Clinical trial NCT04984837: Study of Lacutamab in Peripheral T-cell Lymphoma
Official title: A Randomized Non Comparative Phase II Study of Lacutamab with GemOx Versus GemOx Alone in Relapsed/refractory Patients with Peripheral T-cell Lymphoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Peripheral T Cell Lymphoma
Relapse/Recurrence
Keywords: KIR3DL2
PTCL
T-cell Lymphoma
Lead sponsor: The Lymphoma Academic Research Organisation
Sponsor class: OTHER
Collaborators: name: Innate Pharma
First posted: 2021-08-02
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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 outcomes:
measure: median modified progression-free survival (mPFS) - CT-based
timeFrame: 5,5 years.
Secondary outcomes:
measure: median modified progression-free survival (mPFS) - PET-based
timeFrame: 5,5 years.
measure: Number of Adverse Events
timeFrame: 5,5 years.
measure: overall survival (OS)
timeFrame: 5,5 years.
measure: complete response rate (CRR) Lugano 2014 criteria (CT-based)
timeFrame: 5,5 years.
measure: complete response rate (CRR) Lugano 2014 criteria (PET-based)
timeFrame: 5,5 years.
measure: overall response rate (ORR) Lugano 2014 criteria (CT-based)
timeFrame: 5,5 years.
measure: overall response rate (ORR) Lugano 2014 criteria (PET-based)
timeFrame: 5,5 years.
measure: response rate assessed by Deauville criteria
timeFrame: 5,5 years.
measure: duration of response (DOR),
timeFrame: 5,5 years.
measure: rate of patients proceeding to allogenic stem cell transplantation
timeFrame: 5,5 years.
measure: Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax)
timeFrame: 1 month (1 cycle)
measure: Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough)
timeFrame: 1 month (1 cycle)
measure: Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax)
timeFrame: 2 months (2 cycles)
measure: Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough)
timeFrame: 2 months (2 cycles)
measure: Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax)
timeFrame: 3 months (3 cycles)
measure: Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough)
timeFrame: 3 months (3 cycles)
measure: Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax)
timeFrame: 7 months (7 cycles)
measure: Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough)
timeFrame: 7 months (7 cycles)
measure: Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax)
timeFrame: 9 months (9 cycles)
measure: Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough)
timeFrame: 9 months (9 cycles)
measure: Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax)
timeFrame: 15 months (15 cycles)
measure: Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough)
timeFrame: 15 months (15 cycles)
measure: Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax)
timeFrame: 26 months (26 cycles)
measure: Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough)
timeFrame: 26 months (26 cycles)
measure: Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax)
timeFrame: 29 months (29 cycles)
measure: Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough)
timeFrame: 29 months (29 cycles)
measure: Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx
timeFrame: 1 month (1 cycle)
measure: Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx
timeFrame: 2 months (2 cycles)
measure: Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx
timeFrame: 3 months (3 cycles)
measure: Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx
timeFrame: 7 months (7 cycles)
measure: Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx
timeFrame: 9 months (9 cycles)
measure: Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx
timeFrame: 15 months (15 cycles)
measure: Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx
timeFrame: 26 months
measure: Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx
timeFrame: 29 months
Other outcomes:
Locations:
city: Anderlecht
country: Belgium
facility: Institut Jules Bordet
city: Antwerpen
country: Belgium
facility: ZNA Cadix
city: Bruges
country: Belgium
facility: A. Z. Sint-Jan
city: Brussels
country: Belgium
facility: Cliniques universitaires Saint-Luc - Université catholique de Louvain
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires de Bruxelles - Hôpital Erasme
city: Charleroi
