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Study of Lacutamab in Peripheral T-cell Lymphoma

Sponsor
The Lymphoma Academic Research Organisation (Other)
Overall Status
Recruiting
CT.gov ID
NCT04984837
Collaborator
Innate Pharma (Industry)
56
Enrollment
39
Locations
2
Arms
63.8
Anticipated Duration (Months)
1.4
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
56 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Oct 5, 2021
Anticipated Primary Completion Date :
Jan 30, 2025
Anticipated Study Completion Date :
Jan 30, 2027

Arms and Interventions

Arm Intervention/Treatment
Experimental: Lacutamab

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
750 mg/IV

Drug: Gemcitabine
1000 mg/m²

Drug: Oxaliplatine
100 mg/m²
Active Comparator: Standard of care

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

Drug: Gemcitabine
1000 mg/m²

Drug: Oxaliplatine
100 mg/m²

Outcome Measures

Primary Outcome Measures

  1. median modified progression-free survival (mPFS) - CT-based [5,5 years.]

    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).

Secondary Outcome Measures

  1. median modified progression-free survival (mPFS) - PET-based [5,5 years.]

  2. Number of Adverse Events [5,5 years.]

  3. overall survival (OS) [5,5 years.]

  4. complete response rate (CRR) Lugano 2014 criteria (CT-based) [5,5 years.]

  5. complete response rate (CRR) Lugano 2014 criteria (PET-based) [5,5 years.]

  6. overall response rate (ORR) Lugano 2014 criteria (CT-based) [5,5 years.]

  7. overall response rate (ORR) Lugano 2014 criteria (PET-based) [5,5 years.]

  8. response rate assessed by Deauville criteria [5,5 years.]

  9. duration of response (DOR), [5,5 years.]

    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

  10. rate of patients proceeding to allogenic stem cell transplantation [5,5 years.]

  11. Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax) [1 month (1 cycle)]

  12. Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough) [1 month (1 cycle)]

  13. Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax) [2 months (2 cycles)]

  14. Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough) [2 months (2 cycles)]

  15. Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax) [3 months (3 cycles)]

  16. Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough) [3 months (3 cycles)]

  17. Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax) [7 months (7 cycles)]

  18. Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough) [7 months (7 cycles)]

  19. Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax) [9 months (9 cycles)]

  20. Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough) [9 months (9 cycles)]

  21. Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax) [15 months (15 cycles)]

  22. Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough) [15 months (15 cycles)]

  23. Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax) [26 months (26 cycles)]

  24. Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough) [26 months (26 cycles)]

  25. Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax) [29 months (29 cycles)]

  26. Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough) [29 months (29 cycles)]

  27. Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx [1 month (1 cycle)]

  28. Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx [2 months (2 cycles)]

  29. Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx [3 months (3 cycles)]

  30. Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx [7 months (7 cycles)]

  31. Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx [9 months (9 cycles)]

  32. Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx [15 months (15 cycles)]

  33. Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx [26 months]

  34. Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx [29 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

  1. 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

  1. Pregnant or lactating females

Contacts and Locations

Locations

Site City State Country Postal Code
1 ZNA Stuivenberg Antwerpen Belgium
2 A. Z. Sint-Jan Bruges Belgium
3 Clinique Universitaire Saint LUC Brussels Belgium
4 Cliniques Universitaires de Bruxelles - Hôpital Erasme Bruxelles Belgium
5 Universitair Ziekenhuis Antwerpen Edegem Belgium
6 Hôpital Jolimont Haine-Saint-Paul Belgium
7 CH Liège Liège Belgium
8 CHRU Mont Godinne Yvoir Belgium
9 CHU Amiens - Hôpital Sud Amiens France
10 CHU d'Amiens Amiens France
11 CH d Avignon - Hopital Henri Duffaut Avignon France
12 CH de la Côte Basque Bayonne France 64109
13 CHRU Besançon - Hôpital Minjoz Besançon France
14 CH de Chambéry Chambéry France
15 CHU de Clermont Ferrand - Estaing Clermont-Ferrand France
16 APHP - Hôpital Henri Mondor Créteil France
17 CHU de Dijon Dijon France
18 CHU de Grenoble La Tronche France
19 Ch de Versailles - Hopital Andre Mignot Le Chesnay France
20 CH du Mans Le Mans France 72000
21 CHRU de Lille - Hôpital Claude Hurriez Lille France
22 Chu de Limoges - Hopital Dupuytren Limoges France
23 Centre Leon Berard Lyon France 69373
24 Chu de Meaux Meaux France
25 CHU de Montpellier Montpellier France
26 CH de Mulhouse Mulhouse France
27 CHU de Nancy - Brabois Nancy France 54511
28 CHU de Nantes - Hôtel Dieu Nantes France
29 APHP - Hopital Necker Paris France
30 APHP - Hôpital Saint Antoine Paris France
31 APHP - Hôpital Saint Louis Paris France
32 CHU de la Pitié Salpêtrière Paris France
33 Centre Francois Magendie Pessac France
34 Centre Hospitalier Lyon Sud Pierre Bénite France
35 CHU de Poitiers - Hôpital de La Milétrie Poitiers France
36 Centre Hospitalier Annecy Genevois Pringy France
37 CHU de Rennes - Hôpital de Pontchaillou Rennes France
38 Centre Henri Becquerel Rouen France
39 Institut Universitaire du Cancer de Toulouse - Oncopole Toulouse France 31100

Sponsors and Collaborators

  • The Lymphoma Academic Research Organisation
  • Innate Pharma

Investigators

  • Study Chair: Morgane Cheminant, Lymphoma Study Association

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
The Lymphoma Academic Research Organisation
ClinicalTrials.gov Identifier:
NCT04984837
Other Study ID Numbers:
  • KILT
First Posted:
Aug 2, 2021
Last Update Posted:
Aug 19, 2022
Last Verified:
Aug 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by The Lymphoma Academic Research Organisation
KIR3DL2
PTCL
T-cell Lymphoma
Additional relevant MeSH terms:
Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Recurrence
Gemcitabine
Oxaliplatin

Study Results

No Results Posted as of Aug 19, 2022