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RecruitingNCT04378647BRESELIBETUpdated Feb 26, 2024

BREntuximab Vedotin in SEcond LIne Therapy BEfore Transplant

A Phase 2 interventional study of Induction with Brentuximab vedotin (BV) and Induction without Brentuximab Vedotin in Hodgkin Lymphoma, Adult, sponsored by Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea. Recruiting at 19 sites in Spain. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2024-02-26.

Sponsored by Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
150
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study summary

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

Read the 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.

02

Conditions studied

  • Hodgkin Lymphoma, Adult
03

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
150 participants (estimated)

Study arms

  • Active comparator
    Induction ESHAP

    3 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 \[25 mg/m2/day IV, D1-4\]

    Drug: Induction without Brentuximab Vedotin · Drug: Consolidation with Brentuximab Vedotin

  • Experimental
    Induction BV-ESHAP

    3 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 \[1.8 mg/kg IV, D1\]

    Drug: Induction with Brentuximab vedotin (BV) · Drug: Consolidation with Brentuximab Vedotin

Interventions

  • DrugInduction with Brentuximab vedotin (BV)

    3 cycles ESHAP plus antibody-drug conjugate brentuximab vedotin (BV) at a dose of 1.8 mg/kg IV

    Also known as: Adcetris treatment + ESHAP as salvage therapy

  • DrugInduction without Brentuximab Vedotin

    3 cycles of ESHAP as a standard of care therapy for those patients with primary refractory cHL and those patients relapsing after first-line therapy

    Also known as: ESHAP treatment as salvage therapy

  • DrugConsolidation with Brentuximab Vedotin

    Up to 13 or 16 cycles of antibody-drug conjugate brentuximab vedotin (BV) at doses of 1.8 mg/kg iv every 21 days)

    Also known as: Adcetris treatment as consolidation

05

What researchers measure

Primary outcomes

  1. PET-CT result

    PET-CT negative, Deauville scores 1 and 2

    Time frame: 4-6 weeks after the Cycle 3 started (each cycle is 21 days)

Secondary outcomes

  1. progression-free survival (PFS)

    Evaluation of patient without progression of disease

    Time frame: At the end of two years of last dose of consoldation Brentuximab VEdotin treatment

  2. Duration of response

    Lenght of time between date of evidence response and progression of disease or death

    Time frame: At the end of two years of last dose of consoldation Brentuximab VEdotin treatment

  3. Overall Survival (OS)

    Time from entry onto the clinical trial (random assignment in a phase III study) until death as a result of any cause.

    Time frame: At the end of two years of last dose of consoldation Brentuximab VEdotin treatment

  4. Duration of response (DOR)

    Time from first documentation of CR or PR to disease progression

    Time frame: At the end of two years of last dose of consoldation Brentuximab VEdotin treatment

Other outcomes

  1. Safety and tolerability

    AEs, fertility,infections, and secondary malignancies

    Time frame: At the end of the 3 years of of last dose of consoldation Brentuximab VEdotin treatment

06

Study locations

19 of 19 sites recruiting
  • Hospital Universitario Central de Asturias
    Oviedo, Asturias 33011, Spain
    Recruiting
  • Institut Català D'Oncologia - Hospital Germans Trias I Pujol
    Barcelona, Barceolna 08916, Spain
    Recruiting
  • Hospital Universitario Marqués de Valdecilla
    Santander, Cantabria 39008, Spain
    Recruiting
  • Complexo Hospitalario Universitario A Coruña
    A Coruña, 15006, Spain
    Recruiting
  • Hospital Clínic de Barcelona
    Barcelona, 08036, Spain
    Recruiting
  • Hospital de La Santa Creu I Sant Pau
    BArcelona, 08041, Spain
    Recruiting
  • Institut Català D'Oncologia - Hospital Duran I Reynals
    Barcelona, 08908, Spain
    Recruiting
  • Institut Català D'Oncologia
    Barcelona, 08908, Spain
    Recruiting
  • Hospital Universitario de Cruces
    Bilbao, 48903, Spain
    Recruiting
  • Hospital Universitario Virgen de Las Nieves
    Granada, 18014, Spain
    Recruiting
  • Hospital General Universitario Gregorio Marañón
    Madrid, 28007, Spain
    Recruiting
  • Hospital Ramón Y Cajal
    Madrid, 28034, Spain
    Recruiting
  • Hospital Universitario Fundación Jiménez Díaz
    Madrid, 28040, Spain
    Recruiting
  • Hospital Universitario 12 de Octubre
    MAdrid, 28041, Spain
    Recruiting
  • Hospital General Universitario J.M. Morales Meseguer
    Murcia, 30008, Spain
    Recruiting
  • Hospital Universitario de Salamanca
    Salamanca, 37007, Spain
    Recruiting
  • Hospital Universitario Virgen Del Rocío
    Sevilla, 41013, Spain
    Recruiting
  • Hospital Universitario Y Politécnico La Fe
    Valencia, 46026, Spain
    Recruiting
  • Hospital Clínico Universitario de Valencia
    Valencia, Spain
    Recruiting
07

Registry details

Key details

Study ID
NCT04378647
Lead sponsor
Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea
Responsible party
Sponsor
First posted
May 7, 2020
Start date
Jun 1, 2020
Primary completion
Aug 30, 2026 (estimated)
Completion
Aug 30, 2026 (estimated)
Last update
Feb 26, 2024

Study contacts

lucia palacios, MSc
Contact
ensayosclinicos01@geltamo.com
+18599134526
Angel Cedillo, MSc
Contact
sc@geltamo.com
+34 91315780
Anna Sureda, PhD
principal investigator · Institut Català d'Oncologia, Hospital Duran i Reynals

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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