country: Belgium
facility: Grand Hôpital de Charleroi
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Haine-Saint-Paul
country: Belgium
facility: HELORA - Hôpital de La LouvièreSite Jolimont
city: Liège
country: Belgium
facility: CHU de LIEGE - Domaine Sart Tilman
city: Liège
country: Belgium
facility: Clinique CHC MontLégia
city: Verviers
country: Belgium
facility: CHR Verviers
city: Yvoir
country: Belgium
facility: CHU Dinant Godinne - UCL Namur - YVOIR
city: Amiens
country: France
facility: CHU d'Amiens
city: Angers
country: France
facility: CHU d'Angers
city: Avignon
country: France
facility: CH d Avignon - Hopital Henri Duffaut
city: Bayonne
country: France
facility: CH de la Côte Basque - Hôpital de Bayonne
city: Bordeaux
country: France
facility: Institut Bergonié
city: Caen
country: France
facility: CHU de Caen - Côte de Nacre - IHBN
city: Chambéry
country: France
facility: CH Métropole Savoie
city: Clermont-Ferrand
country: France
facility: CHU de Clermont Ferrand - Estaing
city: Créteil
country: France
facility: APHP - Hôpital Henri Mondor
city: Dijon
country: France
facility: CHU de Dijon BOURGOGNE - Hôpital François Mitterand
city: Dunkerque
country: France
facility: CH de Dunkerque
city: La Roche-sur-Yon
country: France
facility: CHD de Vendée
city: La Tronche
country: France
facility: CHU de Grenoble - Hôpital Albert Michallon
city: Le Chesnay
country: France
facility: Ch de Versailles - Hopital Andre Mignot
city: Le Mans
country: France
facility: CH du Mans
city: Lille
country: France
facility: CHRU de Lille - Hôpital Claude Hurriez
city: Lille
country: France
facility: Hôpital Saint Vincent-De-Paul
city: Limoges
country: France
facility: Chu de Limoges - Hopital Dupuytren
city: Lyon
country: France
facility: Centre Leon Berard
city: Meaux
country: France
facility: Chu de Meaux
city: Montpellier
country: France
facility: CHU de Montpellier
city: Mulhouse
country: France
facility: CH de Mulhouse
city: Nancy
country: France
facility: CHU de Nancy - Brabois
city: Nantes
country: France
facility: CHU de Nantes - Hôtel Dieu
city: Nîmes
country: France
facility: CHU de Nîmes
city: Orleans
country: France
facility: CHR d'Orléans
city: Paris
country: France
facility: APHP - Hopital Necker
city: Paris
country: France
facility: APHP - Hôpital de la Pitié Salpétrière
city: Paris
country: France
facility: APHP - Hôpital Saint Antoine
city: Paris
country: France
facility: APHP - Hôpital Saint Louis
city: Perpignan
country: France
facility: CH de Perpignan
city: Pessac
country: France
facility: CHU de Bordeaux - Hôpital Haut Lévêque - Centre François Magendie
city: Pierre Bénite
country: France
facility: Centre Hospitalier Lyon Sud
city: Poitiers
country: France
facility: CHU de Poitiers - Hôpital de La Milétrie
city: Pringy
country: France
facility: Centre Hospitalier Annecy Genevois
city: Périgueux
country: France
facility: CH de Périgueux
city: Reims
country: France
facility: CHU de Reims
city: Rennes
country: France
facility: CHU de Rennes - Hôpital de Pontchaillou
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint-Étienne
country: France
facility: Institut de Cancérologie et d'Hématologie Universitaire de Saint-Étienne
city: Strasbourg
country: France
facility: Institut de Cancerologie Strasbourg Europe
city: Toulouse
country: France
facility: Institut Universitaire du Cancer de Toulouse - Oncopole
city: Vannes
country: France
facility: CH de Bretagne Atlantique - Hopital Chubert
city: Berlin
country: Germany
facility: Charite Universitat Smedizin Berlin
city: Goettigen
country: Germany
facility: GEORG-AUGUST-UNIV, GOETTINGEN - Klinik fur Haematologie und Medizini
city: Halle
country: Germany
facility: Universitatsklinikum Halle (Saale)
city: Leipzig
country: Germany
facility: UNIVERSITAT LEIPZIG - Klinik fur Hamatologie, Zelltherapie und Hamostaseo
city: Regensburg
country: Germany
facility: UNIVERSITATSKLINIKUM REGENSBURG - Klinik für Innere Medizin III
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz - Hematologia
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
Study officials:
affiliation: Lymphoma Study Association
name: Morgane Cheminant
role: STUDY_CHAIR
References:
citation: 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.