Clinical Trials /

BREntuximab Vedotin in SEcond LIne Therapy BEfore Transplant

NCT04378647

Description:

A Randomized Phase IIb Study, Evaluating Efficacy of Salvage Therapy with Brentuximab Vedotin-ESHAP vs ESHAP in Patients with Relapsed / Refractory Classical Hodgkin's Lymphoma, Followed by Brentuximab Vedotin Consolidation (instead of Autologous Hematopoietic Stem Cell Transplantation) in Those who Attained a Metabolic Complete Remission after Salvage Therapy

Related Conditions:
  • Classical Hodgkin Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: BREntuximab Vedotin in SEcond LIne Therapy BEfore Transplant
  • Official Title: A Randomized Phase IIb Study, Evaluating Efficacy of Salvage Therapy With Brentuximab Vedotin-ESHAP vs ESHAP in Patients With Relapsed / Refractory Classical Hodgkin's Lymphoma, Followed by Brentuximab Vedotin Consolidation (Instead of Autologous Hematopoietic Stem Cell Transplantation) in Those Who Attained a Metabolic Complete Remission After Salvage Therapy

Clinical Trial IDs

  • ORG STUDY ID: GELTAMO18-HL
  • NCT ID: NCT04378647

Conditions

  • Hodgkin Lymphoma, Adult

Interventions

DrugSynonymsArms
Induction with Brentuximab vedotin (BV)Adcetris treatment + ESHAP as salvage therapyInduction BV-ESHAP
Induction without Brentuximab VedotinESHAP treatment as salvage therapyInduction ESHAP
Consolidation with Brentuximab VedotinAdcetris treatment as consolidationInduction BV-ESHAP

Purpose

A Randomized Phase IIb Study, Evaluating Efficacy of Salvage Therapy with Brentuximab Vedotin-ESHAP vs ESHAP in Patients with Relapsed / Refractory Classical Hodgkin's Lymphoma, Followed by Brentuximab Vedotin Consolidation (instead of Autologous Hematopoietic Stem Cell Transplantation) in Those who Attained a Metabolic Complete Remission after Salvage Therapy

Detailed Description

      A phase IIb open label multi-center trial in patients with refractory / relapsed cHL.

      Patients are randomized (1:1) to receive:

      • ESHAP- BV (Etoposide [40 mg/m2/ day IV, D1-4], Solumedrol [250 mg/day IV, D1-4], high dose
      Ara-C [2 g/m2 IV, D5] and cisplatinum [25 mg/m2/day IV, D1-4] + BV [1.8 mg/kg IV, D1], every
      21 days (3 cycles, q21 days).

      Or

      • ESHAP (Etoposide [40 mg/m2/ day IV, D1-4], Solumedrol [250 mg/day IV, D1-4], high dose
      Ara-C [2 g/m2 IV, D5] and cisplatinum [25 mg/m2/day IV, D1-4] (3 cycles, q21 days)

      Stem cell collection will be performed in all patients according to institutional guidelines,
      but preferably after the first / second cycle of ESHAP-BV or ESHAP.

      Patients attaining a mCR (Deauville 1, 2) after receiving 3 cycles of ESHAP-BV, will receive
      up to 13 cycles of BV consolidation (administered every 3 weeks, over 39 weeks).

      Patients who were randomized to ESHAP and attained a mCR after receiving 3 cycles will
      receive up to 16 cycles of BV (same dosage and time intervals).

      Patients who attained less than mCR following ESHAP-BV/ESHAP they will be taken out of the
      trial and will be treated according to their physician's clinical decision. However, they
      will be followed in order to evaluate their clinical outcome in terms of ORR, CR rate, TTNT2
      and OS, that will be analyzed the study separately.
    

