Radiation Free Chemotherapy for Early Hodgkin Lymphoma (RAFTING)
Primary Purpose
Hodgkin Lymphoma
Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Nivolumab 10 MG/ML
Sponsored by
About this trial
This is an interventional treatment trial for Hodgkin Lymphoma
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.
Sites / Locations
- Hematology Department IRCCS Policlinico San MatteoRecruiting
- Ospedale Papa Giovanni XXIII
- Istituto Europeo di Oncologia
- Hematology Department Azienda Ospedaliera S. Croce e Carle
- Azienda Ospedaliera Universitaria Policlinico Federico IIRecruiting
- IRCCS Istituto Tumori Giovanni Paolo II
- Policlinico Università Tor Vergata
- Azienda Ospedaliero - Universitaria Ospedali Riuniti
- Azienda Ospedaliera G. Brotzu - Ospedale Businco
- Divisione Universitaria di Onco-Ematologia
- Azienda Ospedaliera di Padova Dipartimento di Medicina Interna
- Ospedali Riuniti Villa Sofia
- Gdański Uniwersytet Medyczny Department of Hematology and TransplantologyRecruiting
- Samodzielny Publiczny Zakład Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie
- Instytut Hematologii i Transfuzjologii ul. Indiry Gandhi 14 02-776 Warszawa
- Uniwersyteckie Centrum Kliniczne im. Jana Mikulicza- Radeckiego we Wrocławiu
- Hospital Universitario Central de Asturias
- Hospital Universitario 12 de Octubre
- Hospital Duran i Reynals. Institut Catala d'Oncologia
- Hospital Germans Trias i Pujol-ICO Badalona
- Hospital Universitario Vall d'Hebron
- Hospital Clinic de Barcelona
- Hospital General Universitario Gregorio Marañon
- Hospital Universitario Ramón y Cajal
- Hospital Universitario de Salamanca
- Hospital Universitario Marques de Valdecilla
- Hospital Universitario Virgen del Rocio
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Study group
Arm Description
Nivolumab, total dose 5760 mg milligram
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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
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
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
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�
Full Information
NCT ID
NCT04866654
First Posted
April 22, 2021
Last Updated
August 11, 2021
Sponsor
Medical University of Gdansk
1. Study Identification
Unique Protocol Identification Number
NCT04866654
Brief Title
Radiation Free Chemotherapy for Early Hodgkin Lymphoma
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2021
Overall Recruitment Status
Recruiting
Study Start Date
March 4, 2021 (Actual)
Primary Completion Date
September 30, 2022 (Anticipated)
Study Completion Date
July 2, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Medical University of Gdansk
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hodgkin Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
160 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Study group
Arm Type
Experimental
Arm Description
Nivolumab, total dose 5760 mg milligram
Intervention Type
Drug
Intervention Name(s)
Nivolumab 10 MG/ML
Intervention Description
Nivolumab, 100 mg, 10 mg/ml
Primary Outcome Measure Information:
Title
Efficacy exploration in terms of 3-Y PFS of chemotherapy alone
Description
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
Time Frame
During follow-up (36 months) after the end of treatment
Secondary Outcome Measure Information:
Title
Efficacy exploration in terms of 3-Y PFS of chemotherapy plus Nivolumab
Description
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
Time Frame
During follow-up (36 months) after the end of treatment
Title
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
Description
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
Time Frame
During follow-up (36 months) after the end of treatment
Title
Safety exploration in terms of 3-Y OS of a treatment with chemotherapy alone
Description
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
Time Frame
During follow-up (36 months) after the end of treatment
Title
Evaluation the ability of cell-free DNA (cfDNA) assay
Description
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�
Time Frame
During follow-up (36 months) after the end of treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jan M Zaucha, Professor, PhD, MD
Phone
58 584 43 40
Ext
0048
Email
jzaucha@gumed.edu.pl
First Name & Middle Initial & Last Name or Official Title & Degree
Marta Bednarek, PhD
Phone
58 349 18 85
Ext
0048
Email
marta.bednarek@gumed.edu.pl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jan M Zaucha, Professor, PhD, MD
Organizational Affiliation
Medical University of Gdansk
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Andrea Gallamini, Professor, PhD, MD
Organizational Affiliation
Research and Clinical Innovation Department of the Lacassagne Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hematology Department IRCCS Policlinico San Matteo
City
Pavia
State/Province
P.le Golgi 19
ZIP/Postal Code
27100
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Manuel Gotti, MD, PhD
Phone
347 9797989
Ext
+39
Email
Ma.Gotti@smatteo.pv.it
Facility Name
Ospedale Papa Giovanni XXIII
City
Bergamo
State/Province
Piazza OMS, 1
ZIP/Postal Code
24127
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alessandro Rambaldi, MD, PhD
