A Combination of Acalabrutinib with R-CHOP in Subjects with previously untreated non-GCB DLBCL

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

23 Nov 2020 → ongoing

Decision date (initial)

2024-05-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca UK

External identifiers

EU CT number

2023-509358-72-00

EudraCT number

2019-001755-39

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy, Pharmacokinetic

To evaluate if the addition of acalabrutinib to RCHOP prolongs PFS, as compared with placebo plus R-CHOP alone in subjects ≤75 years with previously untreated non-GCB DLBCL (ABC or unclassified) selected by GEP, based on investigator-assessed response.

Secondary objectives 3

1. To evaluate EFS with acalabrutinib plus R-CHOP compared with placebo plus R-CHOP in subject ≤75 years with previously untreated non-GCB DLBCL (ABC or unclassified) selected by GEP, as assessed by investigator
2. To evaluate CR rate with acalabrutinib plus R-CHOP compared with placebo plus R-CHOP in subjects ≤75 years with previously untreated non-GCB DLBCL (ABC or unclassified) selected by GEP, as assessed by BICR (Blinded Independent Central Review)
3. To evaluate overall survival (OS) with acalabrutinib plus R-CHOP compared with placebo plus R-CHOP in subjects ≤75 years with previously untreated non-GCB DLBCL (ABC or unclassified) selected by GEP

Conditions and MedDRA coding

Diffuse large B-cell lymphoma

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

IPD plan description

To facilitate the response to RFI CT-2023-509358-72-00-IN-002, the field has been designated as "undecided". This field will be updated in subsequent applications with Part I in scope.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Men and women, age ≥18 and ≤75 years
2. Pathologically confirmed DLBCL, sufficient diagnostic material should be available to forward to a central laboratory for gene expression profiling and pathology review.
3. No prior treatment for DLBCL
4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
5. International Prognostic Index (IPI) score of 1 to 5
6. Disease Stage II to IV by the Ann Arbor Classification
7. Adequate organ and marrow function
8. Agreement to use highly effective forms of contraception during the study and 12 months after the last dose of rituximab

Exclusion criteria 12

1. Evidence of severe or uncontrolled systemic diseases
2. Known history of a bleeding diathesis (i.e., haemophilia, von Willebrand disease)
3. History of stroke or intracranial hemorrhage in preceding 6 months.
4. Known CNS lymphoma or leptomeningeal disease
5. Known primary mediastinal lymphoma
6. Known High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements
7. Prior history of indolent lymphoma or CLL
8. History of or ongoing confirmed PML
9. Significant cardiovascular disease such as uncontrolled or 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
10. 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.
11. Uncontrolled active systemic fungal, bacterial, viral, or other infection
12. Prior anthracycline use ≥150 mg/m2

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-free survival (PFS) per the Lugano Classification for NHL in Arm A compared to Arm B

Secondary endpoints 3

1. Investigator-assessed event-free survival (EFS) for NHL in Arm A compared to Arm B
2. Percentage of Participants Who Achieved a Complete Response (CR) per 2014 Lugano Classification for NHL
3. Overall survival in Arm A compared to Arm B

Investigational products

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

Test 6

Placebo 1

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

Clinical Study Information Center

Public contact point

Organisation

Acerta Pharma B.V.

Contact name

Clinical Study Information Center

Third parties 10

Locations

9 EU/EEA countries · 81 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 66 files

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

Application history

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