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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04984837
Other study ID # KILT
Secondary ID
Status Recruiting
Phase Phase 2
First received
Last updated
Start date October 5, 2021
Est. completion date January 30, 2027

Study information

Verified date December 2023
Source The Lymphoma Academic Research Organisation
Contact Baptiste LAVERROUX
Phone +33 4 27 01 27 18
Email kilt@lysarc.org
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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).


Recruitment information / eligibility

Status Recruiting
Enrollment 56
Est. completion date January 30, 2027
Est. primary completion date January 30, 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Study Design


Intervention

Drug:
Lacutamab
750 mg/IV
Gemcitabine
1000 mg/m²
Oxaliplatine
100 mg/m²

Locations

Country Name City State
Belgium Institut Jules Bordet Anderlecht
Belgium ZNA Cadix Antwerpen
Belgium A. Z. Sint-Jan Bruges
Belgium Cliniques universitaires Saint-Luc - Université catholique de Louvain Brussels
Belgium Cliniques Universitaires de Bruxelles - Hôpital Erasme Bruxelles
Belgium Grand Hôpital de Charleroi Charleroi
Belgium Universitair Ziekenhuis 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
France 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 Dunkerque
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 Orleans
France APHP - Hôpital de la Pitié Salpétrière Paris
France APHP - Hopital Necker Paris
France APHP - Hôpital Saint Antoine Paris
France APHP - Hôpital Saint Louis Paris
France CH de Périgueux Périgueux
France CH de Perpignan Perpignan
France CHU de Bordeaux - Hôpital Haut Lévêque - Centre François Magendie Pessac
France Centre Hospitalier Lyon Sud Pierre Bénite
France CHU de Poitiers - Hôpital de La Milétrie Poitiers
France Centre Hospitalier Annecy Genevois Pringy
France CHU de Reims Reims
France CHU de Rennes - Hôpital de Pontchaillou Rennes
France Centre Henri Becquerel Rouen
France Institut de Cancérologie et d'Hématologie Universitaire de Saint-Étienne Saint-Étienne
France Institut de Cancerologie Strasbourg Europe Strasbourg
France Institut Universitaire du Cancer de Toulouse - Oncopole Toulouse
France CH de Bretagne Atlantique - Hopital Chubert Vannes
Germany Charite Universitat Smedizin Berlin Berlin
Germany GEORG-AUGUST-UNIV, GOETTINGEN - Klinik fur Haematologie und Medizini Goettigen
Germany Universitatsklinikum Halle (Saale) Halle
Germany UNIVERSITAT LEIPZIG - Klinik fur Hamatologie, Zelltherapie und Hamostaseo Leipzig
Germany UNIVERSITATSKLINIKUM REGENSBURG - Klinik für Innere Medizin III Regensburg
Spain Hospital Universitari Vall d'Hebron Barcelona
Spain Hospital Universitario Fundacion Jimenez Diaz - Hematologia Madrid
Spain Hospital Universitario Marqués de Valdecilla Santander
Spain Hospital Clínico Universitario de Valencia Valencia

Sponsors (2)

Lead Sponsor Collaborator
The Lymphoma Academic Research Organisation Innate Pharma

Countries where clinical trial is conducted

Belgium,  France,  Germany,  Spain, 

Outcome

Type Measure Description Time frame Safety issue
Primary median modified progression-free survival (mPFS) - CT-based time from randomization until one of the following events occurs, whichever comes first:
Disease progression (PD)
Administration of any additional unplanned anti-lymphoma treatment (except allogeneic or autologous hematopoietic cell transplantations (HCT))
Relapse after achievement of CR
Death due to any cause. PD and relapse will be evaluated according to Lugano 2014 criteria (CT-based).
5,5 years.
Secondary median modified progression-free survival (mPFS) - PET-based 5,5 years.
Secondary Number of Adverse Events 5,5 years.
Secondary overall survival (OS) 5,5 years.
Secondary complete response rate (CRR) Lugano 2014 criteria (CT-based) 5,5 years.
Secondary complete response rate (CRR) Lugano 2014 criteria (PET-based) 5,5 years.
Secondary overall response rate (ORR) Lugano 2014 criteria (CT-based) 5,5 years.
Secondary overall response rate (ORR) Lugano 2014 criteria (PET-based) 5,5 years.
Secondary response rate assessed by Deauville criteria 5,5 years.
Secondary duration of response (DOR), Disease progression (PD)
Administration of any additional unplanned anti-lymphoma treatment (except allogeneic or autologous hematopoietic cell transplantations (HCT))
Relapse after achievement of CR
Death due to any cause
5,5 years.
Secondary rate of patients proceeding to allogenic stem cell transplantation 5,5 years.
Secondary Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax) 1 month (1 cycle)
Secondary Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough) 1 month (1 cycle)
Secondary Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax) 2 months (2 cycles)
Secondary Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough) 2 months (2 cycles)
Secondary Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax) 3 months (3 cycles)
Secondary Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough) 3 months (3 cycles)
Secondary Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax) 7 months (7 cycles)
Secondary Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough) 7 months (7 cycles)
Secondary Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax) 9 months (9 cycles)
Secondary Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough) 9 months (9 cycles)
Secondary Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax) 15 months (15 cycles)
Secondary Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough) 15 months (15 cycles)
Secondary Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax) 26 months (26 cycles)
Secondary Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough) 26 months (26 cycles)
Secondary Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax) 29 months (29 cycles)
Secondary Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough) 29 months (29 cycles)
Secondary Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx 1 month (1 cycle)
Secondary Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx 2 months (2 cycles)
Secondary Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx 3 months (3 cycles)
Secondary Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx 7 months (7 cycles)
Secondary Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx 9 months (9 cycles)
Secondary Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx 15 months (15 cycles)
Secondary Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx 26 months
Secondary Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx 29 months
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