Non-Hodgkin Lymphom

Short title: AGMT_NHL-15B

Title: Phase II single-arm „window-of-opportunity“ study of a combination of obinutuzumab (GA-101) and venetoclax (ABT-199) in relapsed or refractory diffuse large B-cell lymphoma (DLBCL)

Status: open

Start: January 2017

Coordinating Investigator: Univ. Prof. Dr. Ulrich Jäger

EudraCT Number: 2016-001760-10

ClinicalTrialsID: NCT02987400

Number of patients: 21

Sponsor: AGMT gemeinnützige GmbH

Obinutuzumab is given i.v. at a dose of 1000 mg on days 1, 8, 15 in cycle 1 and on day 1 of each following cycle. Venetoclax is given at 800mg daily p.o. One cycle is 21 days. This combination treatment is repeated for up to 3 cycles. Eligible patients will then proceed to stem cell transplantation (in some patients stem cells were already harvested successfully).

A 9 cycles (27 weeks) maintenance phase with obinutuzumab and venetoclax will be given in patients ineligible for transplant.

The study had a 6 patient run-in phase to determine safety and to adjust treatment. A futility analysis is conducted when the first 10 patients have been evaluated for response: If at least two patients had an objective response (CR or PR) the study will be continued.

Short title: DSHNHL 2015-1_NIVEAU

Title: Improvement of Outcome in Elderly Patients or Patients Not Eligible for High-dose Chemotherapy With Aggressive NHL in First Relapse/Progression by Adding Nivolumab to Gemcitabine, Oxaliplatin Plus Rituximab in Case of B-cell Lymphoma

Status: open

Start: September 2019 (in Austria)

Coordinating Investigator: Univ. Prof. Dr. Ulrich Jäger

EudraCT Number: 2016-002272-27

ClinicalTrialsID: NCT03366272

Number of patients: 388 (international)

Sponsor: University Hospital, Saarland; AGMT Sponsor representative in Austria

This trial is designed as an international, multicentre, randomised, open-label, treatment optimisation study, preceded by safety run-in phases conducted for B-cell and T-cell lymphoma separately.

Aim of the phase-III trial is to test whether prognosis of patients with relapsed or refractory aggressive Non-Hodgkin Lymphoma not eligible for neither autologous nor allogeneic stem cell transplantation can be improved by combining nivolumab with (R)-GemOx.

All patients with  first relapse or progression of an aggressive Non-Hodgkin’s lymphoma aged older than 65 years or older than 18 years with HCT-CI score > 2 are eligible for this study irrespective of their gender or stage of disease. There is no upper limit of age. Also patients not eligible neither autologous nor allogeneic stem cell transplantation are eligible for this study.

The duration of therapy according to study protocol ranges between 16 and 52 weeks. Patients randomised to receive eight 2-week cycles of (R)-GemOx are 16 weeks on therapy. Patients randomised to receive eight 2-week cycles nivolumab plus (R)-GemOx followed by 18 2-week applications of nivolumab are 52 weeks on treatment.

Follow-up observation within the study will end for all patients presumably in Q4/2024, which is 2 years after inclusion of the last patient. Thus duration within the clinical study will last at least 2 years for the individual patient.

Short title: ORACLE (OA-CL-LYM-LYSARC-13134)

Title: Randomized Phase 3 Study evaluating the Efficacy and the Safety of Oral Azacitidine (CC-486) compared to Investigator’s Choice Therapy in Patient with Relapsed or Refractory Angioimmunoblastic T cell Lymphoma

Status: open

Start: September 2019 (in Austria)

Coordinating Investigator: Assoc.-Prof. Priv.-Doz. DDr. Philipp Staber

EudraCT Number: 2017-003909-17

ClinicalTrialsID: NCT03593018

Number of patients: 86 (international)

Sponsor: LYSARC; AGMT Sponsor representative in Austria

This study evaluates the efficacy of Oral azacitidine versus single-agent Investigator’s Choice Therapy in patients with Relapsed or Refractory Angioimmunoblastic T-cell Lymphoma.

Compared to B-cell Non-Hodgin Lymphoma (NHL), Angioimmunoblastic T-cell Lymphoma (AITL) is more resistant to conventional chemotherapy and is generally associated with an inferior outcome. In case of relapsed of refractory disease, survival durations are in the range of only a few months.

Several agents have been evaluated in this setting in recent years: romidepsin, bendamustine or belinostat. The response rate with these agents rarely exceeds 30% and responses are usually of limited duration.

Azacitidine is a nucleoside metabolic inhibitor indicated for the treatment of patients with various myelodysplastic syndrome (MDS) subtypes. In this case, azacitidine significantly increase the survival time compared to standard of care option. This response to azacitidine could be correlated to the existence of recurrent mutations and those mutations have also been described in AITL.

The present protocol will use Azacitidine according to the same schedule than in MDS that is continuous treatment until progression or unacceptable toxicity.

Experimental: Oral Azacitidine
Oral azacitidine 300mg during 14 first days of 28-days cycle for European (EU) patients, Oral azacitidine 200mg during 14 first days of 28-days cycle for Asian patients (Treatment until progression, patient decision or toxicity)

Active Comparator: Investigator’s choice therapy
Bendamustine 120mg/m² on days 1 and 2 of a 21-days cycle (during 6 cycles) or Gemcitabine 1200mg/m² on days 1, 8 and 15 of a 28-days cycle (during 6 cycles)