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Non-Hodgkin's Lymphoma (NHL)Phase 1NCT05144347

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

A Phase 1 study testing XL114 in people with Non-Hodgkin's Lymphoma (NHL) and Activated B-Cell Type Diffuse Large B-Cell Lymphoma (ABC-DLBCL), run by Exelixis at 4 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
XL114
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
4 sitesUnited States
Study dates
12 Apr 2022to 1 Nov 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Exelixis Clinical Site #1

    Indianapolis, Indiana, 46250

  • Exelixis Clinical #4

    Pittsburgh, Pennsylvania, 15224

  • Exelixis Clinical Site #2

    Spokane, Washington, 99208

  • Exelixis Clinical Site #3

    Tucson, Arizona, 85719

Other trials in United States

About this study

Official title: A Dose-Escalation and Expansion Study of the Safety and Pharmacokinetics of XL114 Administered in Subjects With Non-Hodgkin's Lymphoma

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.

Being tested
XL114
Keywords
Mucosa-associated Lymphoid Tissue Lymphoma Translocation Protein 1 (MALT-1), B-cell Malignancies, Fatty Acid Binding Protein 5 (FABP-5)
Medical subject headings
Lymphoma, Non-Hodgkin, Lymphoma, Mantle-Cell, Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • XL114Drug

    Tablets of XL114

Study groups in NCT05144347
Study groupRoleWhat they receive
XL114 Dose-Escalation CohortsExperimentalSubjects (Cohort A1-An) will accrue in cohorts of 3-12 subjects in a i3+3 design.
Receives: Drug: XL114
XL114 Expansion CohortsExperimentalThe 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).
Receives: Drug: XL114

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 4-6 months

  2. 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

    Measured: 4-6 months

Secondary outcomes (11)

  1. 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.

    Measured: 4-6 months

  2. Tolerability of XL114, as evaluated by Dose Intensity, Dose Modifications, and Study Discontinuation due to AEs

    To evaluate the tolerability of XL114 through the evaluation of dose intensity, dose modifications and study treatment discontinuation due to AEs related to XL114.

    Measured: 4-6 months

  3. Dose-Escalation Stage: Time to Maximum Plasma Concentration (Tmax)

    To evaluate the Tmax of XL114.

    Measured: 4-6 months

  4. Dose-Escalation Stage: Maximum Plasma Concentration (Cmax)

    To evaluate the Cmax of XL114.

    Measured: 4-6 months

  5. 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.

    Measured: 4-6 months

  6. Dose-Escalation Stage: Terminal Half-Life

    To evaluate the terminal half-life of XL114.

    Measured: 4-6 months

  7. Dose-Escalation Stage: Apparent Clearance (CL/F)

    To evaluate the CL/F of XL114.

    Measured: 4-6 months

  8. 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.

    Measured: 4-6 months

  9. 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.

    Measured: 4-6 months

  10. 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.

    Measured: 4-6 months

  11. Cohort-Expansion Stage: Overall Survival (OS) of XL114

    To evaluate duration of overall survival (OS)

    Measured: 4-6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Dec 2021
  2. Study start12 Apr 2022
  3. Primary completion1 Nov 2022
  4. Study completion1 Nov 2022

Why it stopped: Due to Sponsor reasons.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
Dose-escalation followed by Cohort-expansion in NHL-specific expansion cohorts
Masking
None (open label)
Enrolment
2 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05144347
Sponsor's protocol ID
XL114-101
Status last verified
Jul 2023
First submitted
10 Nov 2021
Last updated
11 Jul 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing XL114 in people with Non-Hodgkin's Lymphoma (NHL) and Activated B-Cell Type Diffuse Large B-Cell Lymphoma (ABC-DLBCL), run by Exelixis at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 11 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Due to Sponsor reasons.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose-Escalation Stage: Recommended Dose (RD) and/or Maximum Tolerated Dose (MTD) for XL114 (time frame: 4-6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05144347.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jul 2023.

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