A Study to Evaluate the Efficacy and Safety of Polatuzumab Vedotin in Combination with Rituximab and CHP (R-CHP) Versus Rituximab and CHOP (R-CHOP) in Previously Untreated Patients with Diffuse Large B-Cell Lymphoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

27 Mar 2018 → 7 May 2026

Decision date (initial)

2024-11-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann La Roche

External identifiers

EU CT number

2024-516904-40-00

EudraCT number

2017-002023-21

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety, Efficacy, Pharmacokinetic

To evaluate the efficacy of polatuzumab vedotin plus rituximab plus cyclophosphamide, doxorubicin, and prednisone (R-CHP) compared with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with respect to progression-free survival (PFS)

Secondary objectives 4

1. To evaluate the efficacy of polatuzumab vedotin plus R-CHP compared with R-CHOP with respect to secondary efficacy endpoints
2. To evaluate the safety of polatuzumab vedotin plus R-CHP compared with R-CHOP
3. To characterize the pharmacokinetics of polatuzumab vedotin
4. To evaluate the immune response to polatuzumab vedotin

Conditions and MedDRA coding

Previously Untreated Diffuse large B-cell lymphoma (DLBCL)

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

IPD plan description

N/A

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Previously untreated patients with CD20-positive DLBCL, including one of the following diagnoses by 2016 WHO classification of lymphoid neoplasms: – DLBCL, not otherwise specified (NOS) including germinal center B-cell type, activated B-cell type – T-cell/histiocyte-rich large B-cell lymphoma – Epstein-Barr virus-positive DLBCL, NOS – ALK-positive large B-cell lymphoma – HHV8-positive DLBCL, NOS – High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (double-hit or triple-hit lymphoma) – High-grade B-cell lymphoma, NOS
2. International Prognostic Index (IPI) score of 2-5
3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
4. Life expectancy ≥ 12 months
5. At least one bi-dimensionally measurable lesion, defined as >1.5 cm in its longest dimension as measured by computed tomography (CT) or magnetic resonance imaging (MRI)
6. Left ventricular ejection fraction (LVEF) ≥ 50% on cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram (ECHO)

Exclusion criteria 6

1. Prior organ transplantation
2. Current Grade >1 peripheral neuropathy by clinical examination or demyelinating form of Charcot-Marie-Tooth disease
3. History of indolent lymphoma
4. Prior treatment with cytotoxic drugs within 5 years of screening for any condition (e.g., cancer, rheumatoid arthritis) or prior use of any anti-CD20 antibody
5. Prior use of any monoclonal antibody within 3 months of the start of Cycle 1; any investigational therapy within 28 days prior to the start of Cycle 1; vaccination with live vaccines within 28 days prior the start of Cycle 1
6. Prior radiotherapy to the mediastinal/pericardial region

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. Progression-free survival, defined as the time from randomization to the first occurrence of disease progression or relapse as assessed by the investigator by using the Lugano Response Criteria for Malignant Lymphoma, or death from any cause, whichever occurs earlier

Secondary endpoints 17

1. 1. Event-free survival (efficacy) as determined by the investigator
2. 2. Complete response rate at end of treatment by fluorodeoxyglucose positron emission tomography (FDG-PET) as determined by blinded independent central review (BICR)
3. 3. Overall Survival (OS)
4. 4. CR rate at end of treatmentby FDG-PET as determined by the investigator
5. 5. 2-year progression-free survival rate (PFS24) as determined by the investigator
6. 6. Disease-free survival (DFS)
7. 7. Duration of response (DOR)
8. 8. Event-free survival (all causes)
9. 9. Time to deterioration in european organisation for research and treatment of cancer quality of life-core 30 questionnaire (EORTC QLQ-C30) physical functioning and fatigue and functional assessment of cancer therapy-lymphoma lymphoma subscale (FACT-Lym LymS)
10. 10. Proportion of patients achieving meaningful improvement in EORTC QLQ-C30 physical functioning and fatigue, and FACT-Lym LymS
11. 11. EORTC QLQ-C30 rate of treatment-related symptoms and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group – Neurotoxicity (FACT/GOG-NTX) peripheral neuropathy rate
12. 12. Incidence, nature, and severity of adverse events, with severity determined through use of national cancer institute common terminology criteria for adverse events, version 4.0 (NCI CTCAE v4.0)
13. 13. Incidence of peripheral neuropathy rates and severity determined through use of NCI CTCAE v4.0
14. 14. Incidence and nature of study drug discontinuation, dose reduction, and dose delay due to adverse events
15. 15. Dose intensities of study drugs
16. 16. Plasma and/or serum concentration of polatuzumab vedotin related analytes at specified time points
17. 17. Incidence of anti-drug antibodies (ADAs) to polatuzumab vedotin during the study relative to the prevalence of ADAs to polatuzumab vedotin at baseline

Investigational products

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

Test 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation

F. Hoffmann-La Roche AG

Address

Grenzacherstrasse 124

City

Basel

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Third parties 6

Locations

8 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 105 files

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

Application history

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