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

Sponsor
The Lymphoma Academic Research Organisation (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT03496779
Collaborator
(none)
71
Enrollment
39
Locations
1
Arm
53.7
Anticipated Duration (Months)
1.8
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease Intervention/Treatment Phase
  • Drug: Brentuximab Vedotin - induction
  • Drug: Gemcitabine
  • Drug: Brentuximab Vedotin - maintenance
  • Procedure: autologous or allogeneic stem cell transplantation
 Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
71 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Intervention Model Description:
This study is an open label, multicenter phase 2 study. Patients treated with gemcitabine will receive brentuximab vedotin (GBv) for 4 cycles of induction.This study is an open label, multicenter phase 2 study. Patients treated with gemcitabine will receive brentuximab vedotin (GBv) for 4 cycles of induction.
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Study of Brentuximab Vedotin in Patients With Relapsed or Refractory Peripheral T-cell Lymphoma Treated With Gemcitabine Followed by Brentuximab Vedotin Maintenance
Actual Study Start Date :
Apr 10, 2018
Actual Primary Completion Date :
Jan 31, 2020
Anticipated Study Completion Date :
Oct 1, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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.

Drug: Brentuximab Vedotin - induction
Brentuximab vedotin 1.8 mg/kg at D8 of a 28-day cycle - 4 cycles = 16 weeks for combined chemotherapy
Other Names:
  • Adcetris

    • Drug: Gemcitabine
    Gemcitabine 1000 mg/m² at D1 and D15 of a 28-day cycle - 4 cycles = 16 weeks for combined chemotherapy
    Other Names:
  • Gemzar

    • 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
    Other Names:
  • Adcetris

    • Procedure: 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

    Outcome Measures

    Primary Outcome Measures

    1. Overall Response Rate (ORR) [16 weeks = 4 cycles or permanent treatment discontinuation]

      rate of patient in Complete/Partial response according to the international response criteria for malignant lymphoma (Lugano Classification 2014 - CT-Based Response).

    Secondary Outcome Measures

    1. Progression-Free Survival (PFS) [16 weeks = 4 cycles or permanent treatment discontinuation]

      % of patient who did not progressed according to the international response criteria for malignant lymphoma (Lugano Classification 2014 - CT-Based Response).

    2. Progression-Free Survival (PFS) [4.5 years]

      % of patient who did not progressed according to the international response criteria for malignant lymphoma (Lugano Classification 2014 - CT-Based Response).

    3. Complete Response Rate (CRR) [16 weeks = 4 cycles or permanent treatment discontinuation]

      rate of patient in Complete Response (CR)according to the international response criteria for malignant lymphoma (Lugano Classification 2014 - CT-Based Response).

    4. Duration of Response (DoR) [16 weeks = 4 cycles or permanent treatment discontinuation]

      duration between the Complete/Partial Response and the Progression according to the international response criteria for malignant lymphoma (Lugano Classification 2014 - CT-Based Response) = duration between the Complete/Partial Response and the Progression

    5. Duration of Response (DoR) [4.5 years]

      duration between the Complete/Partial Response and the Progression according to the international response criteria for malignant lymphoma (Lugano Classification 2014 - CT-Based Response) = duration between the Complete/Partial Response and the Progression

    6. Time to Treatment Failure (TTF) [16 weeks = 4 cycles or permanent treatment discontinuation]

      duration between the inclusion and the premature end of treatment

    7. Time to next treatment [16 weeks = 4 cycles or permanent treatment discontinuation]

      Duration between the end of the studied treatment and the beginning of a new one after progression

    8. Overall Survival (OS) [16 weeks = 4 cycles or permanent treatment discontinuation]

      % of patient still alive

    9. Overall Survival (OS) [4.5 years]

      % of patient still alive

    10. Overall response rate [4.5 years]

      rate of patient in Complete/Partial response according to the international response criteria for malignant lymphoma (Lugano Classification 2014 - CT-Based Response).

    11. Number of Serious Adverse Events (SAE) during the induction period [16 weeks = 4 cycles or permanent treatment discontinuation]

    12. Number of Serious Adverse Events (SAE) during the maintenance period [36 weeks = 12 cycles or permanent treatment discontinuation]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 ZNA Stuivenberg Antwerpen Belgium 2060
    2 A. Z. Sint-Jan Bruges Belgium 8000
    3 Clinique Universitaire Saint LUC Brussels Belgium 1200
    4 Institut Jules Bordet Brussels Belgium
    5 ULB Hôpital Erasme Brussels Belgium
    6 UZ Gent Gent Belgium 9000
    7 CHU de Liege Liege Belgium 4000
    8 CHU UCL Namur Yvoir Belgium
    9 IHBN - CHU Cote de Nacre Amiens France 80054
    10 CHU d'Amiens Amiens France
    11 CHU Angers Angers France 49033
    12 CH d'Avignon - Hôpital Henri Dufaut Avignon France 84000
    13 CH Côte Basque Bayonne France 64100
    14 CHU de Besançon - Hôpital Jean Minjoz Besançon France 25030
    15 CH Chambéry Chambery France 73011
    16 CHU d'Estaing Clermont-Ferrand France 63000
    17 APHP - Hopital Henri Mondor Creteil France 94010
    18 CHU de Dijon - Hôpital le Bocage Dijon France 21000
    19 CHU Grenoble Grenoble France 38043
    20 CH de Versailles - Hopital André Mignot Le Chesnay France 78157
    21 CH du Mans Le Mans France 72000
    22 CHRU de Lille - Hôpital Claude Huriez Lille France
    23 CHU de Limoges Limoges France
    24 Centre Leon Berard Lyon Cedex 8 France 69373
    25 Centre Hospitalier Annecy Genevois Metz-Tessy France 74374
    26 CH Saint-Eloi Montpellier France 34295
    27 CH de Mulhouse Sud Alsace Mulhouse France 68070
    28 CHU Nancy - Brabois Nancy France 54511
    29 CHU de Nantes - Hôtel Dieu Nantes France 44093
    30 APHP - Hôpital Saint Louis Paris Cedex 10 France 75475
    31 APHP - Hôpital Necker Paris France 75015
    32 Centre François Magendie - Hôpital du Haut Lévêque Pessac France 33604
    33 Centre Hospitalier Lyon Sud Pierre Bénite France 69495
    34 CHU de Poitiers - Hôpital de la Milétrie Poitiers France 86021
    35 CHU De Rennes Rennes France 35033
    36 Centre Henri BECQUEREL Rouen France 76038
    37 CHU de Toulouse Toulouse France 31059
    38 CHRU de Tours Tours France 37044
    39 CH de Valenciennes Valenciennes France 59322

    Sponsors and Collaborators

    • The Lymphoma Academic Research Organisation

    Investigators

    • Study Chair: Richard DELARUE, MD, APHP - Hôpital Necker
    • Study Chair: Olivier TOURNILHAC, MD, CHU Estaing - Clermont Ferrant

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    The Lymphoma Academic Research Organisation
    ClinicalTrials.gov Identifier:
    NCT03496779
    Other Study ID Numbers:
    • TOTAL
    First Posted:
    Apr 12, 2018
    Last Update Posted:
    Sep 16, 2021
    Last Verified:
    Sep 1, 2021
    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
    Brentuximab Vedotin
    T-cell lymphoma
    Additional relevant MeSH terms:
    Lymphoma
    Lymphoma, T-Cell
    Lymphoma, T-Cell, Peripheral
    Gemcitabine
    Brentuximab Vedotin
    Antibodies, Monoclonal

    Study Results

    No Results Posted as of Sep 16, 2021