Use of nivolumab (N) followed by chemotherapy: bendamustine, gemcitabine and dexamethasone (BGD) with autologous bone marrow transplantation in patients with Hodgkin’s lymphoma refractory to 1-line therapy.

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

1 Dec 2022 → ongoing

Decision date (initial)

2024-11-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Medical Research Agency

External identifiers

EU CT number

2024-515064-31-00

EudraCT number

2021-002630-17

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

To evaluate the efficacy and safety of the intervention based on early initiation of second-line treatment (Nivolumab) in patients with Hodgkin's lymphoma resistant to previously administered treatment, followed by BGD chemotherapy (2 cycles) and consolidation with autologous transplantation of hematopoietic stem cells (aHCT). Additionally, the predictive value of circulating free DNA of Hodgkin's lymphoma cells measured before autologous transplantation will be assessed.

Secondary objectives 4

1. Percentage of all complete and partial metabolic responses (overall metabolic response rate, OMRR = CMR + CSF after N, BGD, and aHCT treatment.
2. Overall Survival (OS) from the time of initiation of Nivolumab treatment to the time of death from any cause.
3. Percentage of patients among whom aHCT was successfully performed.
4. Tolerance of N-BGD treatment defined as the frequency of adverse events (AEs) with a toxicity level greater than two based on Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. The number of grade 3 and 4 adverse reactions assessed according to CTCAE v. 5.

Conditions and MedDRA coding

Refractory / relapsed Hodgkin's lymphoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Patients with recurrence of previously confirmed histopathologically confirmed classical Hodgkin's lymphoma based on the local pathology report according to the WHO 2016 classification, after the first line of treatment initially diagnosed in stage IIA but with a large metabolic tumor volume or the presence of a massive lesion (>10cm) or diagnosed in stage IIB- IV OR Patients with primary refractory classical Hodgkin's lymphoma in stage IIA with a large metabolic tumor volume (>147 ml) or the presence of a massive lesion (>10 cm) or in stage IIB-IV. Primary resistance to treatment will be defined by a positive iPET2 test (Deauville scale scores 4 and 5) performed after the 2nd cycle of first-line chemotherapy; and in patients with a negative iPET2 test result (Deauville scale scores 1, 2, 3) the occurrence of active disease confirmed by PET-CT within three months of the end of first-line chemotherapy.
2. Evaluation of disease advancement by PET examination at diagnosis.
3. Age ≥18 years old
4. ECOG 0-2
5. Presence of at least one measurable change
6. Consent to effective contraception during the study using contraception for 14 months for women and 11 months for men after the last dose of immuno-chemotherapy
7. In women of childbearing age, a negative serum pregnancy test result at screening and consent to use highly effective methods of contraception during the study and for 14 months after the last dose of chemotherapy (except for patients over 50 years of age with natural amenorrhea for a period of at least 12 months or after bilateral salpingoophorectomy or hysterectomy).
8. Signing consent to participate in the clinical trial

Exclusion criteria 14

1. Non-classical form of Hodgkin's lymphoma
2. Performance status according to ECOG>2
3. Failure to perform PET scans during induction treatment in accordance with the inclusion criteria
4. Transformation of Hodgkin's lymphoma into another lymphoma
5. Central nervous system involvement
6. Medical contraindications or patient's refusal to consolidate BGD rescue treatment with aHCT
7. Other cancer - active form or less than 5 years from cure
8. Uncontrolled diabetes
9. Heart failure NYHA>2 or LVEF<45%
10. Liver failure (bilirubin 1.5 x ULN, SGOT > 5 x ULN) if unrelated to lymphoma, and Gilbert's syndrome
11. HIV infection, active HBV, HCV, CMV infection. In the case of hepatitis B infection and the presence of abHBc, it is necessary to evaluate the PCR DNA of the virus and start prophylactic treatment in accordance with the advice of an infectious disease doctor.
12. Pregnancy or breastfeeding
13. Known hypersensitivity to any of the drugs used in the treatment.
14. The patient is unable to sign the informed consent form to participate in the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Complete Metabolic Remission (CMR) rate after 2 cycles of BGD preceded by 3 administrations of Nivolumab (N).
2. PFS, which is the time from N treatment initiation to progression (PD) or death, regardless of cause.

Secondary endpoints 5

1. Percentage of all complete and partial metabolic responses (overall metabolic response rate, OMRR = CMR + CSF after N, BGD, and aHCT treatment.
2. Overall Survival (OS) from the time of initiation of Nivolumab treatment to the time of death from any cause.
3. Percentage of patients among whom aHCT was successfully performed.
4. Tolerance of N-BGD treatment defined as the frequency of adverse events (AEs) with a toxicity level greater than two based on Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.
5. The number of grade 3 and 4 adverse reactions assessed according to CTCAE v. 5.

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

1 EU/EEA country · 9 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 4 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