Clinical Trials /

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

NCT03496779

Description:

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).

Related Conditions:
  • Peripheral T-Cell Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Brentuximab Vedotin in Patients With R/R PTCL Treated With Gemcitabine
  • 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

Clinical Trial IDs

  • ORG STUDY ID: TOTAL
  • NCT ID: NCT03496779

Conditions

  • Refractory Peripheral T-Cell Lymphoma
  • Relapsed Peripheral T-Cell Lymphoma

Interventions

DrugSynonymsArms
Brentuximab Vedotin - inductionAdcetrisExperimental
GemcitabineGemzarExperimental
Brentuximab Vedotin - maintenanceAdcetrisExperimental

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
ExperimentalExperimentalPatients 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.
  • Brentuximab Vedotin - induction
  • Gemcitabine
  • Brentuximab Vedotin - maintenance

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.
      
Maximum Eligible Age:80 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate (ORR)
Time Frame:16 weeks = 4 cycles or permanent treatment discontinuation
Safety Issue:
Description: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

Measure:Progression-Free Survival (PFS)
Time Frame:16 weeks = 4 cycles or permanent treatment discontinuation
Safety Issue:
Description:% of patient who did not progressed according to the international response criteria for malignant lymphoma (Lugano Classification 2014 - CT-Based Response).
Measure:Progression-Free Survival (PFS)
Time Frame:4.5 years
Safety Issue:
Description:% of patient who did not progressed according to the international response criteria for malignant lymphoma (Lugano Classification 2014 - CT-Based Response).
Measure:Complete Response Rate (CRR)
Time Frame:16 weeks = 4 cycles or permanent treatment discontinuation
Safety Issue:
Description:rate of patient in Complete Response (CR)according to the international response criteria for malignant lymphoma (Lugano Classification 2014 - CT-Based Response).
Measure:Duration of Response (DoR)
Time Frame:16 weeks = 4 cycles or permanent treatment discontinuation
Safety Issue:
Description: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
Measure:Duration of Response (DoR)
Time Frame:4.5 years
Safety Issue:
Description: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
Measure:Time to Treatment Failure (TTF)
Time Frame:16 weeks = 4 cycles or permanent treatment discontinuation
Safety Issue:
Description:duration between the inclusion and the premature end of treatment
Measure:Time to next treatment
Time Frame:16 weeks = 4 cycles or permanent treatment discontinuation
Safety Issue:
Description:Duration between the end of the studied treatment and the beginning of a new one after progression
Measure:Overall Survival (OS)
Time Frame:16 weeks = 4 cycles or permanent treatment discontinuation
Safety Issue:
Description:% of patient still alive
Measure:Overall Survival (OS)
Time Frame:4.5 years
Safety Issue:
Description:% of patient still alive
Measure:Overall response rate
Time Frame:4.5 years
Safety Issue:
Description:rate of patient in Complete/Partial response according to the international response criteria for malignant lymphoma (Lugano Classification 2014 - CT-Based Response).
Measure:Number of Serious Adverse Events (SAE) during the induction period
Time Frame:16 weeks = 4 cycles or permanent treatment discontinuation
Safety Issue:
Description:
Measure:Number of Serious Adverse Events (SAE) during the maintenance period
Time Frame:36 weeks = 12 cycles or permanent treatment discontinuation
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:The Lymphoma Academic Research Organisation

Trial Keywords

  • Brentuximab Vedotin
  • T-cell lymphoma

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