Facility Name
Istituto Europeo di Oncologia
City
Milano
State/Province
Via Giuseppe Ripamonti 435
ZIP/Postal Code
20141
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Corrado Tarella, MD, PhD
Facility Name
Hematology Department Azienda Ospedaliera S. Croce e Carle
City
Cuneo
State/Province
Via Michele Coppino, 26
ZIP/Postal Code
12100
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Roberto Sorasio, MD, PhD
Facility Name
Azienda Ospedaliera Universitaria Policlinico Federico II
City
Napoli
State/Province
Via S.Pansini, 5
ZIP/Postal Code
80131
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marco Picardi, MD, PhD
Facility Name
IRCCS Istituto Tumori Giovanni Paolo II
City
Bari
State/Province
Viale Orazio Flacco, 65
ZIP/Postal Code
70124
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Attilio Guarini, MD, PhD
Facility Name
Policlinico Università Tor Vergata
City
Roma
State/Province
Viale Oxford, 81
ZIP/Postal Code
00133
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maria Cantonetti, MD, PhD
Facility Name
Azienda Ospedaliero - Universitaria Ospedali Riuniti
City
Ancona
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Guido Gini, MD, PhD
Facility Name
Azienda Ospedaliera G. Brotzu - Ospedale Businco
City
Cagliari
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Giorgio La Nasa, MD, PhD
Facility Name
Divisione Universitaria di Onco-Ematologia
City
Monza
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Silvia Bolis, MD, PhD
Facility Name
Azienda Ospedaliera di Padova Dipartimento di Medicina Interna
City
Padova
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Livio Trentin, MD, PhD
Facility Name
Ospedali Riuniti Villa Sofia
City
Palermo
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Caterina Patti, MD, PhD
Facility Name
Gdański Uniwersytet Medyczny Department of Hematology and Transplantology
City
Gdańsk
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jan M Zaucha, Professor, PhD, MD
Phone
58 584 43 40
Ext
0048
Email
jzaucha@gumed.edu.pl
Facility Name
Samodzielny Publiczny Zakład Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie
City
Kraków
Country
Poland
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Agnieszka Giza, PhD, MD
Facility Name
Instytut Hematologii i Transfuzjologii ul. Indiry Gandhi 14 02-776 Warszawa
City
Warszawa
Country
Poland
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ewa Paszkiewicz-Kozik, PhD, MD
Facility Name
Uniwersyteckie Centrum Kliniczne im. Jana Mikulicza- Radeckiego we Wrocławiu
City
Wrocław
Country
Poland
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tomasz Wrobel, Professor, PhD, MD
Phone
71 7841764
Facility Name
Hospital Universitario Central de Asturias
City
Oviedo
State/Province
Av. Roma
ZIP/Postal Code
33011
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ana Pilar Gonzales Rodriguez, MD, PhD
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
State/Province
Avda De Córdoba
ZIP/Postal Code
28041
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antonia Rodriguez-Izquierdo
Facility Name
Hospital Duran i Reynals. Institut Catala d'Oncologia
City
Barcelona
State/Province
Avinguda De La Granvia De l'Hospitalet, 199-203
ZIP/Postal Code
08908
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eva Domingo Domenech, MD, PhD
Facility Name
Hospital Germans Trias i Pujol-ICO Badalona
City
Carretera De Canyet
State/Province
Barcelona
ZIP/Postal Code
08916
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Miriam Moreno Velazquez, MD, PhD
Facility Name
Hospital Universitario Vall d'Hebron
City
Passeig De La Vall d'Hebron, 119-129
State/Province
Barcelona
ZIP/Postal Code
08035
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cecilia Carpio, MD, PhD
Facility Name
Hospital Clinic de Barcelona
City
Barcelona
State/Province
C. De Villarroel, 170
ZIP/Postal Code
08036
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carmen Martinez Munoz, MD, PhD
Facility Name
Hospital General Universitario Gregorio Marañon
City
Madrid
State/Province
Calle Del Dr. Esquerdo
ZIP/Postal Code
28007
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mariana Bastos-Oreiro, MD, PhD
Facility Name
Hospital Universitario Ramón y Cajal
City
Madrid
State/Province
Ctra. De Colmenar Viejo Km. 9,100
ZIP/Postal Code
28034
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Francisco Javier Lopez Jimenez, MD, PhD
Facility Name
Hospital Universitario de Salamanca
City
Salamanca
State/Province
P.º De San Vicente, 58
ZIP/Postal Code
37007
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Roman Garcia Sanz, MD, PhD
Facility Name
Hospital Universitario Marques de Valdecilla
City
Av. De Valdecilla, 25
State/Province
Santander
ZIP/Postal Code
39008
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Javier Nuñez Cespedes, MD, PhD
Facility Name
Hospital Universitario Virgen del Rocio
City
Av. Manuel Siurot
State/Province
Sevilla
ZIP/Postal Code
41013
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jorge Rodríguez Garcia, MD, PhD
12. IPD Sharing Statement
Plan to Share IPD
No
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Radiation Free Chemotherapy for Early Hodgkin Lymphoma
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