ENRICH - Randomised, open label study of Rituximab/Ibrutinib vs Rituximab/Chemotherapy in older patients with untreated mantle cell lymphoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Skane, University Hospitals Plymouth NHS Trust

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

6 Dec 2017 → ongoing

Decision date (initial)

2024-09-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-514275-18-00

EudraCT number

2015-000832-13

ISRCTN

ISRCTN11038174

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacogenomic, Efficacy, Safety

To assess whether IR is superior to R-Chemo in terms of progression-free survival (PFS)

Secondary objectives 5

1. To evaluate and compare for each treatment group: Overall survival (OS)
2. To evaluate and compare for each treatment group: Disease response as guided by Cheson 1999
3. To evaluate and compare for each treatment group: Safety and toxicity
4. To evaluate and compare for each treatment group: Quality of life measured by the EORTC QLQ-C30 at baseline, during treatment and at the end of maintenance
5. To evaluate and compare for each treatment group: Time to next MCL treatment

Conditions and MedDRA coding

Mantle Cell Lymphoma (MCL)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Male/female patients 60 years and over
2. Pathologically confirmed MCL, with documentation of monoclonal B cells that have a chromosome translocation t(11;14)(q13;q32) and/or overexpress cyclin D1
3. Stage II-IV disease, measurable (>1.5cm) by imaging and requiring treatment in the opinion of the treating clinician
4. No previous treatment for MCL (other than localised radiotherapy or 7 day pulse of steroids for symptom control)
5. Willingness and ability to take Pneumocystis jiroveci Pneumonia prophylaxis
6. Performance status ECOG 0-2
7. Absolute neutrophil count >1.0x10^9/L and platelets >100x10^9/L independent of growth factor support or unless related to Lymphoma
8. AST and/or ALT <3xULN
9. Total bilirubin ≤1.5xULN unless bilirubin rise is due to Gilbert’s syndrome or of non-hepatic origin
10. Calculated creatinine clearance >30mL/min
11. Cardiac function sufficient to tolerate either Rituximab-CHOP or Rituximab-Bendamustine chemotherapy
12. Able to give voluntary written informed consent

Exclusion criteria 11

1. Patients considered fit enough to undergo autologous or allogeneic stem cell transplant as treatment for MCL
2. CNS involvement of MCL
3. Known serological positivity for HBV, HCV, HIV
4. Vaccinated with live vaccines within four weeks prior to Day 1 of Cycle 1
5. Major surgery within 2 weeks prior to Day 1 of Cycle 1
6. Diagnosed with or treated for any other malignancy other than MCL within 2 years prior to Day 1 of Cycle 1 (except BCC, SCC or any in situ malignancy)
7. Active systemic infection requiring treatment
8. Serious medical or psychiatric illness likely to interfere with participation in this clinical study
9. Concurrent treatment with another investigational agent
10. Male participants with female partners of childbearing potential who are unwilling to use appropriate contraception methods whilst on study treatment
11. Women who are pregnant or breastfeeding

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is progression-free survival (PFS). This is defined as the interval from the date of randomisation to the earlier of the first documentation of disease progression / relapse or death from any cause

Secondary endpoints 5

1. Overall survival will be measured from the date of randomisation to the date of death from any cause
2. Disease response will be assessed in accordance with the International Workshop Standardized Response Criteria for Non-Hodgkin's Lymphoma. Response assessments are to be guided by the Cheson Criteria 1999. Disease response will be formally assessed by CT scans and Bone Marrow biopsies
3. Safety and toxicity - based on adverse events graded by Common Terminology Criteria for Adverse Event reporting (CTCAE) v4.03 and determined by routine clinical assessment
4. Quality of life - EORTC QLQ-C30 will be used to measure participant assessed quality of life
5. Time to next MCL treatment is defined as the interval from the date of randomisation to the start date of next MCL treatment or the date of death from any cause

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Skane

Sponsor organisation

Region Skane

Address

Dockplatsen 26, Malmo S:t Petri Malmo S:t Petri

City

Malmo

Postcode

211 74

Country

Sweden

Scientific contact point

Organisation

Region Skane

Contact name

Mats Jerkeman

Public contact point

Organisation

Region Skane

Contact name

Mats Jerkeman

Third parties 5

University Hospitals Plymouth NHS Trust

Sponsor organisation

University Hospitals Plymouth NHS Trust

Address

Level 7, Derriford Road, Derriford Derriford Road Derriford

City

Plymouth

Postcode

PL6 8DH

Country

United Kingdom

Sponsor responsibilities

Contact point sponsor

Region Skane

Locations

4 EU/EEA countries · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 23 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications