Primary treatment of follicular lymphoma with rituximab-lenalidomide-tafasitamab for high-risk disease and rituximab-lenalidomide with a 1:1 randomization to tafasitamab for low-risk disease: a phase II study – NLG-FL7

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Karolinska University Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

27 May 2025 → ongoing

Decision date (initial)

2025-02-27

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

To assess the efficacy of the addition of tafasitamab to rituximab-lenalidomide in primary treatment of follicular lymphoma.

Secondary objectives 3

1. Further assessments of the efficacy of the addition of tafasitamab to rituximab-lenalidomide
2. To compare the safety of tafasitamab and rituximab-lenalidomide versus rituximab-lenalidomide.
3. To evaluate QoL of tafasitamab and rituximab-lenalidomide versus rituximab-lenalidomide.

Conditions and MedDRA coding

Follicular lymphoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Written informed consent according to ICH-GCP guidelines
2. Age ≥ 18 and ≤ 85 years
3. Histologically confirmed follicular lymphoma (not grade 3B) stage II-IV not suitable for radiotherapy (preferably a surgical biopsy, core but not fine needle acceptable)
4. At least one two-dimensionally measurable lesion with a longest diameter > 15 mm
5. WHO performance status 0-2
6. At least one treatment indication of the following: 1. Symptomatic disease 2. Vital organ or vascular compression 3. Ascites or pleural effusion 4. Bulky disease (≥ 6 cm) 5. Steady, clinically significant progression over at least 3 months of any tumour lesion 6. B-symptoms (weight loss > 10% in 6 months, drenching night sweats or fever > 38°C not due to infection) 7. Anemia (hemoglobin < 100 g/L) or thrombocytopenia (platelets < 100 x 109/L) due to lymphoma
7. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, only after A. leaving a negative result on a highly sensitive pregnancy test, B. are using a highly effective method of contraception during treatment, and C. throughout the study and 4 weeks after the last dose of lenalidomide, 3 months after the last dose of tafasitamab and 12 months after the last dose of rituximab, whichever is latest. (An additional pregnancy test is to be provided at end of exposure). Highly effective methods of contraception include one or more of the following (see also Appendix 6): a. male partner who is sterile (vasectomised) prior to the female study subject’s entry into the study and is the sole sexual partner for the female subject; b. hormonal (oral, intravaginal, transdermal, implantable or injectable) c. an intrauterine hormone-releasing system (IUS) d. an intrauterine device (IUD) with a documented failure rate of < 1%.
8. Sexually active male participants must agree to use barrier prevention (condom) to ensure that embryos/fetuses are not exposed to study drugs via sperm, during treatment and for a week after completion of treatment. Female partners to male participants must if not postmenopausal or permanently sterilized (e.g. hysterectomy or tubal ligation) use a highly effective method of contraception to avoid accidental pregnancy during treatment and for a week after the last dose of lenalidomide..

Exclusion criteria 22

1. CD20-negative or CD19-negative lymphoma
2. Transformation to aggressive lymphoma (including grade 3B follicular lymphoma) at any time prior to starting treatment within the trial
3. CNS involvement of lymphoma at inclusion or previously
4. Previous systemic anti-lymphoma therapy, including chemotherapy or antibodies; however, steroids to alleviate lymphoma symptoms and preclude tumor lysis prior to and during the first course of trial therapy are allowed
5. Anti-lymphoma radiotherapy <3 months prior to start of trial therapy (local radiotherapy before that timepoint is allowed)
6. Impaired bone marrow function (neutrophils < 1.0 x 109/L or platelets < 50 x 109/L) unless due to lymphoma involvement
7. Severe cardiac disease: cardiac function (NYHA III or IV)
8. Impaired liver function not caused by lymphoma, defined as serum total bilirubin > 2 x ULN (> 3 x ULN if Gilbert’s syndrome) or serum ALT and AST ˃ 3 x ULN
9. Estimated glomerular filtration rate (eGFR) <30 mL/min, using the Cockcroft-Gault equation, if not caused by lymphoma
10. Estimated glomerular filtration rate (eGFR) <10 mL/min, using the Cockcroft-Gault equation, even if caused by lymphoma
11. Other major organ dysfunction not caused by lymphoma
12. Known history of drug induced liver injury, alcoholic liver disease, primary biliary cirrhosis, on-going extra-hepatic obstruction caused by cholelithiasis, cirrhosis of the liver or portal hypertension
13. Hepatitis B (HBV): a history of past or present hepatitis B infection (according to serology or DNA) is not allowed.
14. Subjects with a previous HCV infection will be eligible if they are negative for HCV-RNA.
15. Patients with other severe medical problems causing an expected survival <1 year for non-lymphoma reasons
16. Current or previous other malignancy within 2 years of study entry, except cured basal or squamous cell skin cancer, superficial bladder cancer, low grade prostate cancer without therapy, and carcinoma in situ of the cervix, or other noninvasive or indolent malignancy
17. Psychiatric disorder or dementia which make the patient unable to give an informed consent and/or adhere to the schedule
18. Pregnancy or breast-feeding
19. HIV positivity
20. Men and women of reproductive potential not agreeing to use an acceptable method of birth control during treatment and for six months after completion of treatment
21. Unwilling or unable to take prophylaxis against a thromboembolic event
22. Patients with an active infection which needs clinical intervention

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. EFS24, defined as the interval between treatment start and progression or new lymphoma treatment or death, whichever occurs first, within 2 years of study entry.

Secondary endpoints 12

1. EFS, defined as the interval between treatment start and progression or new lymphoma treatment or death, whichever occurs first.
2. PFS, defined as the interval between treatment start and progression or death, whichever occurs first.
3. POD24, defined as the interval between treatment start and progression or death, whichever occurs first, within 2 years of study entry.
4. OS, defined as the interval between treatment start and death.
5. ORR, defined as the sum of the rates of CR or PR at best response.
6. CRR, defined as the sum of the rates of CR at best response.
7. LSS, defined as the interval between treatment start and death of lymphoma (other causes are censored at the date of death).
8. Time to next treatment, defined as the interval between treatment start and that of documented new anti-lymphoma therapy.
9. Duration of response, defined as the interval between when criteria for response (CR or PR) are met to the first documentation of progression.
10. Incidence of transformation. Cases of transformation are documented with respect to transformation type and date.
11. Safety based on the incidence and severity of AEs. Frequency and duration of all grade 3-5 treatment-related adverse events (AEs) according to CTCAE 5.0.
12. HR-QoL as measured by EORTC QLQ-C30

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Karolinska University Hospital

Sponsor organisation

Karolinska University Hospital

Address

Eugeniavagen 3

City

Solna

Postcode

171 64

Country

Sweden

Scientific contact point

Organisation

Karolinska University Hospital

Contact name

Björn Wahlin

Public contact point

Organisation

Karolinska University Hospital

Contact name

Björn Wahlin

Third parties 2

Locations

5 EU/EEA countries · 22 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 39 files

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

Application history

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