Study of Brentuximab Vedotin in Patients With R/R PTCL Treated With Gemcitabine

NCT ID: NCT03496779

Last Updated: 2025-07-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 71 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-04-10
• Study Completion Date: 2022-10-08

Brief Summary

This study is an open label, multicenter phase 2 study. The primary objective of the study is to determine the efficacy of brentuximab vedotin in patients treated by gemcitabine for relapsed or refractory peripheral T-cell lymphoma in term of overall response rate assessed after 4 cycles of treatment according to the international response criteria for malignant lymphoma (Lugano Classification 2014 - CT-Based Response).

Detailed Description

Currently, there is no standard treatment for patients with recurrent or refractory peripheral T-cell lymphoma who relapse after a first line of cyclophosphamide, hydroxydaunomycin, oncovin, and prednisone (CHOP) treatment.

Chemotherapies such as gemcitabine are used as monotherapy but the results alone are insufficient. In addition, there is no approved monotherapy in the European Union, with the exception of brentuximab vedotin in refractory or recurrent large systemic anaplastic lymphomas.

Stem cell transplantation may be an option for patients who respond to a second line of treatment or a subsequent line of treatment, but conditions for being eligible for transplantation, including long-term remission, are infrequent.

Brentuximab vedotin (BV) is a targeted treatment directed against a protein, cluster of differentiation antigen 30 (CD30), present on the surface of lymphoma cells. It allows chemotherapy to enter directly into the lymphoma cell. The CD30 protein is variably expressed in patients with relapsed or refractory T-cell lymphoma; about 50% of patients have significant expression.

Data from clinical studies with brentuximab vedotin suggest that the addition of this treatment to gemcitabine may be more successful than gemcitabine alone.

The main hypothesis is a 15% increase in responder patients after 4 cycles of treatment with brentuximab vedotin and gemcitabine. The main objective of the study is therefore to determine the overall response rate after 4 cycles of treatment according to the criteria of Lugano 2014 (response based on CT-scan).

The secondary objectives will focus on the efficacy of brentuximab vedotin: complete response rate, response time for responder patients, time to failure of treatment, time to next treatment and overall survival, efficacy of brentuximab vedotin maintenance: survival progression-free, response time, overall survival, overall response rate based on positron emission tomography (PET)-scan and brentuximab vedotin toxicity in patients treated with gemcitabine and in maintenance therapy.

The duration of the study is estimated to be 4.5 years including follow-up with an estimated recruitment period of 1.5 years. 70 patients will be enrolled.

Conditions

Refractory Peripheral T-Cell Lymphoma; Relapsed Peripheral T-Cell Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental

Patients treated with gemcitabine will receive Brentuximab Vedotin-induction for 4 cycles of induction.

Patients who will obtain partial or complete response and who will be eligible for transplant will receive autologous or allogeneic stem cell transplantation.

Patients who will obtain partial or complete response and who will not be eligible for transplant will receive maintenance therapy with Brentuximab Vedotin-maintenance every 3 weeks for 12 infusions.

Group Type: EXPERIMENTAL

Brentuximab Vedotin - induction

Intervention Type: DRUG

Brentuximab vedotin 1.8 mg/kg at D8 of a 28-day cycle - 4 cycles = 16 weeks for combined chemotherapy

Gemcitabine

Intervention Type: DRUG

Gemcitabine 1000 mg/m² at D1 and D15 of a 28-day cycle - 4 cycles = 16 weeks for combined chemotherapy

Brentuximab Vedotin - maintenance

Intervention Type: DRUG

Patients who will obtain partial or complete response and who will not be eligible for transplant will receive maintenance therapy with brentuximab vedotin every 3 weeks for 12 infusions.

