Study of Lacutamab in Peripheral T-cell Lymphoma

Phase 2

Recruiting

• Conditions: Peripheral T Cell Lymphoma; Relapse/Recurrence
• Interventions: Drug: Lacutamab; Drug: Gemcitabine; Drug: Oxaliplatine

• Registration Number: NCT04984837
• Lead Sponsor: The Lymphoma Academic Research Organisation

Brief 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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-07-18
• Study First Submitted QC: 2021-07-28
• Study First Posted: 2021-08-02
• Study Start: 2021-10-05
• Status Verified: 2025-02
• Last Update Submitted: 2025-03-03
• Last Update Posted: 2025-03-05
• Primary Completion: 2026-01-30
• Study Completion: 2028-01-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 56

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lacutamab	Lacutamab	Lacutamab 750 mg/IV + GEmOx (1000 mg/m² / 100 mg/m²) 6 cycles of 3 weeks (4,5 months) during the induction phase Lacutamab 750 mg/IV for a maximum of 20 additional cycles of 4 weeks during the maintenance phase
Lacutamab	Gemcitabine	Lacutamab 750 mg/IV + GEmOx (1000 mg/m² / 100 mg/m²) 6 cycles of 3 weeks (4,5 months) during the induction phase Lacutamab 750 mg/IV for a maximum of 20 additional cycles of 4 weeks during the maintenance phase
Standard of care	Gemcitabine	GemOx (1000 mg/m² / 100 mg/m²) 6 cycles of 3 weeks (4,5 months) during the induction phase
Lacutamab	Oxaliplatine	Lacutamab 750 mg/IV + GEmOx (1000 mg/m² / 100 mg/m²) 6 cycles of 3 weeks (4,5 months) during the induction phase Lacutamab 750 mg/IV for a maximum of 20 additional cycles of 4 weeks during the maintenance phase
Standard of care	Oxaliplatine	GemOx (1000 mg/m² / 100 mg/m²) 6 cycles of 3 weeks (4,5 months) during the induction phase

Primary Outcome Measures

Name	Time	Method
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).

Secondary Outcome Measures

Name	Time	Method
complete response rate (CRR) Lugano 2014 criteria (CT-based)	5,5 years.
Number of Adverse Events	5,5 years.
complete response rate (CRR) Lugano 2014 criteria (PET-based)	5,5 years.
overall survival (OS)	5,5 years.
rate of patients proceeding to allogenic stem cell transplantation	5,5 years.
Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax)	29 months (29 cycles)
overall response rate (ORR) Lugano 2014 criteria (CT-based)	5,5 years.
Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough)	29 months (29 cycles)
Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx	29 months
median modified progression-free survival (mPFS) - PET-based	5,5 years.
overall response rate (ORR) Lugano 2014 criteria (PET-based)	5,5 years.
response rate assessed by Deauville criteria	5,5 years.
duration of response (DOR),	5,5 years.	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

Trial Locations

Locations (64)

Chu de Meaux; 🇫🇷 Meaux, France

Clinique CHC MontLégia; 🇧🇪 Liège, Belgium

CHU Dinant Godinne - UCL Namur - YVOIR; 🇧🇪 Yvoir, Belgium

CHU d'Angers; 🇫🇷 Angers, France

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

CHR Verviers; 🇧🇪 Verviers, Belgium

HELORA - Hôpital de La LouvièreSite Jolimont; 🇧🇪 Haine-Saint-Paul, Belgium

CHU de LIEGE - Domaine Sart Tilman; 🇧🇪 Liège, Belgium

CHU d'Amiens; 🇫🇷 Amiens, France

CH de la Côte Basque - Hôpital de Bayonne; 🇫🇷 Bayonne, France

CH d Avignon - Hopital Henri Duffaut; 🇫🇷 Avignon, France

Institut Bergonié; 🇫🇷 Bordeaux, France

CH Métropole Savoie; 🇫🇷 Chambéry, France

CHU de Caen - Côte de Nacre - IHBN; 🇫🇷 Caen, 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

CHU de Grenoble - Hôpital Albert Michallon; 🇫🇷 La Tronche, France

CHRU de Lille - Hôpital Claude Hurriez; 🇫🇷 Lille, France

CHD de Vendée; 🇫🇷 La Roche-sur-Yon, France

Ch de Versailles - Hopital Andre Mignot; 🇫🇷 Le Chesnay, France

CH du Mans; 🇫🇷 Le Mans, France

Hôpital Saint Vincent-De-Paul; 🇫🇷 Lille, France

Chu de Limoges - Hopital Dupuytren; 🇫🇷 Limoges, France

Centre Leon Berard; 🇫🇷 Lyon, France

CH de Mulhouse; 🇫🇷 Mulhouse, France

CHU de Nancy - Brabois; 🇫🇷 Nancy, France

CHU de Montpellier; 🇫🇷 Montpellier, France

CHU de Nîmes; 🇫🇷 Nîmes, France

APHP - Hopital Necker; 🇫🇷 Paris, France

APHP - Hôpital de la Pitié Salpétrière; 🇫🇷 Paris, France

CHU de Nantes - Hôtel Dieu; 🇫🇷 Nantes, France

CHR d'Orléans; 🇫🇷 Orleans, France

APHP - Hôpital Saint Antoine; 🇫🇷 Paris, France

CHU de Bordeaux - Hôpital Haut Lévêque - Centre François Magendie; 🇫🇷 Pessac, France

APHP - Hôpital Saint Louis; 🇫🇷 Paris, France

CH de Perpignan; 🇫🇷 Perpignan, France

Centre Hospitalier Lyon Sud; 🇫🇷 Pierre Bénite, France

CH de Périgueux; 🇫🇷 Périgueux, France

CHU de Poitiers - Hôpital de La Milétrie; 🇫🇷 Poitiers, France

Centre Hospitalier Annecy Genevois; 🇫🇷 Pringy, France

CHU de Rennes - Hôpital de Pontchaillou; 🇫🇷 Rennes, France

CHU de Reims; 🇫🇷 Reims, 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, France

Charite Universitat Smedizin Berlin; 🇩🇪 Berlin, Germany

UNIVERSITAT LEIPZIG - Klinik fur Hamatologie, Zelltherapie und Hamostaseo; 🇩🇪 Leipzig, Germany

Universitatsklinikum Halle (Saale); 🇩🇪 Halle, Germany

GEORG-AUGUST-UNIV, GOETTINGEN - Klinik fur Haematologie und Medizini; 🇩🇪 Goettigen, Germany

UNIVERSITATSKLINIKUM REGENSBURG - Klinik für Innere Medizin III; 🇩🇪 Regensburg, Germany

Hospital Universitario Fundacion Jimenez Diaz - Hematologia; 🇪🇸 Madrid, Spain

Hospital Universitari Vall d'Hebron; 🇪🇸 Barcelona, Spain

Hospital Clínico Universitario de Valencia; 🇪🇸 Valencia, Spain

Hospital Universitario Marqués de Valdecilla; 🇪🇸 Santander, Spain