Combination of Pembrolizumab With TGR-1202 in Patients With Relapsed/Refractory CLL and B-cell NHL
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|ClinicalTrials.gov Identifier: NCT03283137|
Recruitment Status : Recruiting
First Posted : September 14, 2017
Last Update Posted : April 17, 2018
|Condition or disease||Intervention/treatment||Phase|
|CLL B-cell Non Hodgkin Lymphoma||Drug: TGR-1202 Drug: Pembrolizumab||Phase 1|
Of note, TGR-1202 has not been associated with treatment related pneumonitis, transaminitis, colitis, PCP-infection nor CMV-reactivation which distinguishes TGR-1202 from idelalisib's toxicity profile.
Once the maximum tolerated dose has been safely reached the study will open an expansion cohort to enroll 18 patients with a patient group in which a clinical signal is detected. Another 7 patients (up to a total of 25 patients in the expansion cohort) may be enrolled after an interim analysis. The duration of therapy will be 2 cycles of TGR-1202 followed by 8 cycles with pembrolizumab and TGR-1202. Thereafter patient will continue on TGR-1202 at the MTD until disease progression. Subjects who experience disease progression while on TGR-1202 maintenance may be eligible for re-treatment with pembrolizumab for up to 6 cycles at the discretion of the Local Investigator if the patient experienced at least disease stabilization during the initial treatment with pembrolizumab, the subject meets the safety parameters listed in the inclusion/exclusion criteria, and the trial is still open. Subjects will resume therapy at the same dose and schedule at the time of initial discontinuation. If safety and feasibility of the combination is confirmed in this dose expansion cohort, a randomized phase II trial comparing TGR-1202 with pembrolizumab versus TGR-1202 could be considered in a larger patient population, possibly within the cooperative group setting for patients with relapsed/refractory B-cell NHL and CLL
The primary objective of the dose expansion cohort will be CR rate. Secondary endpoints will include safety and feasibility, PFS, OS and clinical response (SD, PR, PD).
Patients will be monitored for disease response, adverse events and survival for a minimum of 2 years following enrollment. During and after treatment, patients will be evaluated for toxicities, particularly immunologic adverse events including pneumonitis, autoimmune colitis, dermatitisetc. Peripheral blood, lymph node and bone marrow samples will be collected before and during the treatment course for the correlative studies outlined below. Complete blood counts and differential counts with a complete metabolic panel will be obtained at the time intervals. If the patients are confirmed to have disease progression or intolerable toxicities the patients will be offered alternative treatment at the physicians' discretion. All of the patients will be followed for survival. All patients will receive HSV prophylaxis with acyclovir 400mg po bid or per institutional standards.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||36 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I, Open-label, Dose-escalation Study to Assess the Safety, Tolerability and Efficacy of the Combination of Pembrolizumab With TGR-1202 in Patients With Relapsed/Refractory CLL and B-Cell Non-Hodgkin Lymphoma (NHL)|
|Actual Study Start Date :||January 23, 2018|
|Estimated Primary Completion Date :||December 2020|
|Estimated Study Completion Date :||December 2020|
Experimental: TGR-1202 and pembrolizumab
All patients will receive TGR-1202 and pembrolizumab. Patients will start receiving TGR-1202 daily for 6 weeks (2 cycles). Pembrolizumab will be given every 3 weeks for 8 cycles. If the daily dose of TGR-1202 (dose level 1) is tolerated in the first cohort the dose will be increased which is the only and final dose escalation. If TGR-1202 is not tolerated the dose will be decreased.
TGR-1202 will be given at a dose of 600mg (dose level 1) or 800mg (dose level 2). If the dose of 600mg is tolerated in the first cohort, then the dose will be increased to 800mg which is the only and final dose escalation. If the dose of 600mg is not tolerated, then the dose will be decreased to 400mg daily.
Other Name: umbralisib
Pembrolizumab will be given at 200 mg every 3 weeks. The dose will not be adjusted throughout the course of the study.
Other Name: Keytruda
- Number of patients with adverse events [ Time Frame: Up to 3 years. ]To determine the maximally tolerated dose of TGR-1202 in combination with pembrolizumab by finding the number of patients with adverse events. This information will be used to determine the recommended phase II dose for this combination for patients with relapsed/refractory CLL/SLL and B-cell NHL.
- proportion of patients with complete remission (CR) [ Time Frame: Up to 3 years ]The proportion of subjects who achieve a confirmed CR by the the international workshop on CLL (iwCLL) and the Lugano Response Criteria for Non-Hodgkin's Lymphoma.
- duration of response (DOR) [ Time Frame: Up to 3 years ]The interval from the first documentation of confirmed CR or PR (by IRC) to the first documentation of definitive disease progression or death from any cause. Definitive disease progression is CLL progression based on standard criteria excluding lymphocytosis alone.
- progression free survival (PFS) rate [ Time Frame: From the start of treatment until the date of first documented progression or date of death from any cause, whichever comes first, up to 100 months ]The interval from the first dose of study drug to the first documentation of definitive disease progression or death from any cause.
- MRD negativity rate [ Time Frame: Up to 3 years ]The proportion of subjects with MRD <10-4, assessed by flow cytometry in bone marrow.
- nodal response rate [ Time Frame: Up to 3 years ]The proportion of subjects who achieve a 50% decrease from baseline in the sum of the products of the greatest perpendicular diameters (SPD) of index lesions.
- overall survival (OS) rate [ Time Frame: From the start of treatment until the date of death from any cause, whichever comes first, up to 100 months ]The interval from the start of study treatment to death from any cause.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03283137
|Contact: Howard Weineremail@example.com|
|United States, Illinois|
|University of Chicago||Recruiting|
|Chicago, Illinois, United States, 60637|
|Contact: Michael Thirman, MD firstname.lastname@example.org|
|Contact: Howard Weiner 7737022084 email@example.com|
|Principal Investigator:||Michael Thirman, MD||University of Chicago|