Hodgkin Lymphom

HD 21
BRESELIBET

HD 21

HD21 for advanced stages: Treatment optimization trial in the first-line treatment of advanced stage Hodgkin lymphoma; comparison of 4-6 cycles of escalated BEACOPP with 4-6 cycles of BrECADD

Synopsis

Short title: HD 21

Title: HD21 for advanced stages: Treatment optimization trial in the first-line treatment of advanced stage Hodgkin lymphoma; comparison of 4-6 cycles of escalated BEACOPP with 4-6 cycles of BrECADD

Status: active, not recruiting

Start: April 2017 (in Austria)

Coordinating Investigator: Univ. Prof. Dr. Richard Greil

EudraCT Number: 2014-005130-55

ClinicalTrialsID: NCT02661503

Number of patients: 1585 (international), 93 (national)

Sponsor: GHSG (German Hodgkin Studygroup), AGMT Sponsor representative in Austria

Design

In this prospective, multicenter, randomized and open-label trial, patients in the standard group are treated with either 4 or 6 cycles of escalated BEACOPP according to the results of the interim staging (PET-2 negative patients receive 4 cycles of escalated BEACOPP, PET-2 positive patients receive 6 cycles of escalated BEACOPP) . Patients in the experimental group receive either 4 or 6 cycles of the BrECADD chemotherapy regimen, again according to the results of the interim staging (PET-2 negative patients receive 4 cycles of BrECADD, PET-2 positive patients receive 6 cycles of BrECADD).

In both groups, patients with PET positive residual tumor masses at the end of chemotherapy according to PET-4 or PET-6 are subjected to local irradiation with 30 Gy.

Patients without signs of active tumor at restaging after chemotherapy do not receive any further treatment and directly enter the follow-up program.

Assessments from the interim staging and the restaging after chemotherapy (without regard to the number of administered treatment cycles) are reviewed in Cologne.

Elderly cohort (61 – 75 years) was added and will be treated without randomisation in the BrECADD arm.

Primary endpoints:
  • Progression free survival and treatment related morbidity (TRMB)
Secondary endpoints:
  • CR rate after completion of chemotherapy
  • Overall survival
  • Infertility rate at 1 yera (determined by hormone levels)
  • Second malignancies
  • Number of serious adverse events within 30 days after end of treatment
  • Therapy adherence
  • Quality of life before, during and after therapy

Inclusion / Exclusion criteria

Inclusion criteria (selected):
  • Histologically proven classical Hodgkin lymphoma
  • Patient has had no previous treatment for HL
  • Age at entry: 18 – 60 years (61 – 75 years for elderly cohort)
  • CS (PS) IIB with large mediastinal mass, extra nodal disease or CS (PS) III; IV
  • Normal organ function (except for HL-related functional disorders)
  • Estimated life expectancy > 3 months
  • In women: negative pregnancy test
Exclusion criteria (selected):
  • Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) or composite lymphoma
  • Malignant disease within the last 5 years (Exceptions: basalioma, carcinoma in situ e.g. of the cervix uteri, completely resected melanoma TNMpT1)
  • Chemotherapy or radiotherapy in medical history
  • ECOG >2
  • Long-term administration (> 6 months) of corticosteroids or antineoplastic drugs
  • Peripheral neuropathy > CTCAE grade 1
  • Unsafe contraception

BRESELIBET

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

Synopsis

Short title: BRESELIBET (BREntuximab Vedotin in SEcond LIne Therapy BEfore Transplant)

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

Status: active, not recruiting

Start: Mai 2021 (in Austria)

Coordinating Investigator: Univ. Prof. Dr. Richard Greil

EudraCT Number: 2019-002746-21

ClinicalTrialsID: NCT04378647

Number of patients: 150 (international), 4 (national)

Sponsor: GELTAMO (Grupo Español de Linfomas y Trasplante Autólogo de Médula Ósea), AGMT Sponsor representative in Austria

Design

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], Methylprednisolone [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], Methylprednisolone [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.

Primary endpoints:
  • The comparison of the metabolic complete remission (mCR) of ESHAP-brentuximab vedotin (BV) vs ESHAP as salvage strategies in patients with relapsed / refractory classical Hodgkin’s Lymphoma (cHL) after the 3 first cycles assessed by PET-TC. The Deauville criteria will be used being negative, Deauville scores 1 and 2.
Secondary endpoints (selected):
  • Relapse
  • Response criteria
  • Duration of response (DOR)
  • Progression-free survival (PFS)
  • Overall survival (OS)
  • Time to Progression (TTP)
  • Time to Next Treatment (TTNT)
  • Safety and tolerability

Inclusion / Exclusion criteria

Inclusion criteria (selected):
  • Relapsed/refractory cHL confirmed histologically (either at the time of diagnosis / at the time of first relapse)
  • Male or female patients 18 to 65 years of age
  • 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
Exclusion criteria (selected):
  • Nodular lymphocyte-predominant HL
  • Prior treatment with brentuximab vedotin
  • Known cerebral or meningeal disease (HL or any other etiology), including signs or symptoms of progressive multifocal leukoencephalopathy (PML)
  • 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 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

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