Kilt - a Randomized Non Comparative Phase Ii Study of Lacutamab with Gemox Versus Gemox Alone in Relapsed/Refractory Patients with Peripheral T-Cell Lymphoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Lysarc

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

28 Jan 2021 → ongoing

Decision date (initial)

2024-08-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-513252-15-00

EudraCT number

2020-003735-16

ClinicalTrials.gov

NCT04984837

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety

To evaluate the median modified progression-free survival (mPFS) of Lacutamab in patients treated with Gemcitabine-oxaliplatin (GemOx) at relapse followed by a Lacutamab maintenance, in relapsed/refractory (R/R) patients with KIR3DL2 positive PTCL-NOS, PTCL-TFH (including AITL, Follicular T-cell lymphoma, Nodal peripheral T-cell lymphoma with TFH phenotype), ALCL, ATL, HSTL, EATL, MEITL, NKT and ANKL.

Secondary objectives 5

1. To characterize the safety and tolerability of Lacutamab
2. To evaluate overall survival (OS)
3. To evaluated mPFS with PD and relapse evaluated according to Lugano 2014 criteria (PET-based)
4. To characterize the Pharmacokinetics of lacutamab with GemOx (for experimental arm only)
5. To evaluate the immunogenicity (Anti-Drug Antibodies (ADA)) of lacutamab with GemOx (for experimental arm only)

Conditions and MedDRA coding

IN RELAPSED/REFRACTORY PATIENTS WITH PERIPHERAL T-CELL LYMPHOMA

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. KIR3DL2-positive with at least 1% of tumor cells positivity, before randomization, based on central evaluation by IHC
2. Patients with histologically documented PTCL: o 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 comptabilized 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. 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 treatment
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
15. Patient covered by any social security system (France)
16. Patient who understands and speaks one of the country official languages

Exclusion criteria 20

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, vepeside (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 HCV (Patients who are positive for HCV antibody must be negative for HCV by PCR to be eligible for study participation)
8. 8. Known active hepatitis B (positive Ag HBs) (if latent HBV (positive anti-HBc), patients have to be treated with Entecavir (Baraclude ®) and HBV PCR should be performed every month to allow antiviral strategy adapatation)
9. Central nervous system or meningeal involvement by lymphoma
10. Any of the following laboratory abnormalities prior randomization: o Absolute neutrophil count (ANC) < 1 G/L, unless neutropenia is related to PTCL o Platelet count < 75 G/L, unless thrombopenia is related to PTCL o Alkaline Phosphatases > 2.5 x upper limit of normal (ULN) o Serum SGOT/AST or SGPT/ALT > 2.5 x ULN o Bilirubin > 1.5 x ULN, unless SGOT/AST and SGPT/ALT > 2.5 x ULN or bilirubin elevated due to PTCL or hemolysis o Calculated creatinine clearance (MDRD or Cockroft) < 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
16. Person deprived of his/her liberty by a judicial or administrative decision
17. Person hospitalized without consent
18. Adult person under legal protection
19. Adult person unable to provide informed consent because of intellectual impairment, any serious medical condition, laboratory abnormality or psychiatric illness
20. Extensive radiotherapy (e.g. whole pelvis, half spine) within 3 months before randomization

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. modified PFS (mPFS), defined as time from randomization until one of the following events occurs, whichever comes first: a) Disease progression (PD) b) Administration of any additional unplanned anti-lymphoma treatment (except allogeneic or autologous hematopoietic cell transplantations (HCT)) c) Relapse after achievement of CR or PR d) Death due to any cause.

Secondary endpoints 6

1. Response rates according to Lugano classification PET-based
2. Response rate assessed by Deauville criteria
3. Duration Of Response (DOR)
4. CR rate and ORR according to Lugano 2014 criteria (PET-based)
5. subgroup analyses of mPFS, ORR, DOR, OS by PTCL subtype based on previous treatment lines
6. rate of patients proceeding to allogenic stem cell transplantation

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Lysarc

Sponsor organisation

LYSARC

Address

2d Lyon Sud Batiment

City

Pierre Benite Cedex

Postcode

69495

Country

France

Scientific contact point

Organisation

LYSARC

Contact name

Anne VIOLA

Public contact point

Organisation

LYSARC

Contact name

Anne VIOLA

Locations

4 EU/EEA countries · 65 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 52 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications