Beschreibung

Rekrutierung beendet

PHASE III RANDOMIZED, OPEN-LABEL, MULTICENTER STUDY EVALUATING EFFICACY AND SAFETY OF MOSUNETUZUMAB IN COMBINATION WITH LENALIDOMIDE IN COMPARISON TO RITUXIMAB IN COMBINATION WITH LENALIDOMIDE IN PATIENTS WITH INDOLENT NON-HODGKIN’S LYMPHOMA AFTER AT LEAST ONE LINE OF SYSTEMIC THERAPY

Studientherapie

M+Len Arm
Mosunetuzumab
Mosunetuzumab will be administered intravenously in a setting with immediate access to
trained critical care personnel and facilities equipped to respond to and manage medical
emergencies. Mosunetuzumab will be administered in a step-up dosing schedule. In
Cycle 1 (21-day cycle), patients will receive 1 mg on Day 1; 2 mg on Day 8; and 30 mg
on Day 15. In Cycle 2-12 (28-day cycle), patients will receive 30 mg on Day 1. See
Figure 2 for dosing regimen.
Initially, mosunetuzumab will be infused over 4 hours (±15 minutes). The infusion may
be slowed or interrupted for patients experiencing infusion-associated symptoms.
Following each mosunetuzumab dose, patients will be observed at least 90 minutes for
fever, chills, rigors, hypotension, nausea, or other signs and symptoms of CRS. In the
absence of infusion-related adverse events, the infusion time of mosunetuzumab in
Cycles 2 and beyond may be reduced to 2 hours (±15 minutes). Patients who receive
the Mosun + Len combination do not require hospitalization. Although, hospitalization is
not mandated, the investigator should actively assess the need for hospitalization, and
patients should be hospitalized whenever clinically indicated. The hospitalization
requirement may be modified based on iDMC recommendation after review of the
emerging safety profile of study treatment.
Lenalidomide
Lenalidomide will be administered PO once daily on Days 1-21 of Cycles 2-12
(28-day cycles) at a dose of 20 mg. See Figure 2 for dosing regimen.
Tocilizumab
Tocilizumab will not be administered to all patients but only to those patients who
experience a CRS event for which tocilizumab is indicated (a rescue IMP). Tocilizumab
will be supplied by the Sponsor. Refer to the local prescribing information for further
instructions regarding recommended storage conditions and packaging configuration.
For patients requiring treatment of CRS, patients will receive tocilizumab by IV infusion.
Patients who weigh
30 kg will receive 8 mg/kg tocilizumab and patients who weigh
<30 kg will receive 12 mg/kg tocilizumab. Doses exceeding 800 mg per infusion are not
recommended. Treatment may be repeated every 8 hours as necessary (for a maximum of four doses).
R+Len Arm
Rituximab
Rituximab must be administered in a clinic or hospital equipped for systemic (IV)
cancer treatment. Full emergency resuscitation facilities should be immediately
available, and patients should be under close observation by the investigator at all
times. In case of infusion-associated adverse events in patients, the signs and
symptoms should be fully resolved before the patient is discharged. 375 mg/m2
rituximab will be administered to patients by IV infusion on D1, 8, 15, and 22 of C1,
followed by administration on D1 of Cycles 3, 5, 7, 9, 11 of 28-day cycles. See Figure 3
for dosing regimen.
Lenalidomide
Lenalidomide will be administered PO once daily on Days 1-21 of Cycles 1-12 (28-day cycles) at a dose of 20 mg. See Figure 3 for dosing regimen.

