Health TrialsbyHealthPanel

Pembrolizumab, Ibrutinib and Rituximab in PCNSL

ConditionsPrimary Central Nervous System LymphomaRecurrent CancerRefractory CancerRelapsed Cancer
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorDana-Farber Cancer Institute

About this trial

This research study is evaluating a combination therapy of 3 drugs as possible treatments for recurrent primary central nervous system lymphoma (PCNSL).

The three drugs being used in the study are:

* Pembrolizumab (MK3475) * Ibrutinib * Rituximab (or biosimilar)

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Participant must be able to understand and willing to sign a written informed consent document.

Participant must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal subject care.

Participant must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the study.

Participant must be at least 18 years old on day of signing informed consent.

Disqualifiers

Patients who cannot undergo MRI brain

Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40,CD137)

Previously progressed on ibrutinib or other BTK inhibitor use (patient who have previously received BTK inhibitor but not progressed while on it are allowed)

Patients with > Grade 2 intracranial hemorrhage

Trial design

Design model

Single group

Treatments tested in this trial

  • Ibrutinib

    Drug

    Capsule, taken by mouth daily

  • Pembrolizumab

    Drug

    Given as an intravenous injection through a vein (IV) every 3 weeks

  • Rituximab

    Drug

    Given as infusion into a vein (intravenous, IV)

Treatment groups

37 Participants
are divided into 1 treatment group
Group A: Pembrolizumab + Ibrutinib + RituximabExperimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

Progression-free survival rate 6 months (PFS6)

The primary endpoint of PFS6 will be estimated as a binomial response proportion. The efficacy analysis population will include all evaluable patients (subjects will be considered evaluable for efficacy as long as they have received at least 75% of the planned doses for the 1st 6 weeks of treatment). Patients missing 6 months progression evaluation (for any reason) will be counted as progressors. For the primary analysis, the proportion of progression free patients at 6 months will be evaluated and 95% exact binomial CI will be provided. The Kaplan-Meier method will be used as a secondary approach to evaluate the PFS6 based on the recorded times to progression for each patient, with patients without progression or lost to follow-up being censored at their last follow-up date.

Time frame
6 months

Secondary outcomes

1

Number of Participants With Treatment-Related Adverse Events CTCAE version 5.0.

All subjects receiving at least 1 dose of study treatment will be evaluated for toxicities. DLT rates will be summarized and 95% exact binomial CI will be reported.

Time frame
24 Months
2

Objective response rate (ORR)

The objective response rate (ORR) is defined as the proportion of patients with a best response of CR or PR. Objective Response Rate will be reported with 95% exact binomial CI. OS, PFS and duration of response endpoints will be evaluated by the Kaplan-Meier method and medians will be provided with 95% pointwise CI based on the log-log transformation. For all time to event analysis, patients without event information will be censored at the time of last available data.

Time frame
24 months
3

Duration of response rate

Duration of response will be defined as the time form initial, complete or partial response to the time of disease progression or death. If a patient does not experience disease progression or death before the end of study, duration of response will be censored at the day of the last tumor assessment. OS, PFS and duration of response endpoints will be evaluated by the Kaplan-Meier method and medians will be provided with 95% pointwise CI based on the log-log transformation. For all time to event analysis, patients without event information will be censored at the time of last available data.

Time frame
24 Months
4

Progression-free survival (PFS) Rate

Progression-free survival (PFS) is defined from start date of study treatment to the date of documented progression or death by any cause, whichever comes first. OS, PFS and duration of response endpoints will be evaluated by the Kaplan-Meier method and medians will be provided with 95% pointwise CI based on the log-log transformation. For all time to event analysis, patients without event information will be censored at the time of last available data.

Time frame
24 Months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Dana-Farber Cancer Institute

Lead sponsor

Merck Sharp & Dohme LLC

Collaborator

Source ClinicalTrials.gov
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