KILT
Etude de phase II randomisée non comparative du lacutamab avec GemOx versus GemOx seul chez des patients en rechute/réfractaires atteints d'un lymphome périphérique à cellules T

Phase : II

Type d'essai : Académique / Institutionnel

Etat de l'essai : Ouvert

Objectif principal

L’étude vise à évaluer l’efficacité et la tolérance d’un traitement par lacutamab, un médicament expérimental, en association avec la chimiothérapie GemOx, en comparaison avec la chimiothérapie seule.

Résumé / Schéma de l'étude

Dans cette étude, un test recherchant le récepteur KIR3DL2 est tout d’abord réalisé pour les patients sollicités, à partir d’une biopsie. Seuls les patients dont les cellules tumorales expriment ce récepteur sont inclus dans l’étude.

Les patients sélectionnés sont répartis par tirage au sort entre deux groupes :
- Dans le premier groupe (Bras expérimental), les patients reçoivent le lacutamab associé à la chimiothérapie GemOx.
Le traitement est prévu pendant 6 cycles de 21 jours. Si le traitement s’avère efficace, le lacutamab est poursuivi seul. Il est alors administré toutes les 4 semaines, jusqu’à un maximum de 2 ans.
- Dans le second groupe (Bras témoin), les patients reçoivent la chimiothérapie GemOx seule.
Le traitement est prévu pendant 6 cycles de 21 jours.

À l’issue du traitement, les patients font l’objet d’une surveillance jusqu’à un maximum de 2 ans.
Le tirage au sort initial est conçu pour que deux fois plus de patients participent au premier groupe par rapport au second.

Critères d'inclusion

  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) :
    1. PTCL-NOS.
    2. PTCL-TFH (AITL, Follicular T-cell lymphoma, Nodal peripheral T-cell lymphoma with TFH phenotype).
    3. ALCL.
    4. ATL: acute- or lymphoma-type.
    5. HSTL.
    6. EATL.
    7. MEITL.
    8. NKT.
    9. 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.

Critères de non-inclusion

  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.
  5. Previous allogenic hematopoietic cell transplantation.
  6. 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).
  7. 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.
  8. Central nervous system or meningeal involvement by lymphoma.
  9. Any of the following laboratory abnormalities prior randomization :
    1. Absolute neutrophil count (ANC) < 1 G/L, unless neutropenia is related to PTCL.
    2. Platelet count < 75 G/L, unless thrombopenia is related to PTCL.
    3. Alkaline Phosphatases > 2.5 x LIN.
    4. Serum Glutamoyl-oxaloacetate Transferase (SGOT) /Alanine aminotransferase (AST) or Serum Glutamate Pyruvate Transaminase (SGPT)/Alanine aminotransferase (ALT) > 2.5 x LIN Bilirubin > 1.5 x LIN, unless SGOT/AST and SGPT/ALT > 2.5 x LIN or bilirubin elevated due to PTCL or hemolysis.
    5. Calculated creatinine clearance (MDRD or Cockcroft) < 40 mL/min.
  10. 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.
  11. 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.
  12. 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.
  13. Major surgery within 4 weeks before randomization.
  14. Pregnant or lactating females.

Calendrier prévisionnel

Lancement de l'étude : Juin 2021
Fin estimée des inclusions : Juin 2024
Nombre de aptients à inclure : 141

Etablissement(s) participant(s)

> Centre Hospitalier d'Avignon Henri Duffaut

(84) Vaucluse

Dr. Borhane SLAMA
Investigateur principal

Coordonnateur(s)

Pr. Franck MORSCHHAUSER

The Lymphoma Academic Research Organisation - LYSARC

Promoteur(s)

LYSARC (The Lymphoma Academic Research Organisation)

Dernière mise à jour le 04 août 2022