Radiation Free Chemotherapy for Early Hodgkin Lymphoma

Hodgkin Lymphoma Clinical Trial

— RAFTING  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04866654
• Other study ID #: NBK132/1/2020
• Status: Recruiting
• Phase: Phase 2
• Start date: March 4, 2021
• Est. completion date: July 2, 2026

Study information

• Verified date: August 2021
• Source: Medical University of Gdansk
• Contact: Jan M Zaucha, Professor, PhD, MD
• Phone: 58 584 43 40
• Email: jzaucha[@]gumed.edu.pl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Est. completion date: July 2, 2026
• Est. primary completion date: September 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hodgkin Disease
• Hodgkin Lymphoma
• Lymphoma

Intervention

Drug:
• Nivolumab 10 MG/ML
Nivolumab, 100 mg, 10 mg/ml

Locations

Country	Name	City	State
Italy	Azienda Ospedaliero - Universitaria Ospedali Riuniti	Ancona
Italy	IRCCS Istituto Tumori Giovanni Paolo II	Bari	Viale Orazio Flacco, 65
Italy	Ospedale Papa Giovanni XXIII	Bergamo	Piazza OMS, 1
Italy	Azienda Ospedaliera G. Brotzu - Ospedale Businco	Cagliari
Italy	Hematology Department Azienda Ospedaliera S. Croce e Carle	Cuneo	Via Michele Coppino, 26
Italy	Istituto Europeo di Oncologia	Milano	Via Giuseppe Ripamonti 435
Italy	Divisione Universitaria di Onco-Ematologia	Monza
Italy	Azienda Ospedaliera Universitaria Policlinico Federico II	Napoli	Via S.Pansini, 5
Italy	Azienda Ospedaliera di Padova Dipartimento di Medicina Interna	Padova
Italy	Ospedali Riuniti Villa Sofia	Palermo
Italy	Hematology Department IRCCS Policlinico San Matteo	Pavia	P.le Golgi 19
Italy	Policlinico Università Tor Vergata	Roma	Viale Oxford, 81
Poland	Gdanski Uniwersytet Medyczny Department of Hematology and Transplantology	Gdansk
Poland	Samodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie	Kraków
Poland	Instytut Hematologii i Transfuzjologii ul. Indiry Gandhi 14 02-776 Warszawa	Warszawa
Poland	Uniwersyteckie Centrum Kliniczne im. Jana Mikulicza- Radeckiego we Wroclawiu	Wroclaw
Spain	Hospital Universitario Marques de Valdecilla	Av. De Valdecilla, 25	Santander
Spain	Hospital Universitario Virgen del Rocio	Av. Manuel Siurot	Sevilla
Spain	Hospital Clinic de Barcelona	Barcelona	C. De Villarroel, 170
Spain	Hospital Duran i Reynals. Institut Catala d'Oncologia	Barcelona	Avinguda De La Granvia De l'Hospitalet, 199-203
Spain	Hospital Germans Trias i Pujol-ICO Badalona	Carretera De Canyet	Barcelona
Spain	Hospital General Universitario Gregorio Marañon	Madrid	Calle Del Dr. Esquerdo
Spain	Hospital Universitario 12 de Octubre	Madrid	Avda De Córdoba
Spain	Hospital Universitario Ramón y Cajal	Madrid	Ctra. De Colmenar Viejo Km. 9,100
Spain	Hospital Universitario Central de Asturias	Oviedo	Av. Roma
Spain	Hospital Universitario Vall d'Hebron	Passeig De La Vall d'Hebron, 119-129	Barcelona
Spain	Hospital Universitario de Salamanca	Salamanca	P.º De San Vicente, 58

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Gdansk

Countries where clinical trial is conducted

Italy,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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