Venetoclax in combination with Ibrutinib and Rituximab or conventional chemotherapy (Bendamustine) and Ibrutinib and Rituximab in patients with Mantle Cell Lymphoma.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitatsmedizin der Johannes Gutenberg-Universitat Mainz KöR

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

15 May 2023 → ongoing

Decision date (initial)

2023-11-07

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Janssen Pharmaceutica NV, Germany · AbbVie Inc., Germany

External identifiers

EU CT number

2022-501808-96-00

EudraCT number

2020-002935-30

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

To evaluate efficacy in both treatment arms: Failure-Free Survival (FFS) at 30 from randomization

Secondary objectives 11

1. Failure-free survival (continuous observation)
2. Progression-free survival
3. Complete Remission rate (CR) and overall response rate (ORR: CR, PR) four weeks after the end of induction therapy
4. best response, time to best response, time to first response
5. overall survival
6. Overall survival of patients divided according to the geriatric categories and treatment received
7. Safety: adverse events, tolerability
8. Quality of life during induction and maintenance therapy (assessed using the EORTC QLQ-C30 and the EORTC QLQ-NHL-HG29)
9. Molecular remission after induction and conversion during maintenance (exploratory)
10. Immune reconstitution
11. safety and efficacy in different geriatric categories

Conditions and MedDRA coding

Mantle Cell Lymphoma

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Histologically confirmed diagnosis of MCL according to WHO classification
2. previously untreated stage II-IV (Ann Arbor), previous local therapyi e.g. radiation therapy to single lesion is eligible, a limited pre-phase treatment with steroids for patients at need is allowed (s. treatment)
3. ≥ 60 years and not suitable for autologous SCT
4. At least 1 measurable lesion; in case of bone marrow infiltration only, bone marrow aspiration and biopsy is mandatory for all staging evaluations.
5. ECOG performance status ≤ 2
6. Absolute neutrophil count (ANC) ≥ 1000 cells/μL
7. Platelets ≥75.000 cells/μL
8. Transaminases (AST and ALT) ≤3 x ULN
9. Total bilirubin ≤ 2 x ULN unless other reason known (Gilbert- Meulengracht-Syndrome)
10. Creatinine ≤ 2 mg/dL or eGFR ≥ 50 mL/min
11. Written informed consent form according to ICH/EU GCP and national regulations
12. Sexually active men with female partners of child-bearing potential potential must agree to use highly effective contraceptives

Exclusion criteria 13

1. Major surgery within 4 weeks prior to first dose
2. Patients with unresolved hepatitis B or C infection or known HIV positive infection (mandatory test) Concomitant or previous malignancies within the last 3 years other than basal cell skin cancer, Prostate cancer in remission with PSA within normal range or in situ uterine cervix cancer
3. Requires anticoagulation with warfarin or equivalent vitamin K antagonists (e.g. phenprocoumon)
4. History of stroke or intracranial hemorrhage within 6 months prior to first dose
5. Treatment with strong or moderate CYP3A4/5 inhibitors/inducers within 7 days before first dose and during Venetoclax and Ibrutinib intake
6. Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of Ibrutinib capsules, or put the study outcomes at undue risk
7. Vaccinated with live, attenuated vaccines within 4 weeks prior to first dose
8. Known CNS involvement of MCL
9. Known bleeding disorder (e.g. von Willebrand disease; hemophilia) Serious concomitant disease interfering with a regular therapy according to the study protocol
10. Cardiac (Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification or LVEF below LLN)
11. Patients requiring double platelet inhibition, e.g due to cardiovascular intervention
12. clinically significant pulmonary dysfunction interfering with the conduct of the trial treatment
13. any other significant medical condition interfering with the conduct of the trial treatment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To evaluate efficacy in both treatment arms: Failure-Free Survival (FFS) at 30 months

Secondary endpoints 11

1. Failure-free survival (continuous observation)
2. Progression-free survival
3. Complete Remission rate (CR) and overall response rate (ORR: CR, PR) four weeks after the end of induction therapy
4. best response, time to best response, time to first response
5. overall survival
6. Overall survival of patients divided according to the geriatric categories and treatment received
7. Safety: adverse events, tolerability
8. Quality of life during induction and maintenance therapy (assessed using the EORTC QLQ-C30 and the EORTC QLQ-NHL-HG29)
9. Molecular remission after induction and conversion during maintenance (exploratory)
10. Immune reconstitution, e.g. persistence of anti-Covid19 immunity
11. safety and efficacy in different geriatric categories

Investigational products

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

Test 4

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitatsmedizin der Johannes Gutenberg-Universitat Mainz KöR

Sponsor organisation

Universitatsmedizin der Johannes Gutenberg-Universitat Mainz KöR

Address

Langenbeckstraße 1, Oberstadt Oberstadt

City

Mainz

Postcode

55131

Country

Germany

Scientific contact point

Organisation

Universitatsmedizin der Johannes Gutenberg-Universitat Mainz KöR

Contact name

Sponsor contact point clinical trials

Public contact point

Organisation

Universitatsmedizin der Johannes Gutenberg-Universitat Mainz KöR

Contact name

Sponsor contact point clinical trials

Third parties 2

Locations

2 EU/EEA countries · 41 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 21 files

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

Application history

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