A phase-II academic trial testing, in two parallel non-randomized cohorts, the combination of ruxolitinib (JAK1/2 inhibitor) with brentuximab or nivolumab in relapsed or refractory classical Hodgkin lymphoma (cHL)

Phase 1

Active, not recruiting

• Conditions: Patients with relapsed or refractory cHL that has not responded to, or has progressed after, the previous treatment; Therapeutic area: Diseases [C] - Cancer [C04]; MedDRA version: 20.0Level: LLTClassification code 10020328Term: Hodgkin's lymphomaSystem Organ Class: 100000004864

• Registration Number: EUCTR2019-003084-21-IT
• Lead Sponsor: PROF.BRUNANGELO FALINI, DR.ENRICO TIACCI. DIPARTIMENTO DI MEDICINA, UNIVERSITA' DI PERUGIA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-06-17
• Last Update Posted: 2 March 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 27

Inclusion Criteria

Cohort-1: ruxolitinib + brentuximab
1.Adult patients with CD30+ cHL relapsed or refractory after autologous stem cell transplantation (ASCT), or after at least two previous lines of treatment if ASCT or polichemotherapy do not represent treatment options (as per AIFA label of brentuximab). Patients must also fulfill other specific inclusion and exclusion criteria described below (Additional inclusion and exclusion criteria).
[2.Even when fulfilling the criteria of point 1 above, patients cannot be enrolled if:
i)They had previously received an allotransplant (as they would be blocked by the AIFA registry for brentuximab);
ii)or they can receive less than 6 infusions of brentuximab through the AIFA registry (due to previous infusions of the drugs through the registry);
iii)or they had progressed on brentuximab after activating the AIFA registry for this drug (because progression on brentuximab recorded in the AIFA registry would block further requests of the drug through this registry).
3.If complying with the criteria of points 1 and 2 above, patients progressing after previous treatment in Cohort-2 may be enrolled in Cohort-1 upon decision of the Sponsor in conjunction with the clinical investigator(s).
4.If complying with the criteria of points 1 and 2 above, patients taken off Cohort-2 due to important toxicity from nivolumab may be enrolled in Cohort-1, upon decision of the Sponsor in conjunction with the clinical investigator(s), as long as they have not responded (i.e., no PR nor CR) to the treatment received in Cohort-2.

Cohort 2: ruxolitinib + nivolumab
1.Adult patients with relapsed or refractory cHL previously treated with both ASCT and brentuximab (as per AIFA label of nivolumab). Patients must also fulfill other specific inclusion and exclusion criteria described below (see below section Additional inclusion and exclusion criteria).
2.Patients fulfilling the criteria of point 1 above can be enrolled even if:
i)They had previously received an allotransplant (which does not block the AIFA registry for nivolumab);
ii)They had progressed on nivolumab before activating the AIFA registry for this drug (as they might benefit from combining ruxolitinib to nivolumab). However, even if fulfilling the criteria of point 1 above, patients cannot be enrolled if they progressed on nivolumab after activating the AIFA registry for this drug (because progression on nivolumab recorded in the AIFA registry would block further requests of the drug through this registry).
3.If complying with the criteria of points 1 and 2 above, patients progressing after previous treatment in Cohort-1 may be enrolled in Cohort-2 upon decision of the Sponsor in conjunction with the clinical investigator(s).
4.If complying with the criteria of points 1 and 2 above, patients taken off Cohort-1 due to important toxicity from brentuximab may be enrolled in Cohort-2, upon decision of the Sponsor in conjunction with the clinical investigator(s), as long as they have not responded (i.e., no PR nor CR) to the treatment received in Cohort-1.
Additional inclusion criteria (for both cohorts, see the specific section of the protocol)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 19
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8

Exclusion Criteria

Cohort-1: ruxolitinib + brentuximab
2.Patients cannot be enrolled if:
i)They had previously received an allotransplant (as they would be blocked by the AIFA registry for brentuximab);
ii)or they can receive less than 6 infusions of brentuximab through the AIFA registry (due to previous infusions of the drugs through the registry);
iii)or they had progressed on brentuximab after activating the AIFA registry for this drug (because progression on brentuximab recorded in the AIFA registry would block further requests of the drug through this registry). However, patients fulfilling the criteria of point 1 above can be enrolled if they progressed on brentuximab before activating the AIFA registry (as no record of progression would be present in this registry and the patients might benefit from combining ruxolitinib to brentuximab).
Cohort-2: ruxolitinib + nivolumab
2. ii) Patients cannot be enrolled if they progressed on nivolumab after activating the AIFA registry for this drug (because progression on nivolumab recorded in the AIFA registry would block further requests of the drug through this registry).

Additional exclusion criteria (for both cohorts, except where noted):
1.Previous treatment of cHL with ruxolitinib or another JAK inhibitor received before enrollment in the trial
2.Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate absorption. Patients must be able to swallow capsules.
3.CNS involvement by lymphoma
4.Currently uncontrolled active infection
5.Other severe, acute or chronic medical or psychiatric condition or laboratory abnormality that may, in the judgment of the clinical investigator and/or the Sponsor, increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, or may make the patient inappropriate for entry into this study
6.Pregnant or lactating females, or patients who are not willing to use an adequate method of birth control until 6 month after the last dose of brentuximab or nivolumab
7.Inability to comply with other requirements of the protocol
8.[for Cohort-2 only] Symptomatic interstitial lung disease or active autoimmune disease (except for vitiligo, type-1 diabetes, hypothyroidism secondary to autoimmune thyroiditis requiring hormonal replacement therapy, and psoriasis not requiring systemic treatment), as per AIFA registry of nivolumab
9.[for Cohort-2 only] Therapy with systemic immunosuppressive agents (which would be blocked by the AIFA registry of nivolumab, except for doses = 10 mg/day of prednisone or equivalent corticosteroids) must have been stopped since at least 2 weeks

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified