NCT05820841

Brief Summary

The goal of this clinical trial is to study the addition of Acalabrutinib to standard R-miniCHOP in older adults with DLBCL. The main question it aims to answer is whether progression free survival kann be prolonged with the addition of Acalabrutinib. Participants will be randomised to receive either R-miniCHOP alone or R-miniCHOP with Acalabrutinib.

Trial Health

77
On Track

Trial Health Score

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

Enrollment
330

participants targeted

Target at P50-P75 for phase_3

Timeline
31mo left

Started Jun 2023

Longer than P75 for phase_3

Geographic Reach
1 country

17 active sites

Status
recruiting

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

Study Progress53%
Jun 2023Dec 2028

First Submitted

Initial submission to the registry

March 8, 2023

Completed
1 month until next milestone

First Posted

Study publicly available on registry

April 20, 2023

Completed
2 months until next milestone

Study Start

First participant enrolled

June 7, 2023

Completed
4.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2028

Expected
8 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2028

Last Updated

August 31, 2023

Status Verified

August 1, 2023

Enrollment Period

4.8 years

First QC Date

March 8, 2023

Last Update Submit

August 30, 2023

Conditions

Large B-cell LymphomaDiffuse Large B Cell Lymphoma

Keywords

Diffuse large B cell lymphomaOlder adultsGeriatricLarge B cell lymphomaAggressive B cell lymphomaAcalabrutinibR-miniCHOPR-mini-CHOPBTK inhibitor

Outcome Measures

Primary Outcomes (1)

  • Progression-free survival (PFS) investigator assessed

    PFS, defined by the time between the day of randomization until one of the following events occurs, whichever comes first: Disease progression (PD), relapse after complete remission (CR) or death due to any cause, as per Lugano Classification of 2014. Patients who have not experienced an event at the time of analysis will be censored at the most recent date of disease assessment.

    Up to 5 years

Secondary Outcomes (16)

  • Overall survival (OS)

    Up to 5 years

  • PFS based on blinded independent central review (BICR)

    Up to 5 years

  • Event-free survival (EFS)

    Up to 5 years

  • PFS according to Cell of Origin as per immunohistochemistry

    Up to 5 years

  • OS according to Cell of Origin as per immunohistochemistry

    Up to 5 years

  • +11 more secondary outcomes

Study Arms (2)

Standard arm

ACTIVE COMPARATOR

6x R-miniCHOP + 2x Rituximab.

Drug: R-miniCHOP

Experimental arm

EXPERIMENTAL

6x R-miniCHOP + 2x Rituximab + Acalabrutinib.

Drug: R-miniCHOP + Acalabrutinib

Interventions

R-miniCHOP + AcalabrutinibDRUG

* Rituximab i.v.: 375 mg/m2 (D0) * Cyclophosphamide i.v.: 400 mg/m² (D1) * Doxorubicin i.v.: 25 mg/m² (D1) * Vincristine i.v.: 1 mg (D1) * Prednisolone p.o.: 40 mg/m² (D1 to D5) * Acalabrutinib 100 mg p.o. twice daily starting from D1 of first R-miniCHOP cycle continuously to D21 of cycle 8. Cycles repeated every 3 weeks

Experimental arm
R-miniCHOPDRUG

* Rituximab i.v.: 375 mg/m2 (D0) * Cyclophosphamide i.v.: 400 mg/m² (D1) * Doxorubicin i.v.: 25 mg/m² (D1) * Vincristine i.v.: 1 mg (D1) * Prednisolone p.o.: 40 mg/m² (D1 to D5). Cycles repeated every 3 weeks

Standard arm

Eligibility Criteria

Age61 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Informed consent
  • Ability to understand the purpose and risks of the study and capable of giving signed informed consent which includes:
  • Compliance with the requirements and restrictions listed in the informed consent form (ICF).
  • Authorization to use protected health information/data \[in accordance with the General Data Protection Regulation (GDPR)\].
  • Provision of signed and dated, written ICF prior to any mandatory study specific procedures, sampling, and analyses
  • Willing and able to participate in all required evaluations and procedures in this study protocol, including swallowing capsules and tablets without difficulty.
  • Age/Sex
  • Men and women \>80 years of age or \>60 up to 80 years of age and ineligible for full dose R-CHOP according to investigator assessment\*.
  • We recommend classifying patients aged 61-80 as full-dose R-CHOP ineligible if they fulfill one of the following criteria: ADL \<5, IADL \<6, CIRS-G ≥1 score = 3, or \> 8 score = 2.
  • Male patients who are sexually active with women of childbearing potential (definitions see section 17.8) must agree to use highly effective forms of contraception with the addition of a barrier method (condom) during the study (see section 17.8.1) as well as to the restrictions mentioned in section 9.13.
  • Female patients of childbearing potential (definitions see 17.8) who are sexually active must agree to use highly effective forms of contraception while on the study as well as to the restrictions mentioned in section 9.13.
  • Disease characteristics
  • Histologically proven, previously untreated CD20+ diffuse large B-cell lymphoma (DLBCL) according to the 2017 WHO classification including:
  • diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS)
  • primary cutaneous DLBCL leg type
  • +19 more criteria

You may not qualify if:

  • Medical conditions
  • Evidence of disease (such as severe or uncontrolled systemic diseases, including uncontrolled hypertension and renal transplant) that, in the investigator's opinion, make it undesirable for the patient to participate in the study or that would jeopardize compliance with the protocol \[e.g. a single score of 4 on one single category on the CIRS-G-Score (but not a cumulative score of 4)\].
  • Significant cardiovascular disease such as symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of randomization or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or LVEF \< 40%. Patients with controlled, asymptomatic atrial fibrillation are allowed to enroll on study.
  • Severe pulmonary dysfunction (CTCAE grade 3 or 4) unless associated with lymphoma.
  • Severe psychiatric or neurologic disease that, in the investigator's opinion, make it undesirable for the patient to participate in the study or that would jeopardize compliance with the protocol.
  • Persistent neuropathy CTCAE grade 3 or 4.
  • Refractory nausea and vomiting, inability to swallow acalabrutinib, or malabsorption syndrome; chronic severe gastrointestinal disease, gastric restrictions, or bariatric surgery such as gastric bypass; partial or complete bowel obstruction, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of study treatment.
  • History of prior malignancy that could affect compliance with the protocol or interpretation of results, except for the following:
  • Curatively treated localised basal cell carcinoma or localised squamous cell carcinoma of the skin or carcinoma in situ of the cervix or carcinoma in situ / low risk carcinoma of the prostate requiring only observation, as well as untreated low grade lymphoma except chronic lymphocytic leukemia.
  • Other cancers not specified above that have been curatively treated by surgery and/or radiation therapy from which patient is disease-free for ≥2 years (≥5 years for those treated with chemotherapy) without further treatment or which are not expected to limit survival to \< 2 years.
  • Received a live virus vaccination within 28 days of randomization.
  • Known history of infection with HIV.
  • Any active significant infection (e.g., bacterial, viral or fungal) as assessed by the investigator.
  • History of or ongoing confirmed progressive multifocal leukoencephalopathy (PML).
  • Serologic status reflecting active hepatitis B or C infection.
  • +17 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (17)

Saarland University Medical Center

Homburg, Saarland, 66421, Germany

RECRUITING

MVZ am Klinikum Aschaffenburg

Aschaffenburg, Germany

NOT YET RECRUITING

Helios Klinikum Emil von Behring

Berlin, Germany

RECRUITING

Onkologische Schwerpunktpraxis Kurfürstendamm

Berlin, Germany

NOT YET RECRUITING

Gemeinschaftspraxis Mohm/Prange-Krex

Dresden, Germany

NOT YET RECRUITING

Universitätsklinikum Gießen und Marburg, Standort Gießen

Giessen, Germany

RECRUITING

Universitätsmedizin Greifswald

Greifswald, Germany

RECRUITING

Universitätsmedizin Halle (Saale)

Halle, Germany

RECRUITING

Städtisches Klinikum Karlsruhe

Karlsruhe, Germany

RECRUITING

Johannes Wesling Klinikum

Minden, Germany

NOT YET RECRUITING

Rheinland Klinikum-Lukaskrankenhaus Neuss

Neuss, Germany

NOT YET RECRUITING

Brüderkrankenhaus St. Josef

Paderborn, Germany

NOT YET RECRUITING

CaritasKlinikum Saarbrücken St. Theresia

Saarbrücken, Germany

RECRUITING

Klinikum Mutterhaus der Borromäerinnen

Trier, Germany

RECRUITING

Krankenhaus der Barmherzigen Brüder Trier

Trier, Germany

NOT YET RECRUITING

Bundeswehrkrankenhaus Ulm

Ulm, Germany

NOT YET RECRUITING

Universitätsklinikum Ulm

Ulm, Germany

RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

acalabrutinib

Condition Hierarchy (Ancestors)

Lymphoma, B-CellLymphoma, Non-HodgkinLymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Study Officials

  • Konstantinos Christofyllakis, MD MSc

    Saarland University Medical Center

    PRINCIPAL INVESTIGATOR

  • Moritz Bewarder, MD, PD

    Saarland University Medical Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 8, 2023

First Posted

April 20, 2023

Study Start

June 7, 2023

Primary Completion (Estimated)

April 1, 2028

Study Completion (Estimated)

December 1, 2028

Last Updated

August 31, 2023

Record last verified: 2023-08

Locations

DE(17)