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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medical University Of Gdansk

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

30 Mar 2021 → ongoing

Decision date (initial)

2024-11-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Medical Research Agency

External identifiers

EU CT number

2024-515063-66-00

EudraCT number

2020-002382-33

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Therapy, Safety, Efficacy

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 objectives 4

1. To explore the efficacy in terms of 3-Y PFS, of tipple association (chemotherapy +INRT+ Nivolumab) 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.

Conditions and MedDRA coding

Early stage classical Hodgkin Lymphoma (cHL) without bulky lesions and constitutional symptoms

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

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 < 2.0 mg/dL and/or Creatinine clearance or calculated Creatinine clearance > 40 mL/minute
10. Total bilirubin must be < 2.0 x the upper limit of normal (ULN) unless known Gilbert syndrome
11. ALT or AST must be < 3 x the upper limit of normal.
12. 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.
13. Male patients should agree to practice barrier contraception or to practice abstinence

Exclusion criteria 15

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

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).

Secondary endpoints 4

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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medical University Of Gdansk

Sponsor organisation

Medical University Of Gdansk

Address

Ul. Marii Sklodowskiej-Curie 3a

City

Gdansk

Postcode

80-210

Country

Poland

Scientific contact point

Organisation

Medical University Of Gdansk

Contact name

Study Coordinator

Public contact point

Organisation

Medical University Of Gdansk

Contact name

Study Coordinator

Locations

3 EU/EEA countries · 36 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications