Clinical trial NCT04866654: Radiation Free Chemotherapy for Early Hodgkin Lymphoma
Official title: Radiation-Free Therapy for the Initial Treatment of Good Prognosis Early Non-bulky HL, Defined by a Low Metabolic Tumor Volume and a Negative Interim PET After 2 Chemotherapy Cycles- RAFTING
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Hodgkin Lymphoma
Lead sponsor: Medical University of Gdansk
Sponsor class: OTHER
First posted: 2021-04-30
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The results of the present study will provide information on short-term safety and efficacy of a iPET and MTV-adapted therapeutic strategy, aimed to assess the feasibility and safety on immediate disease control of a standard ABVD chemotherapy without any further treatment in patients with a very low risk or treatment failure. A second very important endpoint will be the efficacy of INRT "on demand" followed by Nivolumab maintenance for one year to rescue patients failing first-line treatment and relapsing with the pattern of "limited relapse" in terms of 3-Y failure from 2 relapse (FF2R). Patients entering into the study will be also asked to participate to a long-term follow up study (beyond ten years) to assess the prevalence of late-onset cardiovascular effects and secondary tumors in the cohort of patients enrolled in the experimental and control arm of the study. An exploratory endpoint has been also added such as the role of Minimal Residual Disease (MRD) detection by cell-free DNA assay on peripheral blood samples obtained during treatment in predicting long-term disease control.


Eligibility criteria: Inclusion Criteria:

* Male or female patients aged 18-60.
* Treatment-naïve, HL patients with Ann Arbor stage I or II A non-bulky disease stratified according to modified EORTC Criteria (refer to Appendix A);
* Patients must have histologically confirmed classical HL according to the current World Health Organization Classification (nodular sclerosis, mixed cellularity, lymphocytes rich, lymphocytes depleted, or classical HL NOS \[not otherwise specified\];
* ECOG performance status 0-2
* Hemoglobin must be \> 8 gr./dL
* Absolute neutrophil count ≥ 1,000/μL
* Platelet count ≥ 100,000/μL
* Voluntary written consent to take part to the study
* Serum Creatinine \< 2.0 mg/dL and/or Creatinine clearance or calculated Creatinine clearance \> 40 mL/minute
* Total bilirubin must be \< 2.0 x the upper limit of normal (ULN) unless known Gilbert syndrome
* ALT or AST must be \< 3 x the upper limit of normal.
* Female patients: if postmenopausal for at least 1 year before enrolment or, if fertile - agreeing to practice 2 effective methods of contraception or agreeing to practice true abstinence.
* Male patients should agree to practice barrier contraception or to practice abstinence

Exclusion Criteria:

* Composite lymphoma or nodular lymphocyte-predominant Hodgkin lymphoma;
* Bulky disease (Lugano 2014 definition: single or conglomerated nodal mass with the largest diameter measuring 10 or more centimeters);
* B symptoms;
* Extra nodal site involved by disease;
* Female patients who are both lactating and breastfeeding or who have a positive serum pregnancy test during the screening period or a positive pregnancy test on Day 1 before first dose of study drug;
* Uncompensated diabetes mellitus requiring insulin therapy;
* Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol;
* Known human immunodeficiency virus (HIV) infection with a positive search for HIV antigens by immunoblot and/or circulating copies of HIV-RNA;
* Active hepatitis B with circulating copies of HBV-DNA, or active hepatitis C infection with circulating copies of HCV-RNA;
* Severely impaired, lung and renal function;
* Diagnosed or treated for another malignancy within 3 years before the first dose or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection;
* Active autoimmune disorder in treatment with immunosuppressive drugs
* A left-ventricular ejection fraction \< 50%;
* Myocardial infarction within 2 years of study entry.
* Pregnancy or lactation.

Primary outcomes:
measure: Efficacy exploration in terms of 3-Y PFS of chemotherapy alone
timeFrame: During follow-up (36 months) after the end of treatment
Secondary outcomes:
measure: Efficacy exploration in terms of 3-Y PFS of chemotherapy plus Nivolumab
timeFrame: During follow-up (36 months) after the end of treatment
measure: Efficacy exploration in terms of 3-Y freedom from 2nd treatment failure (3-Y FF2TF) of chemotherapy followed by radiotherapy "on demand" plus Nivolumab maintenance
timeFrame: During follow-up (36 months) after the end of treatment
measure: Safety exploration in terms of 3-Y OS of a treatment with chemotherapy alone
timeFrame: During follow-up (36 months) after the end of treatment
measure: Evaluation the ability of cell-free DNA (cfDNA) assay
timeFrame: During follow-up (36 months) after the end of treatment
Other outcomes:
Locations:
city: Pavia
country: Italy
facility: Hematology Department IRCCS Policlinico San Matteo
state: P.le Golgi 19
city: Bergamo
country: Italy
facility: Ospedale Papa Giovanni XXIII
state: Piazza OMS, 1
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
state: Via Giuseppe Ripamonti 435
city: Cuneo
country: Italy
facility: Hematology Department Azienda Ospedaliera S. Croce e Carle
state: Via Michele Coppino, 26
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Federico II
state: Via S.Pansini, 5
city: Bari
country: Italy
facility: IRCCS Istituto Tumori Giovanni Paolo II
state: Viale Orazio Flacco, 65
city: Roma
country: Italy
facility: Policlinico Università Tor Vergata
state: Viale Oxford, 81
city: Ancona
country: Italy
facility: Azienda Ospedaliero - Universitaria Ospedali Riuniti
city: Cagliari
country: Italy
facility: Azienda Ospedaliera G. Brotzu - Ospedale Businco
city: Monza
country: Italy
facility: Divisione Universitaria di Onco-Ematologia
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova Dipartimento di Medicina Interna
city: Palermo
country: Italy
facility: Ospedali Riuniti Villa Sofia
city: Gdańsk
country: Poland
facility: Gdański Uniwersytet Medyczny Department of Hematology and Transplantology
city: Kraków
country: Poland
facility: Samodzielny Publiczny Zakład Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie
city: Warszawa
country: Poland
facility: Instytut Hematologii i Transfuzjologii ul. Indiry Gandhi 14 02-776 Warszawa
city: Wrocław
country: Poland
facility: Uniwersyteckie Centrum Kliniczne im. Jana Mikulicza- Radeckiego we Wrocławiu
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
state: Av. Roma
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
state: Avda De Córdoba
city: Barcelona
country: Spain
facility: Hospital Duran i Reynals. Institut Catala d'Oncologia
state: Avinguda De La Granvia De l'Hospitalet, 199-203
city: Carretera De Canyet
country: Spain
facility: Hospital Germans Trias i Pujol-ICO Badalona
state: Barcelona
city: Passeig De La Vall d'Hebron, 119-129
country: Spain
facility: Hospital Universitario Vall d'Hebron
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
state: C. De Villarroel, 170
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
state: Calle Del Dr. Esquerdo
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
state: Ctra. De Colmenar Viejo Km. 9,100
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
state: P.º De San Vicente, 58
city: Av. De Valdecilla, 25
country: Spain
facility: Hospital Universitario Marques de Valdecilla
state: Santander
city: Av. Manuel Siurot
country: Spain
facility: Hospital Universitario Virgen del Rocio
state: Sevilla
Study officials:
affiliation: Medical University of Gdansk
name: Jan M Zaucha, Professor, PhD, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Research and Clinical Innovation Department of the Lacassagne Cancer Center
name: Andrea Gallamini, Professor, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References: