A Study Evaluating the Safety and Efficacy of Polatuzumab Vedotin in Combination with Rituximab Plus Gemcitabine Plus Oxaliplatin (R- GEMOX) Versus R- GEMOX Alone in Patients with Relapsed/Refractory 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

28 Nov 2019 → 30 Nov 2024

Decision date (initial)

2024-09-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche AG

External identifiers

EU CT number

2024-512537-33-00

EudraCT number

2018-003727-10

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Others, Safety

To evaluate the efficacy of Pola-R-GemOx compared with R-GemOx alone on basis of the overall survival (OS) (Stage 2) To evaluate the safety and tolerability of Polatuzumab Vedotin (Pola)-R-GemOx as a combination therapy on basis of incidence, nature and severity of physical findings and adverse events (AEs), with a specific focus on peripheral neuropathy (PN), according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5 (NCI CTCAE v5.0) (Stage 1)

Secondary objectives 4

1. To evaluate safety and tolerability of Pola-R-GemOx as a combination therapy compared to R-GemOx, on the basis of incidence and assessment of peripheral neuropathy, tolerability, prevalence of anti-drug antibodies (ADA), incidence/nature/severity of AEs (Stage 1, 2)
2. To evaluate efficacy of Pola-R-GemOx compared to R-GemOx alone, on the basis of complete response (CR), objective response rate (ORR), best overall response (BOR), progression-free survival (PFS), event-free survival (EFS) (Stage 1, 2), OS (Pola-R-GemOx)- (Stage 1), duration of OR (DOR) (Stage 2)
3. To evaluate immunogenicity of polatuzumab vedotin, on the basis of prevalence of ADAs (Stage 1, 2)
4. To evaluate the impact of treatment, disease on aspects of health-related quality of life (Stage 2)

Conditions and MedDRA coding

Relapsed/refractory diffuse large B-cell lymphoma (DLBCL)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Histologically-confirmed DLBCL, not otherwise specified or history of transformation of indolent disease to DLBCL
2. Relapsed or refractory disease
3. At least one (>= 1) line of prior systemic therapy
4. At least one bi-dimensionally measurable lesion
5. Eastern Cooperative Oncology Group performance status of 0, 1 or 2
6. Adequate hematological function

Exclusion criteria 6

1. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies (or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products
2. Contraindication to rituximab, gemcitabine or oxaliplatin
3. Peripheral neuropathy assessed to be > Grade 1 according to NCI CTCAE v5.0 at enrollment
4. Prior use of polatuzumab vedotin or a gemcitabine + platinum-based agent combination
5. Enrollment in any previous or ongoing polatuzumab vedotin trial
6. Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational agent for the purposes of treating cancer within 2 weeks prior to Cycle 1 Day 1

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 1. Incidence, nature and severity of physical findings and AEs, with a specific focus on peripheral neuropathy, according to the NCI CTCAE v5.0 (Stage 1)
2. 2. Overall survival (Stage 2)

Secondary endpoints 16

1. 1. Incidence and assessment of peripheral neuropathy, as measured by Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 12-Item Scale (FACT-/GOG-NTX-12) (Stage 1)
2. 2. Incidence, nature and severity of AEs (including peripheral neuropathy) according to NCI CTCAE v5.0 and physical findings (Stage 2)
3. 3. Tolerability, as measured by dose interruptions, dose reductions and dose intensity (Stage 1 and 2)
4. 4. Prevalence of ADAs to polatuzumab vedotin at baseline and incidence of ADAs during the study (Stage 1 and 2)
5. 5. CR as determined by an independent review committee (IRC) (Stage 2)
6. 6. CR as determined by investigator (Stage 1 and 2)
7. 7. ORR as determined by an IRC (Stage 2)
8. 8. ORR as determined by investigator (Stage 1 and 2)
9. 9. BOR as determined by investigator (Stage 1 and 2)
10. 10. PFS as determined by investigator (Stage 1 and 2)
11. 11. OS (Stage 1)
12. 12. Event-free survival (EFSeff ) as determined by investigator (Stage 1 and 2)
13. 13. DOR as determined by investigator (Stage 2)
14. 14. Time to deterioration in physical functioning and fatigue as measured by the European Organisation for the Research and Treatment of Cancer Quality-of-Life Questionnaire, Core 30 (Stage 2)
15. 15. Time to progression in lymphoma symptoms as measured by the Functional Assessment of Cancer Therapy-Lymphoma subscale (Stage 2)
16. 16. Change from baseline in peripheral neuropathy as measured by the FACT/GOG-NTX-12 subscale score (Stage 2)

Investigational products

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

Test 4

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 16

Locations

5 EU/EEA countries · 19 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 7 files

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

Application history

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