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Clinical picture: NHL (Non Hodgkin Lymphoma)

Trial: HOVON 133 MCL (TRIANGLE)


News
1. Overview
2. Patient eligibility criteria
3. Registration (& randomization) of patients
4. Participating parties
5. Participating sites
6. Instruction videos
7. Download documentation / forms


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News


HO133 News

 

11JAN2017: Start Up meeting for participating HOVON sites was held in Utrecht.

 

18SEP2015: Participants Inquiry is sent to all HOVON sites. Planning is that study will first start in Germany (Q4 2015) after which HOVON will join with 25-30 sites in NL+BE.

 


1. Overview



Summary

Randomized, three-arm, parallel-group, open label, international phase III trial comparing six alternating courses of R-CHOP/R-DHAP (one cycle every 21 days) followed by ASCT versus the combination with ibrutinib in induction and maintenance (2 years) or the experimental arm without ASCT.


Status

planned


Members

Participating Groups: GLSG (sponsor), HOVON, Nordic Lymphoma Group, FIL, SAKK, PLRG, GELTAMO, NCRI



Type of study

Prospective randomized Phase III study


Echelon level

Level D


Echelon level specification

Agreements should be made with a higher echelon site for study parts that your center cannot execute.


Type of monitoring for this study

Study specific


Target number of patients

870


Current number of patients

0


Date of first EC&CA submission

06-Apr-2017


Approved by

EudraCTnr.: 2014-001363-12

Dutch central EC: 28Jul2017
Dutch CA: 18Apr2017

Belgian central EC: 29Jun2017
Belgian CA: 24Apr2017


Study objectives

Primary Objective:
To establish one of three study arms, R-CHOP/R-DHAP followed by ASCT (control arm A), R-CHOP+ibrutinib /R-DHAP followed by ASCT and ibrutinib maintenance (experimental arm A+I), and R-CHOP+ibrutinib /R-DHAP followed by ibrutinib maintenance (experimental arm I) as future standard based on the comparison of the investigator-assessed failure-free survival (FFS).

Secondary Objectives:
To compare the efficacy of the three treatment arms in terms of secondary efficacy endpoints
To determine the safety and tolerability of ibrutinib during induction immuno-chemotherapy and during maintenance and to compare the safety profile of the three treatment arms in terms of secondary toxicity endpoints

Exploratory Objectives:
To compare feasibility of ASCT in arm A+I vs. arm A
To compare minimal residual disease status between the three treatment groups
To determine the impact of ibrutinib during induction immuno-chemotherapy and during maintenance therapy on the minimal residual disease status
To determine the prognostic value of minimal residual disease status
To determine the prognostic value of positron emission tomography with fluorine 18-fluorodeoxyglucose
To determine clinical and biological prognostic and predictive factors
To determine the role of total body irradiation (TBI) in ASCT conditioning


2. Patient eligibility criteria



Inclusion criteria

All patients must meet the following criteria:
Histologically confirmed diagnosis of MCL according to WHO classification
suitable for high-dose treatment including high-dose Ara-C
Stage II-IV (Ann Arbor)
Age ≥ 18 years and ≤ 65 years
Previously untreated MCL
At least 1 measurable lesion; in case of bone marrow infiltration only, bone marrow aspiration and biopsy is mandatory for all staging evaluations.
ECOG/WHO performance status ≤ 2
The following laboratory values at screening (unless related to MCL):
 - Absolute neutrophil count (ANC) ≥ 1000 cells/uL
 - Platelets ≥ 100,000 cells/uL
 - Transaminases (AST and ALT) ≤ 3 x upper limit of normal (ULN)
 - Total bilirubin ≤ 2 x ULN unless due to known Morbus Meulengracht [Gilbert-Meulengracht-Syndrome])
 - Creatinine ≤ 2 mg/dL or calculated creatinine clearance ≥ 50 mL/min
Written informed consent form according to ICH/EU GCP and national regulations
Sexually active men and women of child-bearing potential must agree to use highly effective contraceptives (eg, condoms, implants, injectables, combined oral contraceptives, intrauterine devices, sexual abstinence, or sterilized partner) while on study; this should be maintained for 90 days after the last dose of study drug


Exclusion criteria

Any potential subject who meets any of the following criteria will be excluded from participating in the study.

Major surgery within 4 weeks prior to randomization.
Requires anticoagulation with warfarin or equivalent vitamin K antagonists (eg phenprocoumon).
History of stroke or intracranial hemorrhage within 6 months prior to randomization.
Requires treatment with strong CYP3A4/5 inhibitors.
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.
Vaccinated with live, attenuated vaccines within 4 weeks prior to randomization.
Known CNS involvement of MCL
Clinically significant hypersensitivity (eg, anaphylactic or anaphylactoid reactions to the compound of ibrutinib itself or to the excipients in its formulation)
Known anti-murine antibody (HAMA) reactivity or known hypersensitivity to murine antibodies
Previous lymphoma therapy with radiation, cytostatic drugs, anti-CD20 antibody or interferon except prephase therapy outlined in this trial protocol
Serious concomitant disease interfering with a regular therapy according to the study protocol:
 - 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 )
 - Pulmonary (chronic lung disease with hypoxemia)
 - Endocrinological (severe, not sufficiently controlled diabetes mellitus)
 - Renal insufficiency (unless caused by the lymphoma): creatinine > 2x normal value and/or creatinin clearance < 50 ml/min)
 - Impairment of liver function (unless caused by the lymphoma): transaminases > 3x normal or bilirubin > 2,0 mg/dl unless due to morbus Meulengracht (Gilbert-Meulengracht-Syndrome)
Patients with unresolved hepatitis B or C infection or known HIV positive infection (mandatory test)
Prior organ, bone marrow or peripheral blood stem cell transplantation
Concomitant or previous malignancies within the last 3 years other than basal cell skin cancer or in situ uterine cervix cancer
Pregnancy or lactation
Any psychological, familiar, sociological, or geographical condition potentially hampering compliance with the study protocol and follow up schedule
Subjects not able to give consent
Subjects without legal capacity who are unable to understand the nature, scope, significance and consequences of this clinical trial
Participation in another clinical trial within 30 days before randomization in this study.


3. Registration (& randomization) of patients



Registration

Via eCRF system of sponsor KU Munich:
https://glsg-login.xclinical.net/idp/


4. Participating parties



Principal Investigator(s)

Prof. Dr. M. Dreyling (Klinikum der Universität München)


Coordinating Investigator(s)

Mw. Dr. J.K. Doorduijn (Erasmus MC - Daniel)
Prof. Dr. G.E.G. Verhoef (UZ Gasthuisberg)


Statistician(s)

Ms. Dr. E. Hoster (Klinikum der Universität München)


Monitor - Study Specific

Mw. T. van de Klundert (Erasmus MC - Daniel)
MonitorTeamCTC (Erasmus MC - Daniel)
Mw M. Roelvink-Jansma (Erasmus MC - Daniel)


Other functions

Central Coordinator - MRD - Mw. C. Homburg (Sanquin Research)
Central Coordinator - MRD - Dhr. Dr. V.H.J. van der Velden (Erasmus MC - Centrum)


Trial manager

mw. N. Thuss (n.thuss@erasmusmc.nl)


Central data management

Will be done by sponsor KU München.
eCRF system: https://glsg-login.xclinical.net/idp/


5. Participating sites



Site
Included patients *
NL-Nijmegen-Radboudumc
0

* Please note that if TOP is not used to register patients for a study, the number of patients shown is zero.

6. Instruction videos



7. Download documentation / forms




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