Trial Arms

NameTypeDescriptionInterventions
Induction ESHAPActive Comparator3 Cycles ESHAP ( 21 days) : Etoposide [40 mg/m2/ day IV, D1-4], Solumedrol [250 mg/day IV, D1-4], High dose Ara-C [2 g/m2 IV, D5] Cisplatinum [25 mg/m2/day IV, D1-4]
  • Induction without Brentuximab Vedotin
  • Consolidation with Brentuximab Vedotin
Induction BV-ESHAPExperimental3 Cycles of Brentuximab VEedotin + ESHAP ( 21 days) : Etoposide [40 mg/m2/ day IV, D1-4], Solumedrol [250 mg/day IV, D1-4], High dose Ara-C [2 g/m2 IV, D5] Cisplatinum [25 mg/m2/day IV, D1-4] Brentuximab Vedotin [1.8 mg/kg IV, D1]
  • Induction with Brentuximab vedotin (BV)
  • Consolidation with Brentuximab Vedotin

Eligibility Criteria

        Inclusion Criteria:

        Patients with classical HL CD30+ confirmed histologically (either at the time of diagnosis
        / at the time of first relapse) will be included in the trial

          -  Male or female patients 18 to 65 years of age

          -  Voluntary written informed consent must be given before performance of any
             study-related procedure not part of standard medical care, with the understanding that
             consent may be withdrawn by the patient at any time without prejudice to future
             medical care

          -  Female patient is either post-menopausal for at least 1 year before the screening
             visit or surgically sterile or if of childbearing potential, agree to practice 2
             effective methods of contraception, at the same time, from the time of signing the
             informed consent through 6 months after the last dose of study drug, or agrees to
             completely abstain from heterosexual intercourse

          -  Male patients, even if surgically sterilized, (i.e., status post-vasectomy) agree to
             practice effective barrier contraception during the entire study period and through 6
             months after the last dose of study drug, or agrees to completely abstain from
             heterosexual intercourse

          -  ECOG 0 to 2

          -  Measurable disease at time of enrolment (lymphadenopathy/ extranodal mass of at least
             1.5 cm)

          -  No evidence of neuropathy grade ≥2

          -  Clinical laboratory values as specified in the protocol below within 7 days before the
             first dose of study drug

        Exclusion Criteria:

          -  Lymphocyte predominant nodular Hodgkin's lymphoma

          -  Prior treatment with brentuximab vedotin

          -  Female patient who are both lactating and breast-feeding or have a positive serum
             pregnancy test during the screening period or a positive pregnancy test on Day 1
             before first dose of study drug

          -  Any serious medical or psychiatric illness that could, in the investigator's opinion,
             potentially interfere with the completion of treatment according to the protocol.

          -  Known cerebral or meningeal disease (HL or any other etiology), including signs or
             symptoms of progressive multifocal leukoencephalopathy (PML)

          -  Symptomatic neurologic disease compromising normal activities of daily living or
             requiring medic

          -  Any sensory or motor peripheral neuropathy greater than or equal to Grade 2

          -  Known history of any of the following cardiovascular conditions defined in the
             protocol

          -  Any active systemic viral, bacterial, or fungal infection requiring systemic
             antibiotics within 2 weeks prior to first study drug dose

          -  Patients that have not completed any prior treatment chemotherapy and/or other
             investigational agents within at least 5 half-lives (or 28 days if the half-lives are
             unknown) of last dose of that prior treatment

          -  Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient
             contained in the drug formulation of brentuximab vedotin.

          -  Known human immunodeficiency virus (HIV) positive

          -  Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C
             infection

          -  Focal radiation therapy within 30 days prior to study recruitment

          -  Major surgery within 28 days prior to randomization

          -  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:65 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:PET-CT result
Time Frame:4-6 weeks after the Cycle 3 started (each cycle is 21 days)
Safety Issue:
Description:PET-CT negative, Deauville scores 1 and 2

Secondary Outcome Measures

Measure:progression-free survival (PFS)
Time Frame:At the end of two years of last dose of consoldation Brentuximab VEdotin treatment
Safety Issue:
Description:Evaluation of patient without progression of disease
Measure:Duration of response
Time Frame:At the end of two years of last dose of consoldation Brentuximab VEdotin treatment
Safety Issue:
Description:Lenght of time between date of evidence response and progression of disease or death
Measure:Overall Survival (OS)
Time Frame:At the end of two years of last dose of consoldation Brentuximab VEdotin treatment
Safety Issue:
Description:Time from entry onto the clinical trial (random assignment in a phase III study) until death as a result of any cause.
Measure:Duration of response (DOR)
Time Frame:At the end of two years of last dose of consoldation Brentuximab VEdotin treatment
Safety Issue:
Description:Time from first documentation of CR or PR to disease progression

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea

Last Updated

May 7, 2020