This is an open-label multicenter randomized non comparative phase II study to evaluate the safety and efficacy of the monoclonal anti-KIR3DL2 antibody Lacutamab in patients with Refractory/Relapsing (R/R) KIR3DL2 positive Peripheral T Cell Lymphoma (PTCL) : Not Other Specified (NOS), PTCL-TFH (including Angioimmunoblastic T-cell Lymphoma (AITL), Follicular T-cell lymphoma, Nodal peripheral T-cell lymphoma with TFH phenotype), Anaplastic large cell lymphoma (ALCL), Adult T-cell leukemia/lymphoma (ATL), Hepatosplenic T-cell lymphoma (HSTL), Enteropathy-associated T-cell lymphoma (EATL), Monomorphic epitheliotropic intestinal T cell lymphoma (MEITL), NK-T cell lymphoma (NKT) and Aggressive NK-cell leukemia (ANKL).
The design is non comparative meaning that non comparison between arms will be performed as the control arm will ensure that the assumptions used for sample size calculation are verified. For that reason, randomization is unbalanced in favor of the experimental arm (2:1).
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
* 1\. KIR3DL2-positive with at least 1% of tumour cells positivity, before randomization, based on central evaluation by immunohistochemistry (IHC) 2. Patients with histologically documented PTCL:
* Biopsy-proven treated PTCL defined by the WHO 2016 criteria (the biopsy at relapse is recommended but not mandatory):
* PTCL-NOS
* PTCL-TFH (AITL, Follicular T-cell lymphoma, Nodal peripheral T-cell lymphoma with TFH phenotype)
* ALCL
* ATL: acute- or lymphoma-type
* HSTL
* EATL
* MEITL
* NKT
* ANKL 3. For patients with ALCL: previously treated with brentuximab vedotin 4. Relapsed/refractory PTCL after at least one previous line of systemic based regimen of chemotherapy (no mandatory latency after the previous treatment) 5. With a maximum of 2 prior lines of systemic therapies, including autologous stem cell transplantation (ASCT is authorized in first and second line and is not counted as a unique line, even if associated to a systemic therapy) 6. Bi-dimensionally measurable disease defined by at least one single node or tumor lesion ≥ 1.5 cm assessed by CT scan 7. Signed written screening informed consent prior to KIR3DL2 screening 8. Signed written study informed consent prior to randomization 9. Aged 18 years or more with no upper age limit, at randomization 10. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 3 prior to prephase treatment (if applicable), and 0 to 2 prior randomization 11. Minimum life expectancy of 3 months 12. Females of childbearing potential (FCBP) must agree to use highly effective contraceptive method\* from C1D1, during the entire study period, during dose interruptions, and for 9 months after the last study treatments 13. FCBP must have a negative serum or urinary pregnancy test within 28 days prior C1D1 14. Male patients and their partner (FCBP) must agree to use two reliable forms of contraception (condom for males and hormonal method for partners) from C1D1, during the entire study period, during dose interruptions, and for 9 months after the last study treatments
Exclusion Criteria:
* 1\. Patients with active COVID-19 infection (last positive PCR \< 2 weeks before randomization) 2. Patients taking immunotherapy or chemotherapy, except short-term corticosteroids in monotherapy at a cumulated dose equivalent of prednisone ≤ 1mg/kg/day, during 7 consecutive days, within 3 weeks prior to first administration of study drug (C1D1); or prephase treatment given at investigator's discretion before randomization and for maximum 3 weeks (glucocorticosteroids, vepesid (VP16), cyclophosphamide, vincristine and prednisone (COP)) 3. Previous treatment by Gemcitabine or Oxaliplatin 4. Use of any experimental anti-cancer drug therapy within 6 weeks before randomization 5. Contraindication to any drug contained in the study treatment regimen 6. Previous allogenic hematopoietic cell transplantation 7. Positive test results for HIV and Hepatitis C Virus (HCV) (Patients who are positive for HCV antibody must be negative for HCV by PCR to be eligible for study participation) 8. Known active hepatitis B (positive Ag HBs) (if latent Hepatitis B Virus (HBV) (positive anti-HBc), patients have to be treated with Entecavir (Baraclude ®) and HBV PCR should be performed every month to allow antiviral strategy adaptation) 9. Central nervous system or meningeal involvement by lymphoma 10. Any of the following laboratory abnormalities prior randomization:
