BREntuximab Vedotin in SEcond LIne Therapy BEfore Transplant

Hodgkin Lymphoma, Adult Clinical Trial

— BRESELIBET  

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 Details — Status: Recruiting

Administrative data

• NCT number: NCT04378647
• Other study ID #: GELTAMO18-HL
• Status: Recruiting
• Phase: Phase 2
• Start date: June 1, 2020
• Est. completion date: August 30, 2026

Study information

• Verified date: February 2024
• Source: Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea
• Contact: lucia palacios, MSc
• Phone: +18599134526
• Email: ensayosclinicos01[@]geltamo.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: August 30, 2026
• Est. primary completion date: August 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hodgkin Disease
• Hodgkin Lymphoma, Adult
• Lymphoma

Intervention

Drug:
• Induction with Brentuximab vedotin (BV)
3 cycles ESHAP plus antibody-drug conjugate brentuximab vedotin (BV) at a dose of 1.8 mg/kg IV
• Induction 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
• Consolidation 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)

Locations

Country	Name	City	State
Spain	Complexo Hospitalario Universitario A Coruña	A Coruña
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospital de La Santa Creu I Sant Pau	BArcelona
Spain	Institut Català D'Oncologia	Barcelona
Spain	Institut Català D'Oncologia - Hospital Duran I Reynals	Barcelona
Spain	Institut Català D'Oncologia - Hospital Germans Trias I Pujol	Barcelona	Barceolna
Spain	Hospital Universitario de Cruces	Bilbao
Spain	Hospital Universitario Virgen de Las Nieves	Granada
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital Ramón Y Cajal	Madrid
Spain	Hospital Universitario 12 de Octubre	MAdrid
Spain	Hospital Universitario Fundación Jiménez Díaz	Madrid
Spain	Hospital General Universitario J.M. Morales Meseguer	Murcia
Spain	Hospital Universitario Central de Asturias	Oviedo	Asturias
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital Universitario Marqués de Valdecilla	Santander	Cantabria
Spain	Hospital Universitario Virgen Del Rocío	Sevilla
Spain	Hospital Clínico Universitario de Valencia	Valencia
Spain	Hospital Universitario Y Politécnico La Fe	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Safety and tolerability	AEs, fertility,infections, and secondary malignancies	At the end of the 3 years of of last dose of consoldation Brentuximab VEdotin treatment
Primary	PET-CT result	PET-CT negative, Deauville scores 1 and 2	4-6 weeks after the Cycle 3 started (each cycle is 21 days)
Secondary	progression-free survival (PFS)	Evaluation of patient without progression of disease	At the end of two years of last dose of consoldation Brentuximab VEdotin treatment
Secondary	Duration of response	Lenght of time between date of evidence response and progression of disease or death	At the end of two years of last dose of consoldation Brentuximab VEdotin treatment
Secondary	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.	At the end of two years of last dose of consoldation Brentuximab VEdotin treatment
Secondary	Duration of response (DOR)	Time from first documentation of CR or PR to disease progression	At the end of two years of last dose of consoldation Brentuximab VEdotin treatment