PET Guided Dose Reduction for InvOlved Site Radiotherapy In Early sTage Unfavourable Hodgkin Lymphoma

Official title

PET Guided Dose Reduction for InvOlved Site Radiotherapy In Early sTage Unfavourable Hodgkin Lymphoma: a Randomized, Phase III, Non-inferiority studY (PRIORITY Study)

Overview

The final analysis of GHSG HD11 study (not PET driven) showed that 30 Gy IFRT still remains the standard dose after 4 ABVD. Early PET negativity might allow safe radiation de-escalation in patients achieving a metabolic complete response after 2 ABVD. The aim of Priority trial is to explore whether radiotherapy could be safely deescalated to 20 Gy without loss of efficacy in patients treated with four cycles of ABVD who achieved complete metabolic response after the first two cycles.

Interventions

• Radiation 20 Gy Involved site radiotherapy
  Total dose 20 Gy Involved site radiotherapy
• Radiation 30 Gy Involved site radiotherapy
  Total dose 30 Gy Involved site radiotherapy

Primary outcome measures

• To evaluate if de-escalated ISRT dose (20 Gy) is not inferior to conventional ISRT dose (30 Gy) in terms of PFS in patients with newly diagnosed early-stage unfavourable HL achieving a complete metabolic response (DS 1-3) after 2 ABVD cycle [Time frame: From the date of randomization to documented relapse, progression or to the patient's death as a result of any causes (up to 82 months).]

Secondary outcome measures (5)

• To compare OS rates between de-escalated ISRT dose (20 Gy) and conventional ISRT dose (30 Gy) in patients with newly diagnosed early-stage unfavourable HL achieving a complete metabolic response (DS 1-3) after 2 ABVD cycles; [Time frame: From the time of randomization to death from any cause (up to 82 months)]
• To evaluate PFS for the whole population [Time frame: From the date of consent to documented relapse, progression or death from any cause (up to 84 months)]
• To evaluate OS for the whole population [Time frame: From the date of consent to death from any cause (up to 84 months)]
• To describe pattern of failure "in field", "marginal field", "out of field" relapse after conventional and reduced ISRT; [Time frame: From the date of consent to death from any cause (up to 84 months)]
• To report details on RT treatment volumes and dose distributions and to estimate the dose received by the organs at risk (OARs) in the two treatment arms [Time frame: At time of radiotherapy (about 4 months from chemotherapy start)]

Eligibility criteria

Inclusion criteria

• Age ≥18 years;
• Histologically confirmed classical HL stage I, II unfavorable according to GHSG criteria;
• Patient with any nodal mass ≥ than 10 cm can be included
• No previous treatment for Hodgkin lymphoma;
• ECOG performance status 0 to 2;
• Presence of FDG-avid lymphoma lesions on baseline PET scan;
• Subject understands and voluntarily signs the informed consent form approved by the Independent Ethics Committee (IEC), prior to the initiation of any screening or study-specific procedures;
• Adequate organ and marrow function as defined below:

• absolute neutrophil count > 1.0 x109/L
• platelet count > 75 x109/L
• Total bilirubin < 2 mg/dl without a pattern consistent with Gilbert's syndrome
• Aspartate Transaminase and Alanine Transaminase (AST/ALT) < 3.0 X institutional Upper Limits of Normality (ULN)
• Creatinine within normal institutional limits or creatinine clearance > 50 mL/min
• Women of childbearing potential must agree to use a highly effective method of contraception (oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device) from the signature of informed consent until six months after the last dose of treatment;
• Men must agree to use a highly effective method of contraception (barrier contraception or abstinence, when this is in line with the usual lifestyle of the subject) from the signature of informed consent until six months after the last dose of treatment;
• Women of childbearing potential must have a negative serum pregnancy test at screening.

Exclusion criteria

• Patients who meet any of the following criteria are not eligible to enroll:
• Stage II B- III- IV
• Hodgkin Lymphoma as "composite lymphoma" or nodular lymphocyte prevalence histological subtype
• Active HBV and HCV infection
• HIV seropositivity
• Pre-treatment with chemotherapy or radiation therapy
• Malignant disease within the last 5 years (excluding basal skin tumors and carcinoma in situ of the cervix)
• Women who are pregnant or breast feeding
• Absence of FDG-avid lymphoma lesions on baseline PET scan
• Significant history of neurologic, psychiatric, endocrinological, metabolic, immunologic, or hepatic disease that would preclude participation in the study or compromise ability to give informed consent.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Italy · 38 centers

• A.O.U. SS. Antonio e Biagio e C. Arrigo - S.C.D.U. Ematologia — Alessandria
• A.O.R.N. G Moscati - U.O.C. Ematologia e Terapie cellulari avanzate — Avellino
• IRCCS Centro Riferimento Oncologico - S.O.C. Oncologia medica e dei tumori immuno-correlat — Aviano
• ASST Papa Giovanni XXIII - S.C. Ematologia — Bergamo
• Clinica Humanitas Gavazzeni - U.O. Oncologia Medica — Bergamo
• ASST Spedali Civili - S.C. Ematologia — Brescia
• ARNAS "Brotzu" P.O. Businco - S.C. Ematologia e TMO — Cagliari
• I.R.C.C.S. Istituto di Candiolo - FPO — Candiolo
• … and 30 more centers

Identifiers

NCT: NCT07256158 · FIL_PRIORITY

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