Phase II multicenter clinical trial: Mosunetuzumab for early relapse of follicular lymphoma in the Nordic countries (MERLIN/NLG-FL6/ML43841)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Oslo University Hospital Hf

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15], Diseases [C] - Neoplasms [C04]

Trial duration

11 Sep 2023 → ongoing

Decision date (initial)

2023-02-07

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Oslo University Hospital · F.Hoffman-La Roche Ltd.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

The primary objective is to investigate the efficacy of 2nd line treatment with subcutaneous mosunetuzumab monotherapy in FL with refractory disease, progression or relapse of disease within 24 months of starting 1st line treatment (POD24).

Secondary objectives 6

1. Investigate response rates as determined by the investigator and survival.
2. Investigate the safety of SC mosunetuzumab monotherapy in patients with a current/recent POD24 event.
3. Investigate the prognostic significance of FDG-PET-CT response to mosunetuzumab in 2nd line treatment of POD24 patients.
4. Investigate the rate of transformation to higher grade lymphoma following single-agent mosunetuzumab in 2nd line treatment of POD24 patients.
5. Investigate patients´ self-reported quality of life (QoL) during and after single-agent mosunetuzumab therapy.
6. Investigate resource usage related to SC mosunetuzumab monotherapy.

Conditions and MedDRA coding

Follicular lymphoma

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Written informed consent according to ICH-GCP guidelines
2. Age ≥ 18 years
3. Follicular lymphoma grade 1-3a with a current relapse or progression within 24 months of starting 1st line treatment or refractory to 1st line treatment (POD24), more specifically: a. Documented current relapse or progression of FL within 24 months of starting first line treatment containing a monospecific anti-CD20 antibody (such as rituximab or obinutuzumab with or without chemotherapy, small molecular inhibitors or immunomodulating agents such as lenalidomide). b. Alternatively, current lack of response/refractoriness to first line treatment, i.e., no objective response or documented progression within 6 months following at least four cycles of monotherapy with a monospecific anti-CD20 antibody (such as rituximab 375mg/m2 iv or 1400 mg SC or equal) or following at least three cycles of a monospecific anti CD20 antibody combined with chemotherapy, small molecular inhibitors or immunomodulating agents such as lenalidomide. c. Received one prior treatment line of systemic therapy. d. If the POD24 event was diagnosed more than three months ago, then study inclusion has been clarified with the coordinating investigator. e. Patients may have received localized radiotherapy previously. Patients may have received localized radiotherapy previously. If the radiotherapy was recent, the patient must have at least one progressive and measurable lesion outside the radiation field.
4. At least one two-dimensionally measurable lesion with a longest diameter >15mm.
5. WHO performance status 0-2. Patients with reduced WHO performance status (> 2) can be considered if reduction in performance is caused by the lymphoma as determined by the investigator.

Exclusion criteria 24

1. Received 2 or more previous treatment lines.
2. Other current severe medical problems or expected survival of less than approximately five years for non-lymphoma reasons.
3. Current or previous other malignancy within three years of study entry, except cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other non-invasive or indolent malignancy without sponsor approval.
4. CD20-negative lymphoma
5. Psychiatric disorder or dementia which make the patient unable to give an informed consent and/or adhere to the schedule.
6. Pregnancy or breast-feeding.
7. CNS involvement (current or previous)
8. Impaired bone marrow function (neutrophils < 1.0 x 10^9/L or platelets < 50 x 10^9/L) unless due to lymphoma involvement
9. Severe cardiac disease: impaired cardiac function (NYHA class III or IV), myocardial infarction within the last 6 months, unstable arrythmias and/or unstable angina pectoris.
10. Impaired liver function not caused by lymphoma, defined as serum total bilirubin ≥ 1.5 x ULN (unless elevated due to Gilbert’s syndrome) or serum ALT and AST ˃ 3 x ULN
11. Impaired renal function not caused by lymphoma, defined as calculated creatinine clearance <= 40 ml/minute
12. Grade 3b FL.
13. Other major organ dysfunction not caused by lymphoma
14. Known history of drug induced liver injury, chronic active hepatitis C (HCV), chronic active hepatitis B (HBV), alcoholic liver disease, primary biliary cirrhosis, on-going extra-hepatic obstruction caused by cholelithiasis, cirrhosis of the liver or portal hypertension.
15. HIV positivity: Subjects that are on HIV-treatment with undetectable HIV-RNA and CD4-counts above 200 will be eligible.
16. Women of reproductive potential not agreeing to use an acceptable method of birth control during treatment and for three months after completion of treatment.
17. Hepatitis B (HBV) or hepatitis C (HCV) infection: Subjects with a previous hepatitis B infection will be eligible if they are negative for HBV-DNA; these subjects must be given prophylactic antiviral therapy. Subjects with a previous HCV infection will be eligible if they are negative for HCV-RNA.
18. Known or suspected chronic active Epstein-Barr virus (EBV) infection.
19. Received systemic immunosuppressive medications (including but not limited to cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within two weeks prior to the first dose of mosunetuzumab.
20. Administration of live vaccines within four weeks of the first dose of mosunetuzumab or anticipation that live vaccine will be required during the study.
21. History of severe allergic or anaphylactic reactions to chimeric, human, or humanized antibodies, or fusion proteins.
22. Known or suspected hemophagocytic syndrome.
23. Prior allogeneic hematopoietic stem cell transplant.
24. Active severe infection.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression free survival (within an observation time of a minimum of two years and a maximum of four years depending on the timepoint of patient inclusion in the trial

Secondary endpoints 14

1. Complete response rate (CRR) by FDG-PET-CT to 8 cycles of mosunetuzumab
2. Overall response rate (ORR) by FDG-PET-CT to 8 cycles of mosunetuzumab
3. Best CRR and ORR (by CT) to all administered cycles of mosunetuzumab
4. CRR and ORR (by CT) at 30 months after start of treatment
5. Duration of response (DOR) from the first occurrence of documented response by FDG-PET-CT to disease progression or death of any cause.
6. Time to new lymphoma treatment (from inclusion to the start of treatment other than mosunetuzumab due to progression of disease or to death of any cause).
7. PFS stratified by type of first line treatment (R monotherapy versus R combined with chemotherapy or other agents).
8. PFS by FDG-PET-CT response groups according to the 2014 Lugano Classification (from inclusion to the first occurrence of disease progression as determined by investigator or death from any cause).
9. Overall survival (OS) from inclusion to death of any cause.
10. Safety and tolerability of treatment, as the percentage of patients with adverse events (AEs) and the rate of dropout due to AEs.
11. Histology at relapse or progression occurring after or during study treatment.
12. Rate of transformation to higher-grade lymphoma.
13. Resource usage during treatment such as the rate of hospitalizations and duration of hospitalizations due to mosunetuzumab treatment and/or AEs and the number of out-patient consultations due to mosunetuzumab treatment and/or AEs.
14. Quality of life during and after treatment (as measured by EORTC QLQ-C30 and by EQ-5D).

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Oslo University Hospital Hf

Sponsor organisation

Oslo University Hospital Hf

Address

Taarnbygget, Kirkeveien 166 Kirkeveien 166

City

Oslo

Postcode

0450

Country

Norway

Scientific contact point

Organisation

Oslo University Hospital Hf

Contact name

Coordinating Investigator

Public contact point

Organisation

Oslo University Hospital Hf

Contact name

Coordinating Investigator

Third parties 1

Locations

4 EU/EEA countries · 21 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 16 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