Studienstatus

Rekrutierungsziel erreicht/keine neuen Patienten

Allgemeine Infos zum Antrag

Herr Joachim Boele
joachim.boele@roche.com

Roche Pharma AG (Unternehmen, 11920)
Hematology Franchise
Emil-Barell-Str. 1
79639 Grenzach-Wyhlen

To evaluate the efficacy of M+Len
compared with R+Len

To evaluate the efficacy of M+Len
compared with R+Len

PATIENTS WITH INDOLENT NON-HODGKIN’S LYMPHOMA AFTER AT LEAST ONE LINE OF SYSTEMIC THERAPY

The purpose of this study is to test the equality of PFS distribution in M+Len versus
R+Len with regard to PFS.
A total of 375 patients is planned for this randomized study, 300 FL patients and a
projection of 75 patients with marginal zone lymphoma (MZL), Assuming a median PFS
of 30 months in the R+Len arm of patients with FL, based on the median PFS reported
in a large Phase IIIb study of R+Len (Andorsky ASCO 2019), and a randomization ratio
of 1:1, and considering an interim analysis for efficacy when 70% of events have been
documented, 122 events are required in patients with FL to detect a between-group
difference of 20 months in median PFS (hazard ratio = 0.6) assuming an exponential
distribution of PFS using a log-rank test with 80% power and a global two-sided type I
error rate of 0.05. Based on the above statistical assumptions and anticipating a
recruitment period of approximately 31 months and a follow-up of 18 months after the
last patient is randomized, approximately 300 FL patients will be randomized in the
global enrollment phase of this study, taking into account an estimated annual dropout
rate of 5%. This corresponds to a minimal detectable PFS HR of 0.7.
In addition, patients with MZL will be randomized in this study and it is expected that
approximately 75 patients will be randomized during the 31 months recruitment period.
Assuming a median PFS of 38 months in the R+Len arm of patients with MZL, based on
the median PFS reported in the Phase IIIb study of R+Len (Andorsky ASCO 2019), it is
expected that the number of events at the time of the primary analysis would be 26 in
the MZL subgroup and the power in the ITT population would be 87% to detect a
between-group difference of 25 months in median PFS (hazard ratio = 0.6).
The clinical cutoff for the primary PFS analysis is expected to be 49 months after the first
patient is enrolled.
The sample size calculation was performed using rpact package in R version 3.5.3.

• Progression free survival (PFS) defined as
the time from randomization to disease
progression or death due to any cause as
determined by the Independent Review
Committee (IRC):
- in the ITT-FL population
- in the ITT population
Note: All radiographic assessments are
according to the Lugano 2014 Response
Criteria

• PFS as determined by the investigator:
- in the ITT-FL population
- in the ITT population
• Complete response (CR) rate in the ITT
population, defined as the proportion of
patients whose best overall response is a
CR on positron emission
tomography/computed tomography
(PET/CT) during the study, as determined
by the:
- IRC
- Investigator
• Objective response rate (ORR) in the ITT
population, defined as the proportion of
patients whose best overall response is a
partial response (PR) or a CR during the
study, as determined by the:
- IRC
- Investigator
• Overall survival in the ITT population,
defined as time from randomization to
death from any cause
• Duration of objective response, defined as
the time from the first occurrence of a
documented objective response (CR or PR)
to disease progression, or death from any
cause, whichever occurs first
• Duration of CR, defined as the time from
the first occurrence of a documented CR to
disease progression, or death from any
cause, whichever occurs first
• Time to deterioration in physical functioning
and fatigue, as measured by:
- The European Organization for
Research and Treatment of Cancer
Quality of LifeCore 30
Questionnaire (EORTC QLQ-C30)
• Time to deterioration in lymphoma
symptoms, as measured by:
- Functional Assessment of Cancer
TherapyLymphoma subscale
(FACT-Lym LymS)

Spezifische Infos zum Antrag

see attached Protocol-Synopsis

see attached Protocol-Synopsis

With consideration of recruitment period of approximately 2.5 years (31 months), and
survival follow up period after last patient in (LPI) of 5 years, the overall duration of the
study is expected to be approximately 7.5 years.
In addition, the Sponsor may decide to terminate the study at any time.
The total length of the study, from screening of the first patient to the end of the study, is
expected to be approximately 8 years.

to be determined

F. Hoffmann-La Roche Ltd

n.a.

n.a.

Ja