Study of Lacutamab in Peripheral T-cell Lymphoma

NCT04984837 | Recruiting Phase 2 DMC

• 1 other identifier: KILT
• Study Type: interventional
• Target: 56
• Locations: 4 countries
• Sites: 64

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).

Conditions

Peripheral T Cell Lymphoma; Relapse/Recurrence

Keywords

KIR3DL2; PTCL; T-cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• median modified progression-free survival (mPFS) - CT-based

  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).

  5,5 years.

Secondary Outcomes (34)

• median modified progression-free survival (mPFS) - PET-based

  5,5 years.

• Number of Adverse Events

  5,5 years.

• overall survival (OS)

  5,5 years.

• complete response rate (CRR) Lugano 2014 criteria (CT-based)

  5,5 years.

• complete response rate (CRR) Lugano 2014 criteria (PET-based)

  5,5 years.

Study Arms (2)

Lacutamab

EXPERIMENTAL

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

Drug: Lacutamab; Drug: Gemcitabine; Drug: Oxaliplatine

Standard of care

ACTIVE COMPARATOR

GemOx (1000 mg/m² / 100 mg/m²) 6 cycles of 3 weeks (4,5 months) during the induction phase

Drug: Gemcitabine; Drug: Oxaliplatine

Interventions

Lacutamab DRUG

750 mg/IV

Lacutamab

Gemcitabine DRUG

1000 mg/m²

Lacutamab; Standard of care

Oxaliplatine DRUG

100 mg/m²

Lacutamab; Standard of care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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

You may not qualify if:

• \. 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

Sponsors & Collaborators

• Innate Pharma: collaborator
• The Lymphoma Academic Research Organisation: lead

Study Sites (64)

Institut Jules Bordet

Anderlecht, Belgium

RECRUITING

VZW ZAS

Antwerp, Belgium

RECRUITING

A. Z. Sint-Jan

Bruges, Belgium

RECRUITING

Cliniques Universitaires de Bruxelles - Hôpital Erasme

Brussels, Belgium

SUSPENDED

Cliniques universitaires Saint-Luc - Université catholique de Louvain

Brussels, Belgium

RECRUITING

Grand Hôpital de Charleroi

Charleroi, Belgium

RECRUITING

UZ Antwerpen

Edegem, Belgium

RECRUITING

HELORA - Hôpital de La LouvièreSite Jolimont

Haine-Saint-Paul, Belgium

RECRUITING

CHU de LIEGE - Domaine Sart Tilman

Liège, Belgium

RECRUITING

Clinique CHC MontLégia

Liège, Belgium

RECRUITING

CHR Verviers

Verviers, Belgium

RECRUITING

CHU Dinant Godinne - UCL Namur - YVOIR

Yvoir, Belgium

RECRUITING

CHU de Nancy - Brabois

Nancy, France, France

RECRUITING

CHU d'Amiens

Amiens, France

RECRUITING

CHU d'Angers

Angers, France

RECRUITING

CH d Avignon - Hopital Henri Duffaut

Avignon, France

RECRUITING

CH de la Côte Basque - Hôpital de Bayonne

Bayonne, France

RECRUITING

Institut Bergonié

Bordeaux, France

RECRUITING

CHU de Caen - Côte de Nacre - IHBN

Caen, France

RECRUITING

CH Métropole Savoie

Chambéry, France

RECRUITING

CHU de Clermont Ferrand - Estaing

Clermont-Ferrand, France

RECRUITING

APHP - Hôpital Henri Mondor

Créteil, France

RECRUITING

CHU de Dijon BOURGOGNE - Hôpital François Mitterand

Dijon, France

RECRUITING

CH de Dunkerque

Dunkirk, France

RECRUITING

CHD de Vendée

La Roche-sur-Yon, France

RECRUITING

CHU de Grenoble - Hôpital Albert Michallon

La Tronche, France

RECRUITING

Ch de Versailles - Hopital Andre Mignot

Le Chesnay, France

RECRUITING

CH du Mans

Le Mans, 72000, France

RECRUITING

CHRU de Lille - Hôpital Claude Hurriez

Lille, France

RECRUITING

Hôpital Saint Vincent-De-Paul

Lille, France

RECRUITING

Chu de Limoges - Hopital Dupuytren

Limoges, France

RECRUITING

Centre Leon Berard

Lyon, 69373, France

RECRUITING

Chu de Meaux

Meaux, France

RECRUITING

CHU de Montpellier

Montpellier, France

RECRUITING

CH de Mulhouse

Mulhouse, France

RECRUITING

CHU de Nantes - Hôtel Dieu

Nantes, France

RECRUITING

CHU de Nîmes

Nîmes, France

RECRUITING

CHR d'Orléans

Orléans, France

RECRUITING

APHP - Hopital Necker

Paris, France

RECRUITING

APHP - Hôpital de la Pitié Salpétrière

Paris, France

RECRUITING

APHP - Hôpital Saint Antoine

Paris, France

RECRUITING

APHP - Hôpital Saint Louis

Paris, France

RECRUITING

CH de Perpignan

Perpignan, France

RECRUITING

CHU de Bordeaux - Hôpital Haut Lévêque - Centre François Magendie

Pessac, France

RECRUITING

CH de Périgueux

Périgueux, France

RECRUITING

Centre Hospitalier Lyon Sud

Pierre-Bénite, France

RECRUITING

CHU de Poitiers - Hôpital de La Milétrie

Poitiers, France

RECRUITING

Centre Hospitalier Annecy Genevois

Pringy, France

RECRUITING

CHU de Reims

Reims, France

RECRUITING

CHU de Rennes - Hôpital de Pontchaillou

Rennes, France

RECRUITING

Centre Henri Becquerel

Rouen, France

RECRUITING

Institut de Cancérologie et d'Hématologie Universitaire de Saint-Étienne

Saint-Etienne, France

RECRUITING

Institut de Cancerologie Strasbourg Europe

Strasbourg, France

RECRUITING

Institut Universitaire du Cancer de Toulouse - Oncopole

Toulouse, 31100, France

RECRUITING

CH de Bretagne Atlantique - Hopital Chubert

Vannes, France

RECRUITING

Charite Universitat Smedizin Berlin

Berlin, Germany

RECRUITING

GEORG-AUGUST-UNIV, GOETTINGEN - Klinik fur Haematologie und Medizini

Goettigen, Germany

RECRUITING

Universitatsklinikum Halle (Saale)

Halle, Germany

RECRUITING

UNIVERSITAT LEIPZIG - Klinik fur Hamatologie, Zelltherapie und Hamostaseo

Leipzig, Germany

RECRUITING

UNIVERSITATSKLINIKUM REGENSBURG - Klinik für Innere Medizin III

Regensburg, Germany

RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, Spain

NOT YET RECRUITING

Hospital Universitario Fundacion Jimenez Diaz - Hematologia

Madrid, Spain

RECRUITING

Hospital Universitario Marqués de Valdecilla

Santander, Spain

NOT YET RECRUITING

Hospital Clínico Universitario de Valencia

Valencia, Spain

NOT YET RECRUITING

Related Publications (1)

• Cheminant M, Lhermitte L, Bruneau J, Sicard H, Bonnafous C, Touzart A, Bourbon E, Ortonne N, Genestier L, Gaulard P, Palmic P, Suarez F, Frenzel L, Naveau L, Bazarbachi A, Dussiot M, Waast L, Avettand-Fenoel V, Brouzes C, Pique C, Lepelletier Y, Asnafi V, Marcais A, Hermine O. KIR3DL2 contributes to the typing of acute adult T-cell leukemia and is a potential therapeutic target. Blood. 2022 Sep 29;140(13):1522-1532. doi: 10.1182/blood.2022016765.

  PMID: 35687761 DERIVED

MeSH Terms

Conditions

Lymphoma, T-Cell, Peripheral; Recurrence; Lymphoma, T-Cell

Interventions

Gemcitabine; Oxaliplatin

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals

Study Officials

• Morgane Cheminant

  Lymphoma Study Association

  STUDY CHAIR

Central Study Contacts

Baptiste LAVERROUX

CONTACT

+33 4 27 01 27 18; kilt@lysarc.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2021
• First Posted: August 2, 2021
• Study Start: October 5, 2021
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): April 30, 2028
• Last Updated: April 20, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (43); DE (5); ES (4); BE (12)