Radiation Free Chemotherapy for Early Hodgkin Lymphoma (RAFTING)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Hodgkin Lymphoma
• Intervention / Treatment: Drug: Nivolumab 10 MG/ML

• Study Type: Interventional
• Enrollment (Anticipated): 160
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jan M Zaucha, Professor, PhD, MD; Phone Number: 0048 58 584 43 40; Email: jzaucha@gumed.edu.pl
• Study Contact Backup: Name: Marta Bednarek, PhD; Phone Number: 0048 58 349 18 85; Email: marta.bednarek@gumed.edu.pl

Study Locations

• Italy
  • Ancona, Italy
    • Not yet recruiting
    • Azienda Ospedaliero - Universitaria Ospedali Riuniti
    • Contact: Guido Gini, MD, PhD
  • Cagliari, Italy
    • Not yet recruiting
    • Azienda Ospedaliera G. Brotzu - Ospedale Businco
    • Contact: Giorgio La Nasa, MD, PhD
  • Monza, Italy
    • Not yet recruiting
    • Divisione Universitaria di Onco-Ematologia
    • Contact: Silvia Bolis, MD, PhD
  • Padova, Italy
    • Not yet recruiting
    • Azienda Ospedaliera di Padova Dipartimento di Medicina Interna
    • Contact: Livio Trentin, MD, PhD
  • Palermo, Italy
    • Not yet recruiting
    • Ospedali Riuniti Villa Sofia
    • Contact: Caterina Patti, MD, PhD
  • P.le Golgi 19
    • Pavia, P.le Golgi 19, Italy, 27100
      • Recruiting
      • Hematology Department IRCCS Policlinico San Matteo
      • Contact: Manuel Gotti, MD, PhD; Phone Number: +39 347 9797989; Email: Ma.Gotti@smatteo.pv.it
  • Piazza OMS, 1
    • Bergamo, Piazza OMS, 1, Italy, 24127
      • Not yet recruiting
      • Ospedale Papa Giovanni XXIII
      • Contact: Alessandro Rambaldi, MD, PhD
  • Via Giuseppe Ripamonti 435
    • Milano, Via Giuseppe Ripamonti 435, Italy, 20141
      • Not yet recruiting
      • Istituto Europeo di Oncologia
      • Contact: Corrado Tarella, MD, PhD
  • Via Michele Coppino, 26
    • Cuneo, Via Michele Coppino, 26, Italy, 12100
      • Not yet recruiting
      • Hematology Department Azienda Ospedaliera S. Croce e Carle
      • Contact: Roberto Sorasio, MD, PhD
  • Via S.Pansini, 5
    • Napoli, Via S.Pansini, 5, Italy, 80131
      • Recruiting
      • Azienda Ospedaliera Universitaria Policlinico Federico II
      • Contact: Marco Picardi, MD, PhD
  • Viale Orazio Flacco, 65
    • Bari, Viale Orazio Flacco, 65, Italy, 70124
      • Not yet recruiting
      • Irccs Istituto Tumori Giovanni Paolo Ii
      • Contact: Attilio Guarini, MD, PhD
  • Viale Oxford, 81
    • Roma, Viale Oxford, 81, Italy, 00133
      • Not yet recruiting
      • Policlinico Università Tor Vergata
      • Contact: Maria Cantonetti, MD, PhD
• Poland
  • Gdańsk, Poland
    • Recruiting
    • Gdański Uniwersytet Medyczny Department of Hematology and Transplantology
    • Contact: Jan M Zaucha, Professor, PhD, MD; Phone Number: 0048 58 584 43 40; Email: jzaucha@gumed.edu.pl
  • Kraków, Poland
    • Not yet recruiting
    • Samodzielny Publiczny Zakład Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie
    • Contact: Agnieszka Giza, PhD, MD
  • Warszawa, Poland
    • Not yet recruiting
    • Instytut Hematologii i Transfuzjologii ul. Indiry Gandhi 14 02-776 Warszawa
    • Contact: Ewa Paszkiewicz-Kozik, PhD, MD
  • Wrocław, Poland
    • Not yet recruiting
    • Uniwersyteckie Centrum Kliniczne im. Jana Mikulicza- Radeckiego we Wrocławiu
    • Contact: Tomasz Wrobel, Professor, PhD, MD; Phone Number: 71 7841764
• Spain
  • Av. Roma
    • Oviedo, Av. Roma, Spain, 33011
      • Not yet recruiting
      • Hospital Universitario Central de Asturias
      • Contact: Ana Pilar Gonzales Rodriguez, MD, PhD
  • Avda De Córdoba
    • Madrid, Avda De Córdoba, Spain, 28041
      • Not yet recruiting
      • Hospital Universitario 12 de Octubre
      • Contact: Antonia Rodriguez-Izquierdo
  • Avinguda De La Granvia De l'Hospitalet, 199-203
    • Barcelona, Avinguda De La Granvia De l'Hospitalet, 199-203, Spain, 08908
      • Not yet recruiting
      • Hospital Duran i Reynals. Institut Catala d'Oncologia
      • Contact: Eva Domingo Domenech, MD, PhD
  • Barcelona
    • Carretera De Canyet, Barcelona, Spain, 08916
      • Not yet recruiting
      • Hospital Germans Trias i Pujol-ICO Badalona
      • Contact: Miriam Moreno Velazquez, MD, PhD
    • Passeig De La Vall d'Hebron, 119-129, Barcelona, Spain, 08035
      • Not yet recruiting
      • Hospital Universitario Vall d'Hebron
      • Contact: Cecilia Carpio, MD, PhD
  • C. De Villarroel, 170
    • Barcelona, C. De Villarroel, 170, Spain, 08036
      • Not yet recruiting
      • Hospital Clinic de Barcelona
      • Contact: Carmen Martinez Munoz, MD, PhD
  • Calle Del Dr. Esquerdo
    • Madrid, Calle Del Dr. Esquerdo, Spain, 28007
      • Not yet recruiting
      • Hospital General Universitario Gregorio Marañon
      • Contact: Mariana Bastos-Oreiro, MD, PhD
  • Ctra. De Colmenar Viejo Km. 9,100
    • Madrid, Ctra. De Colmenar Viejo Km. 9,100, Spain, 28034
      • Not yet recruiting
      • Hospital Universitario Ramón y Cajal
      • Contact: Francisco Javier Lopez Jimenez, MD, PhD
  • P.º De San Vicente, 58
    • Salamanca, P.º De San Vicente, 58, Spain, 37007
      • Not yet recruiting
      • Hospital Universitario de Salamanca
      • Contact: Roman Garcia Sanz, MD, PhD
  • Santander
    • Av. De Valdecilla, 25, Santander, Spain, 39008
      • Not yet recruiting
      • Hospital Universitario Marques de Valdecilla
      • Contact: Javier Nuñez Cespedes, MD, PhD
  • Sevilla
    • Av. Manuel Siurot, Sevilla, Spain, 41013
      • Not yet recruiting
      • Hospital Universitario Virgen del Rocio
      • Contact: Jorge Rodríguez Garcia, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 56 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study group; Nivolumab, total dose 5760 mg milligram	Drug: Nivolumab 10 MG/ML; Nivolumab, 100 mg, 10 mg/ml

