INDIE: Phase II Trial of Individualized Immunotherapy in Early-Stage Unfavorable Classical Hodgkin Lymphoma

Sponsor

University of Cologne (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04837859

Collaborator

(none)

120

Enrollment

Location

Arms

Anticipated Duration (Months)

2.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The aim of the trial is to establish an individualized first-line treatment incorporating checkpoint inhibition for early-stage unfavorable cHL, which is effective and well tolerated.

Condition or Disease	Intervention/Treatment	Phase
Classical Hodgkin Lymphoma	Drug: Tislelizumab	Phase 2

Detailed Description

Programmed cell death protein-1 (PD-1) blockade is highly effective and well tolerated in relapsed or refractory cHL and has also demonstrated efficacy in the first-line treatment of cHL in combination with doxorubicin, vinblastine, and dacarbazine (AVD) in the phase II GHSG NIVAHL trial. A relevant proportion of patients achieved an early metabolic complete remission (CR) with anti-PD-1 monotherapy and might not require standard chemo- or radiotherapy. Limiting therapy-associated short- and long-term side effects of these conventional treatments including impaired quality of life, second primary malignancies or organ damage is of utmost importance in the predominantly young cHL patients. This trial will hence further reduce treatment intensity and provide a chemo- and radiotherapy-free therapy to optimally responding patients.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase II Trial of Individualized Immunotherapy in Early-Stage Unfavorable Classical Hodgkin Lymphoma

Anticipated Study Start Date :

Dec 1, 2022

Anticipated Primary Completion Date :

Dec 1, 2024

Anticipated Study Completion Date :

Dec 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A age 18-60 Patients at the age of 18-60 years at enrollment will receive 2 initial doses of 200 mg tislelizumab in 21-day intervals followed by an interim positron emission tomography (PET-2). Following a PET-guided approach, patients with a negative PET-2 (i.e. Deauville score 1-3) according to central review will continue receiving tislelizumab for another 4 doses of 300 mg in 28-day intervals. Patients with a positive PET-2 (i.e. Deauville score >3) will receive 4 cycles of combined 300 mg tislelizumab on day 1 and AVD chemotherapy on day 1 and 15 in 28-day cycles (4x T-AVD). For all patients, 30 Gy involved-site radiotherapy (IS-RT) will only be applied in case of PET positivity after completion of (chemo-) immunotherapy.	Drug: Tislelizumab age 18-60: Tislelizumab alone or in combination with AVD (depending on the PET result after 2x Tislelizumab) followed by IS-RT if PET positive resudues after the end of Tis or Tis-AVD age 60+: Tislelizumab alone or in combination with AVD (depending on the PET result after 2x Tislelizumab) followed by IS-RT for all patients
Experimental: Arm B Age 60+ Patients above the age of 60 years will be enrolled in a separate, exploratory cohort and receive PET-guided treatment with tislelizumab or T-AVD as described above. However, all patients in the exploratory cohort for older patients will receive consolidating 30 Gy IS-RT.	Drug: Tislelizumab age 18-60: Tislelizumab alone or in combination with AVD (depending on the PET result after 2x Tislelizumab) followed by IS-RT if PET positive resudues after the end of Tis or Tis-AVD age 60+: Tislelizumab alone or in combination with AVD (depending on the PET result after 2x Tislelizumab) followed by IS-RT for all patients

Arm

Intervention/Treatment

Experimental: Arm A age 18-60

Patients at the age of 18-60 years at enrollment will receive 2 initial doses of 200 mg tislelizumab in 21-day intervals followed by an interim positron emission tomography (PET-2). Following a PET-guided approach, patients with a negative PET-2 (i.e. Deauville score 1-3) according to central review will continue receiving tislelizumab for another 4 doses of 300 mg in 28-day intervals. Patients with a positive PET-2 (i.e. Deauville score >3) will receive 4 cycles of combined 300 mg tislelizumab on day 1 and AVD chemotherapy on day 1 and 15 in 28-day cycles (4x T-AVD). For all patients, 30 Gy involved-site radiotherapy (IS-RT) will only be applied in case of PET positivity after completion of (chemo-) immunotherapy.

Drug: Tislelizumab

age 18-60: Tislelizumab alone or in combination with AVD (depending on the PET result after 2x Tislelizumab) followed by IS-RT if PET positive resudues after the end of Tis or Tis-AVD age 60+: Tislelizumab alone or in combination with AVD (depending on the PET result after 2x Tislelizumab) followed by IS-RT for all patients

Experimental: Arm B Age 60+

Patients above the age of 60 years will be enrolled in a separate, exploratory cohort and receive PET-guided treatment with tislelizumab or T-AVD as described above. However, all patients in the exploratory cohort for older patients will receive consolidating 30 Gy IS-RT.

Drug: Tislelizumab

Outcome Measures

Primary Outcome Measures

Progression Free Survival [1 year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 18-60 for the main trial cohort
Age ≥ 61 years and eligible for AVD as determined by CIRS-G score and investigator for the exploratory cohort
First diagnosis of treatment-naïve cHL
Early-stage unfavorable disease (i.e. stage IA, IB and IIA with risk factors a-d, stage IIB with risk factors c-d):

large mediastinal mass
extranodal lesion(s)
elevated erythrocyte sedimentation rate
≥ 3 nodal areas

Exclusion Criteria:

Presence of nodular-lymphocyte predominant Hodgkin lymphoma, grey-zone lymphoma and/or central nervous system involvement of lymphoma

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	1st Department of Medicine, Cologne University Hospital	Cologne		Germany

Sponsors and Collaborators

University of Cologne

Investigators

Principal Investigator: Andreas Engert, Prof., 1st Department of Medicine, Cologne Universit Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Prof. Dr. Andreas Engert, Prof., University of Cologne

ClinicalTrials.gov Identifier:

NCT04837859

Other Study ID Numbers:

Uni-Koeln-4470

First Posted:

Apr 8, 2021

Last Update Posted:

Aug 8, 2022

Last Verified:

Aug 1, 2022

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Lymphoma

Hodgkin Disease

Study Results

No Results Posted as of Aug 8, 2022