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
Hodgkin Lymphom
- HD 21
- AERN
HD 21
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: open (only for elderly cohort), randomised main study is 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), 90 (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
AERN
AERN – Abscopal Effect of Radiotherapy and Nivolumab in anti-PD1 Pretreated Relapsed or Refractory classical Hodgkin Lymphoma – An international multicenter Phase II trial
Synopsis
Short title: AERN
Title: AERN – Abscopal Effect of Radiotherapy and Nivolumab in anti-PD1 Pretreated Relapsed or Refractory classical Hodgkin Lymphoma – An international multicenter Phase II trial
Status: planned
Start: Dezember 2020 (in Austria)
Coordinating Investigator: Univ. Prof. Dr. Richard Greil
EudraCT Number: 2017-003334-82
ClinicalTrialsID: NCT03480334
Number of patients: 29 (international), 4 (national)
Sponsor: GHSG (German Hodgkin Studygroup), AGMT Sponsor representative in Austria
Design
The aim of the trial is to improve efficacy of nivolumab in patients with relapsed or refractory HL who recently progressed on anti-PD1 therapy. Nivolumab is highly effective and well tolerated in rrHL, nevertheless CR-rates are low and a considerable proportion of patients suffers from progressive disease. Localized RT induces an immunogenic effect which might work synergistically and facilitate augmented systemic (i.e. abscopal) responses in combination with nivolumab.
The primary objective of the trial is to show efficacy of the experimental treatment strategy. Secondary objectives are to further evaluate efficacy, show safety and feasibility and perform correlative studies.
Primary endpoints:
- Abscopal response rate (ARR-6) with abscopal response centrally confirmed as restaging result after RT to a single lesion and at least four but not more than six nivolumab infusions (RE-6 result)
Secondary endpoints:
- Overall abscopal response rate (OARR)
- Overall response rate (ORR)
- Duration of response (DOR)
- Progression-free survival (PFS)
- Overall survival (OS)
- Adverse events (AE)
- Feasibility aspects
- Quality of life (Qol) and life situation (LS) aspects
- Correlative studies
Inclusion / Exclusion criteria
Inclusion criteria (selected):
- Relapsed/refractory cHL with progression while treated with an anti-PD1 antibody or
- Relapsed/refractory cHL with stable disease for > 6 months as best response to ongoing anti-PD1 antibody therapy
- At least two distinct FDG-avid Hl-lesions with at least 5cm distance between them, and one of them considered eligible for irradiation with 20Gy
- Age >18 years, all sexes
Exclusion criteria (selected):
- Nodular lymphocyte-predominant HL or grey-zone lymphoma
- Evidence of active, non-infectious lung disorder with DLCOc <50%
- History of longterm or ongoing ingestion of immunosuppressive agents >10 mg prednisone
- Any other serious disease or organ dysfunction which might impair protocol treatment