Forschung

NIVAHL

NIVAHL - Nivolumab and AVD in early-stageun favorable classical Hodgkin lymphoma: A GHSG randomized, multicenter phase II trial

Objectives: The aim of the trial is to improve first-line treatment for early unfavorable cHL by introduction of the anti-PD-1 antibody Nivolumab with a truncated standard chemotherapy (AVD). Nivolumab is highly effective and well tolerated in rrHL. Limiting therapy-associated short- and long-term side effects of conventional therapies including impaired quality of life, secondary malignancies or organ damage is of utmost importance in the predominantly young HL patients. Nivolumab will be added to well established, but not most effective chemotherapy in two different regimens, while consolidating radiotherapy will be applied in both treatment groups. Synergistic effects of conventional agents with checkpoint inhibition may facilitate a highly effective therapy with limited toxicity. The primary objective is to show efficacy of the two experimental treatment strategies. Secondary objectives are to further evaluate efficacy, show safety and feasibility and perform correlative studies.

PRIMARY ENDPOINTS:
Complete remission (CR) rate at the end of treatment, assessed by central review

SECONDARY ENDPOINTS:

Key secondary endpoint: 

• Treatment-related morbidity (TRMorbidity)

Further secondary endpoints:

• 1- and 3-year progression-free survival (PFS)
• 1- and 3-year overall survival (OS)
• Quality of life including the prevalence of severe long-term fatigue
• Objective response rate (ORR; proportion of patients with complete or partial remission) at the end of Treatment
• Proportion of patients with negative PET/CT after four infusions of Nivolumab

Secondary exploratory endpoints:

• Correlative studies including biomarker analyses

ENTRY CRITERIA

• Histologically proven classical HL
• First diagnosis, no previous Treatment
• Age: 18-60 years
• Stage I, IIA with risk factors a-d, IIB with RF c-d:
  a) large mediastinal mass
  b) extranodal lesions
  c) elevated ESR
  d) ≥ 3 nodal areas
  confirmed by central review.

EXCLUSION CRITERIA

• Composite lymphoma or nodular lymphocytepredominant Hodgkin lymphoma (NLPHL)
• History of other malignancy ≤ 5 years
• Prior chemotherapy or radiation therapy
• Concurrent disease precluding protocol Treatment
• Pregnancy, lactation
• Non-compliance

TREATMENT GROUPS

Patients are randomized to one of the following two treatment groups and receive a total of 8x Nivolumab and 4 cycles AVD:

Treatment group A: 4x AVD with concomitant 8x Nivolumab (d1+d15 of each cycle)

Treatment group B: 4x Nivolumab, followed by 4x AVD with concomitant 4x Nivolumab (d1+d15 of cycle 1+2)

In both groups, 30 Gy involved-site radiotherapy (ISRT) will be applied after systemic therapy.

Zentrum im UCT Universitätsklinikum Frankfurt

Prüfer

Prüfer in der Hämatologie und Onkologie:
Dr. Teresa Halbsguth
Dr. Uta Brunnberg

Prüfer in der Strahlenklinik:
Prof. Dr. Emmanouil Fokas
Dr. med. Christian Keller

Studiensekretariat: 
Dr. Margarita Diaz Maguina

Universitätsklinikum Frankfurt/Main
Zentrum für Radiologie und Strahlentherapie
Theodor-Stern Kai 7
60590 Frankfurt am Main
Tel: +49 (0)69 6301-3742/4655
E-Mail: studien-strahlen@unimedizin-ffm.de

Ansprechpartner Leiter der klinischen Prüfung

Prof. Dr. med. Andreas Engert
Uniklinikum Köln
Klinik I für Innere Medizin
Kerpener Str. 62
50937 Köln

FINANCIAL SUPPORT: The trial is financially supported and Nivolumab is supplied free of charge by Bristol-Myers Squibb