Brentuximab vedotin 1.8 mg/kg at D1 of a 21-day cycle - 12 cycles = 36 weeks for maintenance therapy

autologous or allogeneic stem cell transplantation

Intervention Type: PROCEDURE

Patients who will obtain partial or complete response and who will be eligible for transplant will receive autologous or allogeneic stem cell transplantation

Interventions

Brentuximab Vedotin - induction

Brentuximab vedotin 1.8 mg/kg at D8 of a 28-day cycle - 4 cycles = 16 weeks for combined chemotherapy

Intervention Type: DRUG

Gemcitabine

Gemcitabine 1000 mg/m² at D1 and D15 of a 28-day cycle - 4 cycles = 16 weeks for combined chemotherapy

Intervention Type: DRUG

Brentuximab Vedotin - maintenance

Patients who will obtain partial or complete response and who will not be eligible for transplant will receive maintenance therapy with brentuximab vedotin every 3 weeks for 12 infusions.

Brentuximab vedotin 1.8 mg/kg at D1 of a 21-day cycle - 12 cycles = 36 weeks for maintenance therapy

Intervention Type: DRUG

autologous or allogeneic stem cell transplantation

Patients who will obtain partial or complete response and who will be eligible for transplant will receive autologous or allogeneic stem cell transplantation

Intervention Type: PROCEDURE

Other Intervention Names

Adcetris; Gemzar; Adcetris

Eligibility Criteria

Inclusion Criteria

• Males and females of 18 years to 80 years of age;
• Understand and voluntarily sign an informed consent document prior to any study related assessment or procedure;
• Patients able to adhere to the study visit schedule and protocol requirements;
• Patients with histologically proven, CD30 positive (at least 5% of cells according to local examination) peripheral T-cell lymphoma (PTCL) according to the 2016 World Health Organization (WHO) classification for whom gemcitabine treatment is expected. A biopsy at relapse is highly recommended;
• Patients who have evidence of relapsed disease after at least one line (and no more than three lines) of treatment or who were refractory to a first or subsequent line of treatment;
• Patients with Ann Arbor stage I - IV;
• Patients with Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2;
• Patients with at least one measurable disease, i.e. one nodal or extra-nodal lesion of 1.5 cm or more;
• Negative pregnancy test for females of childbearing potential (FCBP);
• Female patients of child bearing potential must use an effective method of birth control (i.e. hormonal contraceptive, intrauterine device, diaphragm with spermicide, condom with spermicide or abstinence) during treatment period and 6 months thereafter.
• Males must use an effective method of birth control during treatment period and 6 months thereafter.

Exclusion Criteria

• Any significant medical condition or laboratory abnormality unrelated to PTCL, or psychiatric illness that would prevent the patient from participating in the study and from signing the informed consent form;
• Any condition that confounds the ability to interpret data from the study;
• Other types of lymphomas, e.g. B-cell lymphoma;
• Central nervous system and/or meningeal involvement by PTCL;
• Signs or symptoms of Progressive Multifocal Leukoencephalopathy;
• Preexistent peripheral neuropathy ≥ grade 2, whatever the cause;
• Contraindication to any drug contained in the chemotherapy regimen;
• Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximab vedotin;
• Subjects with HIV or HTLV1 positivity;
• Subjects with active hepatitis B or C. Chronic carriers of hepatitis B without hepatitis B virus (HBV) DNA positive blood are eligible. Subjects with non-active hepatitis C (with normal transaminases) are eligible;
• Chronic or acute, clinically significant, untreated bacterial, viral or fungal infection;
• Any of the following laboratory abnormalities:

1. Absolute neutrophil count (ANC) < 1500 cells/mm3 (1.5 x 109/L);

2. Platelet count <75,000/mm3 (75 x 109/L);

3. Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 3.0 x upper limit of normal (ULN). AST or ALT may be elevated up to 5 x ULN if their elevation can be ascribed to the presence of hematologic/solid tumor in the liver;

4. Serum total bilirubin > 1.5 x ULN;

5. Serum lipase level > 2 x ULN;

6. Serum creatinine > 2.0 mg/dL and/or creatinine clearance or calculated creatinine clearance < 40 mL/minute;

7. Hemoglobin < 8g/dL;

• Active malignancies other than PTCL requiring systemic treatment;
• Previous treatment with brentuximab vedotin;
• Previous treatment with gemcitabine;
• Pregnant or lactating females or women of childbearing potential not willing to use an adequate method of birth control for the duration of the study;
• Known history of any of the following cardiovascular conditions:

1. Myocardial infarction within 2 years of enrollment

2. New York Heart Association (NYHA) Class III or IV heart failure

3. Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure (CHF), angina, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities

