NCT03191981

Pembrolizumab Cyclophosphamide and Lenalidomide for Patients With Relapsed Multiple Myeloma

A Phase I/II Trial Investigating the Combination of Pembrolizumab (Keytruda) With Cyclophosphamide and Lenalidomide for Patients With Relapsed Multiple Myeloma

• Status: Withdrawn
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: University of Leeds · Academic / Other
• Sex: All
• Age: 18 Years – 99 Years
• Healthy volunteers: Not accepted

Summary

This is a multi-centre phase I/II trial with an initial dose finding phase for cyclophosphamide and lenalidomide combined with fixed dose pembrolizumab for patients with relapsed or relapsed / refractory multiple myeloma (MM) that have had at least 1 prior line of therapy

Detailed description

This is a multi-centre phase I/II trial with an initial dose finding phase for cyclophosphamide and lenalidomide combined with fixed dose pembrolizumab for patients with relapsed or relapsed / refractory MM that have had at least one prior line of therapy. As this combination has not been given before, participants will be registered initially into a dose finding phase where dose limiting toxicities (DLTs) will be monitored during the first cycle in order to confirm the recommended dose schedule (RD) of cyclophosphamide with lenalidomide and fixed dose pembrolizumab. A modified toxicity probability interval (mTPI) approach has been taken for dose finding, to determine a safe dose schedule defined as the probability of dose limiting toxicity below an acceptable rate of 34%. Once a RD is identified an expansion phase is planned to estimate the activity profile of the Key-CR combination at the RD. The trial will start at the highest dose schedule . Cohorts of 3 evaluable participants will sequentially be recruited to the trial until the RD has been identified or the trial stopped due to excessive toxicity at dose schedule -1. The dose schedule to be given to a subsequent cohort will be evaluated after all participants have been followed up for one cycle or experienced a DLT. The Safety Review Committee (SRC) will be presented with a complete safety report in addition to a set of predetermined dosing decisions, such that all relevant information available may be considered before deciding upon the next dose schedule to be allocated. The mTPI is an adaptive Bayesian design specifying that the parameter for the probability that a patient experiences a DLT during the first cycle follows a separate distribution for each dose level. Each DLT probability is believed to be equally likely to take any value between 0 and 1 before any data is collected this represents a non-informative or flat prior. The posterior distribution from which escalation decisions are made is constructed by updating the prior distribution with observed data and represents our updated beliefs about the parameter after having seen the data. The decision to remain at the current dose schedule (S), escalate (E), or de-escalate (D) from the posterior distribution is determined by probability theory and two clinical criteria; the minimum DLT rate that if true would warrant escalation and the maximum DLT rate that if true would warrant dose de-escalation. The clinical interval is specified to be (0.2, 0.34) in this setting. Below 0.2 would represent under-dosing and warrant escalation, above 0.34, over-dosing and de-escalation and in the interval proper dosing and the decision to remain at the current dose level. Participants will be registered to a dose schedule in cohorts of 3 evaluable participants and a decision regarding expansion or dose (de)escalation will be made once all patients have been followed up for the full DLT observation period (see below). A minimum of 6 participants must be evaluated at a dose schedule for the dose schedule to be considered the RD. If dose schedule -1 or 0 meet the RD criterion but the dose schedule above has not been excluded, a further cohort of participants may be treated at the dose schedule above at discretion of the SRC. If dose schedule -1 is found to be unsafe the trial will terminate early without opening the expansion phase. The SRC may consider increasing the size of cohorts after 12 evaluable participants have been treated at a dose schedule without identifying the RD. Once the RD has been identified the trial will move into the expansion phase. It is essential that the data for each participant is returned in a timely manner to allow the participants to be monitored for safety and dose limiting toxicities that could affect the safety of other participants. Data must be returned on time to allow a timely review of the trial by the Safety Review Committee to prevent a hold up in progressing the trial to the next phase or dose level, or to allow it to be stopped quickly in the event of an unforeseen issue occurring. Dose Schedules - 28 days schedule Dose schedule 1 (starting dose) Pembrolizumab 200mg every 3 weeks, cyclophosphamide 500mg days 1\&8, lenalidomide 25mg days 1-21 Dose schedule 0 Pembrolizumab 200mg every 3 weeks, cyclophosphamide 500mg day 1, lenalidomide 25mg days 1-21 Dose schedule -1 Pembrolizumab 200mg every 3 weeks, cyclophosphamide 500mg day 1, lenalidomide 15mg days 1-21

Conditions

• Myeloma Multiple

Interventions

Type	Name	Description
DRUG	Cyclophosphamide	Treatment for all patients will be with cyclophosphamide, lenalidomide and pembrolizumab at fixed doses.
DRUG	Lenalidomide	Treatment for all patients will be with cyclophosphamide, lenalidomide and pembrolizumab at fixed doses.
DRUG	Pembrolizumab	Treatment for all patients will be with cyclophosphamide, lenalidomide and pembrolizumab at fixed doses.

Timeline

• Start date: 2017-08-01
• Primary completion: 2017-08-01
• Completion: 2017-08-01
• First posted: 2017-06-19
• Last updated: 2017-08-24

Locations

4 sites across 1 country: United Kingdom