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy exploration in terms of 3-Y PFS of chemotherapy alone	To explore the efficacy, in terms of 3-Y PFS of chemotherapy alone in low-risk early-stage I-IIA HL patients, defined by both a low MTV and a negative interim PET after 2 courses of ABVD	During follow-up (36 months) after the end of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy exploration in terms of 3-Y PFS of chemotherapy plus Nivolumab	To explore the efficacy in terms of 3-Y PFS of CMT plus Nivolumab in high-risk early-stage (I-IIA) HL (eHL), defined either by a positive PET- 2 or a high baseline MTV or both	During follow-up (36 months) after the end of treatment
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	To explore the efficacy in terms of 3-Y freedom from 2nd treatment failure (3-Y FF2TF) of chemotherapy followed by radiotherapy "on demand" plus Nivolumab maintenance in patients relapsing with the pattern of "limited relapse" (see below) for the entire group (relapsed and non-relapsed) of low-risk patients (with low MTV and negative PET- 2) high-risk early-stage (I-IIA) HL (eHL), defined either by a positive PET- 2 or a high baseline MTV or both	During follow-up (36 months) after the end of treatment
Safety exploration in terms of 3-Y OS of a treatment with chemotherapy alone	To explore the safety in terms of 3-Y OS of a treatment with chemotherapy alone in low-risk early-stage (I-IIA) HL patients, defined by a low Metabolic Tumor Volume negative interim PET after 2 ABVD courses	During follow-up (36 months) after the end of treatment
Evaluation the ability of cell-free DNA (cfDNA) assay	To evaluate the ability of cell-free DNA (cfDNA) assay to detect an impending relapse during follow-up in low-risk patients treated with chemotherapy alone�k�	During follow-up (36 months) after the end of treatment

Collaborators and Investigators

• Sponsor: Medical University of Gdansk
• Investigators: Principal Investigator: Jan M Zaucha, Professor, PhD, MD, Medical University of Gdansk; Principal Investigator: Andrea Gallamini, Professor, PhD, MD, Research and Clinical Innovation Department of the Lacassagne Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2021
• Primary Completion (Anticipated): September 30, 2022
• Study Completion (Anticipated): July 2, 2026

Study Registration Dates

• First Submitted: April 22, 2021
• First Submitted That Met QC Criteria: April 26, 2021
• First Posted (Actual): April 30, 2021

Study Record Updates

• Last Update Posted (Actual): August 12, 2021
• Last Update Submitted That Met QC Criteria: August 11, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Hodgkin Disease; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: NBK132/1/2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No