A Randomized Phase 3 Trial of Continuous vs. Intermittent Maintenance Therapy with Zanubrutinib as Upfront Treatment in Older Patients with Mantle Cell Lymphoma (INTERCON)
Categories (click each to see list of all clinical trials associated with that category): Lymphoma/CLL (ONC)
Current Status: Open
Phase: III (Cancer Control)
Principal Investigator: Vose, Julie
Summary
2.1 Primary objective
To compare time to first progression or death (PFS1) with continuous treatment (Arm A) and time to second progression or death (PFS2) with intermittent treatment that is restarted at first progression (Arm B). PFS1 and PFS2 will be defined as follows for patients who achieve complete remission (CR) with induction therapy and are randomized to a maintenance treatment arm:
2.1.1 Continuous treatment Arm A: time from randomization until first progression or death from any cause (PFS1)
2.1.2 Intermittent treatment Arm B: time from randomization until second progression or death from any cause (PFS2)
2.2 Key secondary objective
To compare overall survival between patients who achieve a CR with induction therapy subsequently treated with continuous treatment vs. intermittent treatment as part of maintenance therapy.
2.3 Secondary objectives
2.3.1 To determine overall response rate (ORR) and CR rate to induction therapy with zanubrutinib and rituximab in previously untreated MCL
2.3.2 To determine adverse events during induction and post-induction in each study arm (Arm A and B) by CTCAE 5.0
2.3.3 To determine PFS1, event free survival (EFS) and overall survival (OS) in each study arm (A and B)
2.3.4 To determine the overall response rate (ORR) and complete response rate (CR) after restarting zanubrutinib, following the first progression, in the intermittent treatment arm (Arm B)
2.3.5 To compare burden of symptomatic AEs as assessed by PRO-CTCAE between patients randomized to Arm A versus Arm B.
2.4 Quality of Life Objectives
2.4.1 Primary Objective
- To compare health-related QOL at 12 cycles post-randomization as assessed by the FLYMSI-18 total score between patients randomized to Arm A versus Arm B.
2.4.2 Secondary Objective
- To compare health-related QOL at other time points as assessed by the FLYMSI-18 total score between patients randomized to Arm A versus Arm B.
- To compare burden of symptomatic AEs as assessed by PRO-CTCAE between patients randomized to continuous (Arm A) versus intermittent (Arm B) zanubrutinib treatment.
2.4.3 Exploratory objective
- To compare the geriatric functional and cognitive PRO as assessed by EFLI and Neuro QOL in Arm A versus Arm B.
- To compare cognitive function at various time points as assessed by the Neuro-QOL between patients randomized to continuous (Arm A) versus intermittent (Arm B) zanubrutinib treatment.
2.5 Exploratory objective(s)
2.5.1 To evaluate the completion rate of a lymphoma-specific patient assessment of life survey (PALS) with patient directed questions on life, health, and social determinants of health (SDH) and assess the impact of the survey collected data on outcomes for all enrolled patients (study arms A and B)
2.5.2 To evaluate minimal residual disease (MRD) in those patients who achieve a CR after induction therapy (arms A and B) and how detectable MRD status changes after continued therapy vs. discontinuation of therapy (i.e. arms A vs. B).