NCT04279938

Brief Summary

Safety run-in (part 1): Relapsed or refractory B-cell Non-Hodgkin lymphoma (NHL) Main study (part 2): Relapsed or refractory diffuse large B-cell lymphoma

Trial Health

30
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Timeline
Completed

Started Sep 2018

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 12, 2018

Completed
8 months until next milestone

Study Start

First participant enrolled

September 1, 2018

Completed
1.5 years until next milestone

First Posted

Study publicly available on registry

February 21, 2020

Completed
9 days until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2020

Completed
10 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2021

Completed
Last Updated

February 21, 2020

Status Verified

February 1, 2020

Enrollment Period

1.5 years

First QC Date

January 12, 2018

Last Update Submit

February 19, 2020

Conditions

Relapsed or Refractory Diffuse Large B-cell Lymphoma

Outcome Measures

Primary Outcomes (1)

  • Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    Part 1 (safety run-in): To assess the safety and tolerability of pembrolizumab in combination with R-tinostamustineand to recommend a safe and tolerated dose of tinostamustinefor use in part 2 in combination with 200mg pembrolizumab and 375mg/m2 rituximab . Part 2 (main study): To assess efficacy of pembrolizumab in combination with R-tinostamustineas determined by best overall response in subjects with relapsed/refractory (r/r) DLBCL.

    2.3 years

Secondary Outcomes (1)

  • Secondary Objectives

    2.3 years

Study Arms (1)

Safety Run in & Main Efficacy Part

OTHER

Part 1 (safety run-in) aims to evaluate the maximum tolerated dose (MTD) of tinostamustinein combination with pembrolizumab (200mg Q3W) and rituximab (375mg/m2 Q3W). The dose of tinostamustineestablished to be safe and tolerable in this combination will be used in part 2 of the trial (main efficacy part). The aim of part 2 is to detect signals of anti-tumour activity and to further assess the safety of this combination treatment in r/r DLBCL. The study has a strong focus on correlative research in order to identify mechanisms of response and resistance to pembrolizumab and the pembrolizumab/R-tinostamustinecombination.

Drug: TinostamustineinDrug: PembrolizumabDrug: Rituximab

Interventions

TinostamustineinDRUG

Tinostamustine80-120mg IV Q3W (dose to be determined in part 1) for 6 cycles

Safety Run in & Main Efficacy Part
PembrolizumabDRUG

Pembrolizumab 200mg IV Q3W until disease progression or unacceptable toxicities (max. 2 years)

Safety Run in & Main Efficacy Part
RituximabDRUG

Rituximab 375 mg/m2 IV Q3W for 6 cycles

Safety Run in & Main Efficacy Part

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Histologically proven CD20+ DLBCL (including transformed lymphoma)
  • Previous treatment with at least 1 line of standard therapy
  • Age 18 or over
  • ECOG performance status 0/1 Measurable disease on cross-sectional imaging that is at least 1.5 cm in the longest diameter and measureable in two perpendicular dimensions
  • Adequate organ function
  • Resolution of prior systemic therapy related non-haematological AEs to grade (G) ≤ 1. Participants with ≤ G 2 neuropathy may be eligible.
  • Consent to provide fresh tumour tissue during screening and treatment

You may not qualify if:

  • CNS or leptomeningeal involvement
  • Autologous stem cell transplant (ASCT) within 12 weeks or other anticancer treatment within 3 weeks of commencing therapy
  • Prior allogeneic transplant
  • Known HIV, or active Hepatitis B/C infection
  • Active systemic autoimmune disease
  • No previous therapy with agents targeting immune checkpoint proteins

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

The Royal Marsden NHS Foundation Trust

Sutton, Surrey, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

RecurrenceLymphoma, Large B-Cell, Diffuse

Interventions

pembrolizumabRituximab

Condition Hierarchy (Ancestors)

Disease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsLymphoma, B-CellLymphoma, Non-HodgkinLymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Professor David Cunningham

    The Royal Marsden Hospital NHS Foundation Trust

    STUDY CHAIR
0

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 12, 2018

First Posted

February 21, 2020

Study Start

September 1, 2018

Primary Completion

March 1, 2020

Study Completion

January 1, 2021

Last Updated

February 21, 2020

Record last verified: 2020-02

Data Sharing

IPD Sharing
Will not share

Locations

GB(1)