Clinical Trial: Entospletinib and Obinutuzumab in Treating Patients With Relapsed Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or Non-Hodgkin Lymphoma

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: A Phase I/II Study of Syk Inhibitor Entospletinib (GS-9973) in Combination With Obinutuzumab in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) and

Brief Summary: This phase I/II trial studies the side effect and best dose of entospletinib when giving together with obinutuzumab and to see how well they work in treating patients with chronic lymphocytic leukemia, small lymphocytic lymphoma, or non-Hodgkin lymphoma that has come back. Entospletinib may stop the growth of cancer cells by blocking some of the enzymes need for cell growth. Monoclonal antibodies, such as obinutuzumab, may interfere with the ability of cancer cells to grow and spread. Giving entospletinib and obinutuzumab together may work better in treating patients with chronic lymphocytic leukemia, small lymphocytic lymphoma, or non-Hodgkin lymphoma.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To evaluate the safety and tolerability of entospletinib administered in combination with obinutuzumab in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and non-Hodgkin lymphoma (NHL), and identify the dose for phase 2 expansion. (Phase I) II. To evaluate the efficacy of entospletinib in combination with obinutuzumab in patients with relapsed or refractory CLL/SLL, as measured by complete response (CR) rate. (Phase II)

SECONDARY OBJECTIVES:

I. Objective response rate (ORR, defined as complete remission, complete response with incomplete marrow recovery, partial remission and nodular partial response). (Phase II) II. Event free survival defined as the interval between the date of first study treatment and the date of objective signs of disease recurrence, subsequent anti-leukemic therapy, or death, whichever is first reported. (Phase II) III. Safety and tolerability of entospletinib in combination with obinutuzumab by adverse events (AEs). (Phase II)

TERTIARY OBJECTIVES:

I. Peripheral blood B-cell depletion and recovery. II. Preliminary assessment of the predictive value of minimal residual disease (MRD).

III. Pharmacodynamics effects of in vivo administration of entospletinib on NFkappaB activation and expression of anti-apoptotic proteins in CLL cells.

IV. Association of established biomarkers (chromosomal abnormalities, immunoglobulin heavy chain [IGHV] mutational status, p53 mutational status) with response (ORR and event-free survival [EFS]) to entospletinib (ENTO) in combination with obinutuzumab i
Sponsor: OHSU Knight Cancer Institute

Current Primary Outcome:

  • CR defined as the proportion of subjects who achieve CR (Phase II) [ Time Frame: Up to 5 years ]
    The CR will be computed and presented together will the exact 95% confidence interval (CI), using the method of Clopper and Pearson. A null hypothesis of a 20% CR will be rejected if at least 7 of 17 patients achieve a CR and a treatment arm will not be considered further if this threshold is not reached.
  • MTD and/or a recommended phase II dose as measured by the incidence of dose limiting toxicities assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (Phase I) [ Time Frame: Up to 28 days ]
    All adverse events will be tabulated and summarized by major organ category, grade, anticipation, and drug attribution. Severe adverse event specific incidence and exact 95% confidence interval will be provided where appropriate.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Event free survival (Phase II) [ Time Frame: The interval between the date of first study treatment and the date of objective signs of disease recurrence, subsequent anti leukemic therapy, or death, whichever is first reported, assessed up to 5 years ]
    Will be summarized descriptively using the Kaplan-Meier estimate.
  • Incidence of adverse events assessed by NCI CTCAE version 4.03 [ Time Frame: Up to 5 years ]
    Will be summarized for the safety population separately for phase 1 and phase 2 portions by dose level. All AEs will be coded by system organ class, MedDRA preferred term, and severity grade using NCI CTCAE (version 4.03).
  • ORR (Phase II) [ Time Frame: Up to 5 years ]
    Will be summarized with 95% confidence intervals.


Original Secondary Outcome: Same as current

Information By: OHSU Knight Cancer Institute

Dates:
Date Received: January 3, 2017
Date Started: June 1, 2017
Date Completion: February 28, 2024
Last Updated: May 18, 2017
Last Verified: May 2017