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NCT05144347 | Terminated | Non-Hodgkin's Lymphoma (NHL)

Study of XL114 in Subjects With Non-Hodgkin's Lymphoma
Sponsor:

Exelixis

Brief Summary:

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.

Condition or disease

Non-Hodgkin's Lymphoma (NHL)

Activated B-Cell Type Diffuse Large B-Cell Lymphoma (ABC-DLBCL)

Mantle Cell Lymphoma (MCL)

Chronic Lymphocytic Leukemia (CLL)

Small Lymphocytic Lymphoma (SLL)

Intervention/treatment

XL114

Phase

Phase 1

Study Type : Interventional
Estimated Enrollment : 2 participants
Masking : None (Open Label)
Primary Purpose : Treatment
Official Title : A Dose-Escalation and Expansion Study of the Safety and Pharmacokinetics of XL114 Administered in Subjects With Non-Hodgkin's Lymphoma
Actual Study Start Date : April 12, 2022
Estimated Primary Completion Date : November 1, 2022
Estimated Study Completion Date : November 1, 2022
Arm Intervention/treatment

Experimental: XL114 Dose-Escalation Cohorts

Subjects (Cohort A1-An) will accrue in cohorts of 3-12 subjects in a i3+3 design.

Drug: XL114

Experimental: XL114 Expansion Cohorts

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).

Drug: XL114
Ages Eligible for Study: 18 Years
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No
Criteria
Inclusion Criteria
  • Dose-Escalation Stage (Cohort A) and Cohort-Expansion Stage (B-E): The subject has received standard life-prolonging therapies or are not qualified to receive such therapies.
  • Dose-Escalation Stage (Cohort A): Subjects with histologically documented diagnosis of B-cell or T-cell Non-Hodgkin's Lymphoma as defined by the World Health Organization (WHO) classification. Note: Refer to exclusion criteria for lymphoma subtypes which are excluded from study participation.
  • Cohort-Expansion Stage Cohort B (ABC-DLBCL subtype): Subjects with histologically documented activated B-cell diffuse large B-cell lymphoma (ABC-DLBCL) subtype. Note: De novo or transformed diffuse large B-cell lymphoma (DLBCL) from previously diagnosed indolent lymphoma (eg, follicular lymphoma) is allowed.
  • Cohort-Expansion Stage Cohort C (MCL): Subjects with histologically documented MCL with monoclonal B-cells that show a chromosome translocation t(11;14)(q13;q32) and/or overexpression of cyclin D1.
  • Cohort-Expansion Stage Cohort D (CLL/SLL): Subjects with histologically documented CLL/SLL per the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines.
  • Cohort-Expansion Stage Cohort E, Biomarker Cohort (ABC-DLBCL, MCL, and SLL): Subjects with ABC-DLBCL, MCL, and SLL that fulfill the subject disease characteristics criteria as described for Cohorts B, C, or D.
  • Cohort-Expansion Stage: Subjects with ABC-DLBCL, MCL, and SLL must have measurable disease by revised criteria for response assessment of lymphoma.
  • Cohort-Expansion Stages: Must have archival tumor tissue available, which was collected up to 2 years prior to consent for this study. If archival tumor tissue is not available, a fresh tumor biopsy may be obtained (if safe to acquire) up to 60 days prior to first dose.
  • Biomarker Cohort: Subjects must provide a fresh tumor biopsy up to 60 days prior to first dose, at week 2, day 1 (W2D1) after initiation of XL114, and at disease progression. Note: The tumor tissue requirement in the Expansion and Biomarker cohorts doesn't apply for subjects with CLL.
  • Recovery to baseline or ≤ Grade 1 severity (Common Terminology Criteria for Adverse Events version 5 [CTCAE v5]) from AEs, unless AEs are clinically nonsignificant or stable.
  • Left ventricular ejection fraction (LVEF) > 50% as determined by echocardiogram (ECHO) or multigated acquisition (MUGA) scan per local standard.
  • Age 18 years or older on the day of consent.
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1
  • Adequate organ and marrow function
  • Sexually active fertile subjects and their partners must agree to highly effective methods of contraception.
  • Female subjects of childbearing potential must not be pregnant at screening.
Exclusion Criteria
  • Receipt of prior therapies as defined in the protocol
  • The following lymphoma types/manifestations are not eligible for this study: Burkitt's lymphoma (BL), Burkitt-like lymphoma (BLL), lymphoblastic lymphoma/leukemia (LBL), post-transplant lymphoproliferative disease (PTLD), primary mediastinal (thymic) large B-cell lymphoma (PMBL), lymphomas involving the central nervous system (CNS) or meninges
  • History of autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP).
  • History of solid organ or allogeneic hematopoietic stem cell transplantation.
  • Concomitant anticoagulation with the oral anticoagulants apixaban, betrixaban, rivaroxaban, and dabigatran.
  • Use of a strong inhibitor or inducer of cytochrome P450 3A4 (CYP3A4) within 5 half-lives or 4 weeks prior to first dose of study treatment, whichever is shorter.
  • Uncontrolled, significant intercurrent or recent illness
  • Major surgery (eg, GI surgery) within 3 weeks before first dose of study treatment.
  • Corrected QT interval calculated by the Fridericia formula (QTcF) > 470 ms per electrocardiogram (ECG).
  • Pregnant or lactating females.
  • Inability to swallow XL114 tablets.
  • Diagnosis of another malignancy within 2 years before first dose of study treatment, except for superficial skin cancers, or localized, low-grade tumors deemed cured and not treated with systemic therapy
Study of XL114 in Subjects With Non-Hodgkin's Lymphoma

Location Details

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Study of XL114 in Subjects With Non-Hodgkin's Lymphoma

How to Participate

Want to participate in this study, select a site at your convenience, send yourself email to get contact details and prescreening steps.

Locations

Not yet recruiting

United States, Arizona

Development Clinical Site #x

Tucson, Arizona, United States, 85719

Not yet recruiting

United States, Indiana

Development Clinical Site #1

Indianapolis, Indiana, United States, 46250

Not yet recruiting

United States, Pennsylvania

Exelixis Clinical #4

Pittsburgh, Pennsylvania, United States, 15224

Not yet recruiting

United States, Washington

Development Clinical Site #2

Spokane, Washington, United States, 99208