Early stage classical Hodgkin Lymphoma (cHL) without bulky lesions and constitutional symptoms MedDRA version: 20.1 Level: LLT Classification code 10080208 Term: Classical Hodgkin lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Medical University of Gdansk
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patients aged 18-70. 2. Treatment-naïve, classical HL patients with Ann Arbor stage I or II A non-bulky disease stratified according to modified EORTC Criteria (refer to Appendix A); 3. 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]; 4. ECOG performance status 0-2 5. Hemoglobin must be > 8 gr./dL 6. Absolute neutrophil count = 1,000/µL 7. Platelet count = 100,000/µL 8. Voluntary written consent to take part to the study 9. Serum Creatinine 40 mL/minute 10. Total bilirubin must be =65 years) no F.1.3.1 Number of subjects for this age range 18
Exclusion criteria
Exclusion criteria: 1. Composite lymphoma or nodular lymphocyte-predominant Hodgkin lymphoma; 2. Bulky disease (Lugano 2014 definition: single or conglomerated nodal mass with the largest diameter measuring 10 or more centimeters); 3. B symptoms; 4. Extra nodal site involved by disease; 5. 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; 6. Uncompensated diabetes mellitus requiring insulin therapy; 7. Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol; 8. Known human immunodeficiency virus (HIV) infection with a positive search for HIV antigens by immunoblot and/or circulating copies of HIV-RNA; 9. Active hepatitis B with circulating copies of HBV-DNA, or active hepatitis C infection with circulating copies of HCV-RNA; 10. Severely impaired, lung and renal function; 11. 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; 12. Active autoimmune disorder in treatment with immunosuppressive drugs 13. A left-ventricular ejection fraction < 50%; 14. Myocardial infarction within 2 years of study entry. 15. Pregnancy or lactation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): 1. To evaluate the overall efficacy in terms of 3-Y PFS equal or superior to 90% , defined as the time from registration until first occurrence of disease progression or relapse, or death for any reason of chemotherapy alone in non-bulky stage I-IIA Hodgkin Lymphoma (eHL), patients with a very low risk of treatment failure, as defined by both a low Metabolic Tumor Volume (MTV) and a negative interim PET after 2 ABVD cycle (PET-2).;Timepoint(s) of evaluation of this end point: During follow-up after the end of treatment ;Main Objective: 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 Objective: 1.To explore the efficacy in terms of 3-Y PFS, of tipple association (chemotherapy +INRT+ NivlumabNivolumab) in high-risk early-stage (I-IIA) HL (eHL), defined either by a positive PET-2 or a high baseline MTV or both. 2.To explore the efficacy in terms of 3-Y freedom from 2nd treatment failure (3-Y FF2TF) of chemotherapy followed by INRT “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) 3.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. 4.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. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. To explore the efficacy in terms of 3-Y PFS defined as the time from registration until first occurrence of disease progression or relapse, or death for any reason of CMT plus Nivolumab in high-risk eHL, defined either by a positive PET-2 or a high baseline MTV or both. 2. To evaluate the efficacy, in terms of three-year freedom from second treatment Failure (3-Y FF2TF), measured from the date of registration to the date of second relapse after radiotherapy “on demand” to rescue patients relapsed after CT alone with the pattern of “limited relapse” for the entire group (relapsed and non-relapsed) of low-risk patients (with low MTV and negative PET2). 3. To evaluate the safety, in terms of 3-Y OS, defined as the time from enrollment until death for any reason of the delayed radiotherapy (RT ,,on demand”) followe by Nivolumab maintenance in rescuing patients who relapsed after chemotherapy alone with the pattern of ,,limited relapse”. 4. Overall accuracy, sensitivity, specificity, negative predictive value and positive predictive value of cell-free DNA to detect an impending relapse during follow-up of patients treated with chemotherapy alone ;Timepoint(s) of evaluation of this end point: During follow-up after the end of treatment | — |
Countries
Italy, Poland, Spain
Contacts
Public ContactJan Maciej Zaucha
Medical University of Gdansk
Outcome results
None listed