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Due to Sponsor reasons.
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This is a Phase 1, non-randomized, open-label, dose-escalation and expansion study, evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical antitumor activity of XL114 administered alone orally to subjects with Non-Hodgkin's Lymphoma (NHL). The objectives of the study also include determining the recommended dose (RD) and/or maximum tolerated dose (MTD) of XL114.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| XL114 Dose-Escalation Cohorts | Experimental | Subjects (Cohort A1-An) will accrue in cohorts of 3-12 subjects in a i3+3 design. |
|
| XL114 Expansion Cohorts | Experimental | The recommended dose from the Dose-Escalation stage, will be used in subjects with activated B-cell-like diffuse large B-cell lymphoma [ABC-DLBCL] (Cohort B), mantle cell lymphoma [MCL] (Cohort C), chronic lymphocytic leukemia [CLL]/small lymphocytic lymphoma [SLL] (Cohort D). Subjects will also be enrolled in a Biomarker cohort (Cohort E). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| XL114 | Drug | Tablets of XL114 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Dose-Escalation Stage: Recommended Dose (RD) and/or Maximum Tolerated Dose (MTD) for XL114 | To determine the RD and/or MTD of XL114 administered orally in subjects with NHL | 4-6 months |
| Cohort-Expansion Stage: Objective Response Rate (ORR) | To evaluate preliminary efficacy of XL114 by estimating the ORR based on lymphoma-specific response criteria as assessed by the Investigator | 4-6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Safety of XL114, as evaluated by Adverse Events (AEs) | To evaluate the safety of XL114 through the evaluation of incidence and severity of treatment emergent nonserious adverse events (AEs) and serious adverse events (SAEs)at each dose level and their relationship to study drug treatment. | 4-6 months |
| Tolerability of XL114, as evaluated by Dose Intensity, Dose Modifications, and Study Discontinuation due to AEs |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Exelixis Clinical Site #3 | Tucson | Arizona | 85719 | United States | ||
| Exelixis Clinical Site #1 |
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Dose-escalation followed by Cohort-expansion in NHL-specific expansion cohorts
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To evaluate the tolerability of XL114 through the evaluation of dose intensity, dose modifications and study treatment discontinuation due to AEs related to XL114. |
| 4-6 months |
| Dose-Escalation Stage: Time to Maximum Plasma Concentration (Tmax) | To evaluate the Tmax of XL114. | 4-6 months |
| Dose-Escalation Stage: Maximum Plasma Concentration (Cmax) | To evaluate the Cmax of XL114. | 4-6 months |
| Dose-Escalation Stage: Area Under the Plasma Concentration-Time Curve Over the Last 24-hour Dosing Interval (AUC 0-24) | To evaluate the AUC 0-24 of XL114. | 4-6 months |
| Dose-Escalation Stage: Terminal Half-Life | To evaluate the terminal half-life of XL114. | 4-6 months |
| Dose-Escalation Stage: Apparent Clearance (CL/F) | To evaluate the CL/F of XL114. | 4-6 months |
| Cohort-Expansion Stage: Antitumor Activity of XL114 (Objective Response Rate [ORR]) | To evaluate the antitumor activity of XL114 as measured by ORR based on lymphoma-specific response criteria as assessed by a Blinded Independent Radiology Committee (BIRC) for selected cohorts. | 4-6 months |
| Cohort-Expansion Stage: Antitumor Activity of XL114 (Duration of Response [DOR]) | To evaluate the antitumor activity of XL114 as measured by DOR based on lymphoma-specific response criteria as assessed by the Investigator or by a Blinded Independent Radiology Committee (BIRC) for selected cohorts. | 4-6 months |
| Cohort-Expansion Stage: Antitumor Activity of XL114 (Progression Free Survival [PFS]) | To evaluate the antitumor activity of XL114 as measured by PFS based on lymphoma-specific response criteria as assessed by the Investigator or by a Blinded Independent Radiology Committee (BIRC) for selected cohorts. | 4-6 months |
| Cohort-Expansion Stage: Overall Survival (OS) of XL114 | To evaluate duration of overall survival (OS) | 4-6 months |
| Indianapolis |
| Indiana |
| 46250 |
| United States |
| Exelixis Clinical #4 | Pittsburgh | Pennsylvania | 15224 | United States |
| Exelixis Clinical Site #2 | Spokane | Washington | 99208 | United States |
| ID | Term |
|---|---|
| D008228 | Lymphoma, Non-Hodgkin |
| D020522 | Lymphoma, Mantle-Cell |
| D015451 | Leukemia, Lymphocytic, Chronic, B-Cell |
| ID | Term |
|---|---|
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D015448 | Leukemia, B-Cell |
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D006402 | Hematologic Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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