Informations générales (source: ClinicalTrials.gov)
A Randomized Non Comparative Phase II Study of Lacutamab with GemOx Versus GemOx Alone in Relapsed/refractory Patients with Peripheral T-cell Lymphoma
Interventional
Phase 2
The Lymphoma Academic Research Organisation (Voir sur ClinicalTrials)
octobre 2021
janvier 2028
05 avril 2025
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).
Etablissements
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| AP-HP - Hôpital Necker-Enfants Malades | Morgane Cheminant, MD | Contact (sur clinicalTrials) | |||
| AP-HP - Hôpital Saint Antoine | Laure Ricard, MD | Contact (sur clinicalTrials) | |||
| CH DE VERSAILLES SITE ANDRE MIGNOT | Hassan FARHAT, MD | Contact (sur clinicalTrials) | |||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| APHP - Hôpital de la Pitié Salpétrière - Paris - France | Adrien GRENIER, MD | Contact (sur clinicalTrials) | |||
| APHP - Hôpital Henri Mondor - Créteil - France | François LEMONNIER, MD | Contact (sur clinicalTrials) | |||
| APHP - Hôpital Saint Louis - Paris - France | Catherine THIEBLEMONT, Pr | Contact (sur clinicalTrials) | |||
| Centre Henri Becquerel - Rouen - France | Olivier CAMUS, MD | Contact (sur clinicalTrials) | |||
| Centre Hospitalier Annecy Genevois - Pringy - France | Nicolas Daguindau, MD | Contact (sur clinicalTrials) | |||
| Centre Hospitalier Lyon Sud - Pierre Bénite - France | Emmanuel BACHY, Pr | Contact (sur clinicalTrials) | |||
| Centre Leon Berard - 69373 - Lyon - France | Yann GUILLERMIN, MD | Contact (sur clinicalTrials) | |||
| CH d Avignon - Hopital Henri Duffaut - Avignon - France | Borhane SLAMA, MD | Contact (sur clinicalTrials) | |||
| CH de Bretagne Atlantique - Hopital Chubert - Vannes - France | Antoine BONNET, MD | Contact (sur clinicalTrials) | |||
| CH de Dunkerque - Dunkerque - France | Sarah BARBIEUX, Dr | Contact (sur clinicalTrials) | |||
| CH de la Côte Basque - Hôpital de Bayonne - Bayonne - France | Sophie BERNARD, MD | Contact (sur clinicalTrials) | |||
| CH de Mulhouse - Mulhouse - France | Mathilde LAMARQUE, MD | Contact (sur clinicalTrials) | |||
| CH de Périgueux - Périgueux - France | Claire CALMETTES, MD | Contact (sur clinicalTrials) | |||
| CH de Perpignan - Perpignan - France | Sara BURCHERI, MD | Contact (sur clinicalTrials) | |||
| CH du Mans - 72000 - Le Mans - France | Kamel LARIBI, MD | Contact (sur clinicalTrials) | |||
| CH Métropole Savoie - Chambéry - France | Arthur DONY, Dr | Contact (sur clinicalTrials) | |||
| CHD de Vendée - La Roche-sur-Yon - France | Stéphane VIGOUROUX, MD | Contact (sur clinicalTrials) | |||
| CHR d'Orléans - Orleans - France | Marlène OCHMANN, MD | Contact (sur clinicalTrials) | |||
| CHRU de Lille - Hôpital Claude Hurriez - Lille - France | Franck MORSCHHAUSER, Pr | Contact (sur clinicalTrials) | |||
| CHU d'Amiens - Amiens - France | Pierre MOREL, MD | Contact (sur clinicalTrials) | |||
| CHU d'Angers - Angers - France | Aline CLAVERT, MD | Contact (sur clinicalTrials) | |||
| CHU de Bordeaux - Hôpital Haut Lévêque - Centre François Magendie - Pessac - France | Kamal BOUABDALLAH, MD | Contact (sur clinicalTrials) | |||
| CHU de Caen - Côte de Nacre - IHBN - Caen - France | Ghandi DAMAJ, MD | Contact (sur clinicalTrials) | |||
| CHU de Clermont Ferrand - Estaing - Clermont-Ferrand - France | Olivier TOURNILHAC, MD | Contact (sur clinicalTrials) | |||
| CHU de Dijon BOURGOGNE - Hôpital François Mitterand - Dijon - France | Olivier CASASNOVAS, MD | Contact (sur clinicalTrials) | |||
| CHU de Grenoble - Hôpital Albert Michallon - La Tronche - France | Sylvain CARRAS, MD | Contact (sur clinicalTrials) | |||
| Chu de Limoges - Hopital Dupuytren - Limoges - France | Julie ABRAHAM, MD | Contact (sur clinicalTrials) | |||
| Chu de Meaux - Meaux - France | Wajed ABARAH - ATASI, MD | Contact (sur clinicalTrials) | |||
| CHU de Montpellier - Montpellier - France | Charles HERBAUX, MD | Contact (sur clinicalTrials) | |||
| CHU de Nancy - Brabois - Nancy - France | Pierre FEUGIER, MD | Contact (sur clinicalTrials) | |||
| CHU de Nantes - Hôtel Dieu - Nantes - France | Thomas GASTINNE, MD | Contact (sur clinicalTrials) | |||
| CHU de Nîmes - Nîmes - France | Agathe WAULTIER RASCALOU, MD | Contact (sur clinicalTrials) | |||
| CHU de Poitiers - Hôpital de La Milétrie - Poitiers - France | Stéphanie GUIDEZ, MD | Contact (sur clinicalTrials) | |||
| CHU de Reims - Reims - France | Eric DUROT, MD | Contact (sur clinicalTrials) | |||
| CHU de Rennes - Hôpital de Pontchaillou - Rennes - France | Roch HOUOT, Pr | Contact (sur clinicalTrials) | |||
| Hôpital Saint Vincent-De-Paul - Lille - France | Sandy AMORIM, MD | Contact (sur clinicalTrials) | |||
| Institut Bergonié - Bordeaux - France | Fontanet BIJOU, Pr | Contact (sur clinicalTrials) | |||
| Institut de Cancérologie et d'Hématologie Universitaire de Saint-Étienne - Saint-Étienne - France | Ludovic FOUILLET, MD | Contact (sur clinicalTrials) | |||
| Institut de Cancerologie Strasbourg Europe - Strasbourg - France | Luc FORNECKER, Pr | Contact (sur clinicalTrials) | |||
| Institut Universitaire du Cancer de Toulouse - Oncopole - 31100 - Toulouse - France | Loïc YSEBAERT, MD | Contact (sur clinicalTrials) | |||
Critères
Tous
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
-
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
-
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