Study of Lacutamab in Peripheral T-cell Lymphoma

Peripheral T Cell Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04984837
• Other study ID #: KILT
• Status: Recruiting
• Phase: Phase 2
• Start date: October 5, 2021
• Est. completion date: January 30, 2027

Study information

• Verified date: December 2023
• Source: The Lymphoma Academic Research Organisation
• Contact: Baptiste LAVERROUX
• Phone: +33 4 27 01 27 18
• Email: kilt[@]lysarc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 56
• Est. completion date: January 30, 2027
• Est. primary completion date: January 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Peripheral
• Peripheral T Cell Lymphoma
• Recurrence
• Relapse/Recurrence

Intervention

Drug:
• Lacutamab
750 mg/IV
• Gemcitabine
1000 mg/m²
• Oxaliplatine
100 mg/m²

Locations

Country	Name	City	State
Belgium	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	HELORA - Hôpital de La LouvièreSite Jolimont	Haine-Saint-Paul
Belgium	CHU de LIEGE - Domaine Sart Tilman	Liège
Belgium	Clinique CHC MontLégia	Liège
Belgium	CHR Verviers	Verviers
Belgium	CHU Dinant Godinne - UCL Namur - YVOIR	Yvoir
France	CHU d'Amiens	Amiens
France	CHU d'Angers	Angers
France	CH d Avignon - Hopital Henri Duffaut	Avignon
France	CH de la Côte Basque - Hôpital de Bayonne	Bayonne
France	Institut Bergonié	Bordeaux
France	CHU de Caen - Côte de Nacre - IHBN	Caen
France	CH Métropole Savoie	Chambéry
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	CHD de Vendée	La Roche-sur-Yon
France	CHU de Grenoble - Hôpital Albert Michallon	La Tronche
France	Ch de Versailles - Hopital Andre Mignot	Le Chesnay
France	CH du Mans	Le Mans
France	CHRU de Lille - Hôpital Claude Hurriez	Lille
France	Hôpital Saint Vincent-De-Paul	Lille
France	Chu de Limoges - Hopital Dupuytren	Limoges
France	Centre Leon Berard	Lyon
France	Chu de Meaux	Meaux
France	CHU de Montpellier	Montpellier
France	CH de Mulhouse	Mulhouse
France	CHU de Nancy - Brabois	Nancy
France	CHU de Nantes - Hôtel Dieu	Nantes
France	CHU de Nîmes	Nîmes
France	CHR d'Orléans	Orleans
France	APHP - Hôpital de la Pitié Salpétrière	Paris
France	APHP - Hopital Necker	Paris
France	APHP - Hôpital Saint Antoine	Paris
France	APHP - Hôpital Saint Louis	Paris
France	CH de Périgueux	Périgueux
France	CH de Perpignan	Perpignan
France	CHU de Bordeaux - Hôpital Haut Lévêque - Centre François Magendie	Pessac
France	Centre Hospitalier Lyon Sud	Pierre Bénite
France	CHU de Poitiers - Hôpital de La Milétrie	Poitiers
France	Centre Hospitalier Annecy Genevois	Pringy
France	CHU de Reims	Reims
France	CHU de Rennes - Hôpital de Pontchaillou	Rennes
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
Germany	Charite Universitat Smedizin Berlin	Berlin
Germany	GEORG-AUGUST-UNIV, GOETTINGEN - Klinik fur Haematologie und Medizini	Goettigen
Germany	Universitatsklinikum Halle (Saale)	Halle
Germany	UNIVERSITAT LEIPZIG - Klinik fur Hamatologie, Zelltherapie und Hamostaseo	Leipzig
Germany	UNIVERSITATSKLINIKUM REGENSBURG - Klinik für Innere Medizin III	Regensburg
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitario Fundacion Jimenez Diaz - Hematologia	Madrid
Spain	Hospital Universitario Marqués de Valdecilla	Santander
Spain	Hospital Clínico Universitario de Valencia	Valencia

Sponsors (2)

Lead Sponsor	Collaborator
The Lymphoma Academic Research Organisation	Innate Pharma

Countries where clinical trial is conducted

Belgium,  France,  Germany,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	median modified progression-free survival (mPFS) - CT-based	time from randomization until one of the following events occurs, whichever comes first: Disease progression (PD); Administration of any additional unplanned anti-lymphoma treatment (except allogeneic or autologous hematopoietic cell transplantations (HCT)); Relapse after achievement of CR; Death due to any cause. PD and relapse will be evaluated according to Lugano 2014 criteria (CT-based).	5,5 years.
Secondary	median modified progression-free survival (mPFS) - PET-based		5,5 years.
Secondary	Number of Adverse Events		5,5 years.
Secondary	overall survival (OS)		5,5 years.
Secondary	complete response rate (CRR) Lugano 2014 criteria (CT-based)		5,5 years.
Secondary	complete response rate (CRR) Lugano 2014 criteria (PET-based)		5,5 years.
Secondary	overall response rate (ORR) Lugano 2014 criteria (CT-based)		5,5 years.
Secondary	overall response rate (ORR) Lugano 2014 criteria (PET-based)		5,5 years.
Secondary	response rate assessed by Deauville criteria		5,5 years.
Secondary	duration of response (DOR),	Disease progression (PD); Administration of any additional unplanned anti-lymphoma treatment (except allogeneic or autologous hematopoietic cell transplantations (HCT)); Relapse after achievement of CR; Death due to any cause	5,5 years.
Secondary	rate of patients proceeding to allogenic stem cell transplantation		5,5 years.
Secondary	Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax)		1 month (1 cycle)
Secondary	Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough)		1 month (1 cycle)
Secondary	Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax)		2 months (2 cycles)
Secondary	Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough)		2 months (2 cycles)
Secondary	Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax)		3 months (3 cycles)
Secondary	Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough)		3 months (3 cycles)
Secondary	Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax)		7 months (7 cycles)
Secondary	Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough)		7 months (7 cycles)
Secondary	Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax)		9 months (9 cycles)
Secondary	Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough)		9 months (9 cycles)
Secondary	Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax)		15 months (15 cycles)
Secondary	Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough)		15 months (15 cycles)
Secondary	Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax)		26 months (26 cycles)
Secondary	Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough)		26 months (26 cycles)
Secondary	Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax)		29 months (29 cycles)
Secondary	Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough)		29 months (29 cycles)
Secondary	Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx		1 month (1 cycle)
Secondary	Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx		2 months (2 cycles)
Secondary	Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx		3 months (3 cycles)
Secondary	Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx		7 months (7 cycles)
Secondary	Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx		9 months (9 cycles)
Secondary	Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx		15 months (15 cycles)
Secondary	Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx		26 months
Secondary	Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx		29 months