* Absolute neutrophil count (ANC) \< 1 G/L, unless neutropenia is related to PTCL
* Platelet count \< 75 G/L, unless thrombopenia is related to PTCL
* Alkaline Phosphatases \> 2.5 x upper limit of normal (ULN)
* Serum Glutamoyl-oxaloacetate Transferase (SGOT) /Alanine aminotransferase (AST) or Serum Glutamate Pyruvate Transaminase (SGPT)/Alanine aminotransferase (ALT) \> 2.5 x ULN
* Bilirubin \> 1.5 x ULN, unless SGOT/AST and SGPT/ALT \> 2.5 x ULN or bilirubin elevated due to PTCL or hemolysis
* Calculated creatinine clearance (MDRD or Cockcroft) \< 40 mL/min 11. Any significant cardiovascular impairment: New York Heart Association (NYHA) Class III or IV cardiac disease, uncontrolled high blood pressure, unstable angina, myocardial infarction or stroke within the last 6 months from randomization, and cardiac arrhythmia within the last 3 months from randomization 12. Uncontrolled clinically significant intercurrent illness including, but not limited to, diabetes, ongoing active infections. Patients receiving antibiotics for infections that are under control may be included in the study 13. Concurrent malignancy or prior history of malignancies other than lymphoma unless the subject has been free of disease for ≥ 2 years, except early stage cutaneous squamous or basal cell carcinoma, localized prostate cancer, or cervical intraepithelial neoplasia 14. Major surgery within 4 weeks before randomization 15. Pregnant or lactating females
Primary outcome measure(s)
median modified progression-free survival (mPFS) - CT-based — 5,5 years. time from randomization until one of the following events occurs, whichever comes first:
1. Disease progression (PD)
2. Administration of any additional unplanned anti-lymphoma treatment (except allogeneic or autologous hematopoietic cell transplantations (HCT))
3. Relapse after achievement of CR
4. Death due to any cause. PD and relapse will be evaluated according to Lugano 2014 criteria (CT-based).
Trial sites (64)
Facility
City
Region
Status
Institut Jules Bordet
Anderlecht
Belgium
VZW ZAS
Antwerp
Belgium
A. Z. Sint-Jan
Bruges
Belgium
Cliniques Universitaires de Bruxelles - Hôpital Erasme
Brussels
Belgium
Cliniques universitaires Saint-Luc - Université catholique de Louvain
Brussels
Belgium
Grand Hôpital de Charleroi
Charleroi
Belgium
UZ Antwerpen
Edegem
Belgium
HELORA - Hôpital de La LouvièreSite Jolimont
Haine-Saint-Paul
Belgium
CHU de LIEGE - Domaine Sart Tilman
Liège
Belgium
Clinique CHC MontLégia
Liège
Belgium
CHR Verviers
Verviers
Belgium
CHU Dinant Godinne - UCL Namur - YVOIR
Yvoir
Belgium
CHU d'Amiens
Amiens
France
CHU d'Angers
Angers
France
CH d Avignon - Hopital Henri Duffaut
Avignon
France
CH de la Côte Basque - Hôpital de Bayonne
Bayonne
France
Institut Bergonié
Bordeaux
France
CHU de Caen - Côte de Nacre - IHBN
Caen
France
CH Métropole Savoie
Chambéry
France
CHU de Clermont Ferrand - Estaing
Clermont-Ferrand
France
APHP - Hôpital Henri Mondor
Créteil
France
CHU de Dijon BOURGOGNE - Hôpital François Mitterand
Dijon
France
CH de Dunkerque
Dunkirk
France
CHD de Vendée
La Roche-sur-Yon
France
CHU de Grenoble - Hôpital Albert Michallon
La Tronche
France
Ch de Versailles - Hopital Andre Mignot
Le Chesnay
France
CH du Mans
Le Mans
France
CHRU de Lille - Hôpital Claude Hurriez
Lille
France
Hôpital Saint Vincent-De-Paul
Lille
France
Chu de Limoges - Hopital Dupuytren
Limoges
France
Centre Leon Berard
Lyon
France
Chu de Meaux
Meaux
France
CHU de Montpellier
Montpellier
France
CH de Mulhouse
Mulhouse
France
CHU de Nancy - Brabois
Nancy
France
CHU de Nantes - Hôtel Dieu
Nantes
France
CHU de Nîmes
Nîmes
France
CHR d'Orléans
Orléans
France
APHP - Hopital Necker
Paris
France
APHP - Hôpital de la Pitié Salpétrière
Paris
France
+ 24 more sites — see the full list on the official registry below.
More The Lymphoma Academic Research Organisation trials in Belgium
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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