose of acalabrutinib.
14. Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonist (e.g., phenprocoumon) within 7 days of first dose of study drug.
15. ANC <1.0 × 109/L or platelet count <100 × 109/L. For subjects with documented disease involvement in the bone marrow, ANC <0.50 × 109/L or platelet count <30 × 109/L.
16. Creatinine >1.5 × institutional ULN; total bilirubin >1.5 × ULN; and AST or ALT >2.5 × ULN.
17. Breastfeeding or pregnant.
18. Received any chemotherapy, external beam radiation therapy, anticancer antibodies, or investigational drug within 30 days before first dose of study drug.
19. History of or ongoing progressive multifocal leukoencephalopathy (PML).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Efficacy: Investigator-assessed ORR according to the Lugano classification for NHL.

Secondary endpoints 2

1. Monitoring and recording AEs and SAEs; hematology, serum chemistry, serum Ig, and T/B/NK-cell count results; vital signs measurements; ECOG; and concomitant medications.
2. Investigator-assessed DOR, PFS, and OS according to the Lugano classification for NHL

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Acerta Pharma B.V.

Sponsor organisation

Acerta Pharma B.V.

Address

Kloosterstraat 9

City

Oss

Postcode

5349 AB

Country

Netherlands

Scientific contact point

Organisation

Acerta Pharma B.V.

Contact name

Global Clinical Lead

Public contact point

Organisation

Acerta Pharma B.V.

Contact name

Global Clinical Lead

Third parties 2

Locations

1 EU/EEA country · 2 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 6 files

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

Application history

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