4. Recent evidence (within 6 months before first dose of study drug) of a left-ventricular ejection fraction <50%

• Patients that have not completed any prior treatment chemotherapy and/or other investigational agents within at least 5 half-lives of last dose of that prior treatment;
• Diagnosed or treated for another malignancy within 3 years before the first dose or previously diagnosed with another malignancy and have evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Lymphoma Academic Research Organisation

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Richard DELARUE, MD

Role: STUDY_CHAIR

APHP - Hôpital Necker

Olivier TOURNILHAC, MD

Role: STUDY_CHAIR

CHU Estaing - Clermont Ferrant

Locations

ZNA Stuivenberg

Antwerp, , Belgium

A. Z. Sint-Jan

Bruges, , Belgium

Clinique Universitaire Saint LUC

Brussels, , Belgium

Institut Jules Bordet

Brussels, , Belgium

ULB Hôpital Erasme

Brussels, , Belgium

UZ Gent

Ghent, , Belgium

CHU de Liege

Liège, , Belgium

CHU UCL Namur

Yvoir, , Belgium

IHBN - CHU Cote de Nacre

Amiens, , France

CHU d'Amiens

Amiens, , France

CHU Angers

Angers, , France

CH d'Avignon - Hôpital Henri Dufaut

Avignon, , France

CH Côte Basque

Bayonne, , France

CHU de Besançon - Hôpital Jean Minjoz

Besançon, , France

CH Chambéry

Chambéry, , France

CHU d'Estaing

Clermont-Ferrand, , France

APHP - Hopital Henri Mondor

Créteil, , France

CHU de Dijon - Hôpital le Bocage

Dijon, , France

CHU Grenoble

Grenoble, , France

CH de Versailles - Hopital André Mignot

Le Chesnay, , France

CH du Mans

Le Mans, , France

CHRU de Lille - Hôpital Claude Huriez

Lille, , France

CHU de Limoges

Limoges, , France

Centre Leon Berard

Lyon, , France

Centre Hospitalier Annecy Genevois

Metz-Tessy, , France

CH Saint-Eloi

Montpellier, , France

CH de Mulhouse Sud Alsace

Mulhouse, , France

CHU Nancy - Brabois

Nancy, , France

CHU de Nantes - Hôtel Dieu

Nantes, , France

APHP - Hôpital Necker

Paris, , France

APHP - Hôpital Saint Louis

Paris, , France

Centre François Magendie - Hôpital du Haut Lévêque

Pessac, , France

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

CHU de Poitiers - Hôpital de la Milétrie

Poitiers, , France

CHU De Rennes

Rennes, , France

Centre Henri BECQUEREL

Rouen, , France

CHU de Toulouse

Toulouse, , France

CHRU de Tours

Tours, , France

CH de Valenciennes

Valenciennes, , France

Countries

Belgium; France

References

Tournilhac O, Bouabdallah K, Lecolant S, Hacini M, Laribi K, Bailly S, Belmondo T, Maerevoet MMF, Ysebaert L, Guidez S, Le Gouill S, Bonnet C, Andre M, Dupuis J, Thieblemont C, Bachy E, Daguindau N, Morschhauser F, Tricot S, Moulin C, Banos A, Houot R, Chauchet A, Gyan E, Cartron G, Farhat H, Camus V, Drenou B, Zerazhi H, Sibon D, Nicolas Virelizier E, Delette C, Snauwaert S, Bailly S, Delarue R, Carras S, Ledoux-Pilon A, Parrens M, Griolet S, Gaulard P, Delfau-Larue MH, de Leval LL, Damaj GL. Brentuximab Vedotin addition to Gemcitabine in Relapsed or Refractory Peripheral T-cell Lymphoma: a LYSA Phase II Study. Blood Adv. 2025 Aug 4:bloodadvances.2024015787. doi: 10.1182/bloodadvances.2024015787. Online ahead of print.

Reference Type: DERIVED

PMID: 40758949 (View on PubMed)

Related Links

https://www.lysarc.org/

Website of LYSARC

Other Identifiers

TOTAL

Identifier Type: -

Identifier Source: org_study_id