NCT02752204

An Evaluation AZD2014 Alone and in Combination With Rituximab in Relapsed/Refractory Diffuse Large B Cell Lymphoma

Torch: A Phase II Study to Determine the Safety and Efficacy of the Dual mTORC Inhibitor AZD2014 and to Investigate Additional Toxicities in Combination With Rituximab in Relapsed/Refractory Diffuse Large B Cell Lymphoma (DLBCL)

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 36 (actual)
• Sponsor: University of Birmingham · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The aim of this clinical trial is to see if the drug called AZD2014 is effective and safe to use to treat patients with relapsed or refractory Diffuse Large BCell Lymphoma (DLBCL). The trial will also be looking at combining the antibody (Rituximab) with the drug AZD2014 in a small number of patients to see if this can be done without increasing the toxicity. 36 patients will be recruited to the trial. 30 will receive AZD2014 alone and the remaining 6 will receive AZD2014 plus rituximab. AZD2014 will be given as a 125mg tablet that is to be taken twice a day for 2 days out of every 7 (i.e. on days 1 and 2 of every week). Rituximab will be given via IV infusion on day 1 of every 28 days (once every 4 weeks) for a maximum of 6 cycles.

Detailed description

This is a prospective, single arm, multicentre, phase II clinical trial utilising a two stage design. Stage one will assess the safety and activity of AZD2014 as a single agent in the treatment of DLBCL in 30 patients. Stage two will assess the additional toxicity of combining AZD2014 with Rituximab in an additional 6 patients. Stage two will be recruited following the full recruitment of stage 1. Stage 2 recruitment will be staggered with 3 patients recruited and their safety data evaluated prior to the recruitment of the remaining 3 patients. Post treatment biopsies will be requested at relapse in patients receiving rituximab to assess for evidence of synergy. Once registered to the study, patients will receive AZD2014 125mg bd on an intermittent schedule of 2 days of treatment followed by 5 days with no treatment. Treatment would be on days 1, 2, 8, 9, 15, 16, 22 and 23 of each course 28 days in duration. Treatment is on-going until progression or withdrawal due to toxicity or patient's choice. For the second stage of the trial, rituximab 375mg/m2 will also be administered intravenously on day 1 of the 28 day cycle for a total of 6 cycles in combination with AZD2014. All patients will be followed for a minimum of 1 year up until disease progression or death. For patients still on AZD2014 treatment after 1 year (no progression) treatment should still be reviewed at least 3 monthly. Safety, progression and survival data will be collected every 3 months. Assessments should be as per local practice with a CT scan conducted every 3/4 months. At progression, patients will then be followed up annually for survival data. Tissue, saliva and blood samples will be collected during treatment to determine the activity of AZD2014 on downstream targets, and correlating with response. This will include biopsy tissue from the pre-treatment sample, any biopsy performed on treatment and at relapse post-AZD2014 should this occur

Conditions

• Diffuse Large B-Cell Lymphoma

Interventions

Type	Name	Description
DRUG	AZD 2014	AZD2014 125mg BD - 2 days on 5 days off in a 28 day cycle
DRUG	Rituximab	Rituximab 375mg/m2 will be administered intravenously on day 1 of a 28 day cycle for a total of 6 cycles.

Timeline

• Start date: 2015-10-01
• Primary completion: 2017-09-07
• Completion: 2020-02-06
• First posted: 2016-04-26
• Last updated: 2020-11-05

Locations

9 sites across 1 country: United Kingdom