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Phase I/II, First in Human, Dose Escalation Trial of TL 895 in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia or Relapsed/Refractory Small Lymphocytic Lymphoma

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ClinicalTrials.gov Identifier: NCT02825836
Recruitment Status : Recruiting
First Posted : July 7, 2016
Last Update Posted : April 14, 2021
Sponsor:
Information provided by (Responsible Party):
Telios Pharma, Inc.

Study Description
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Brief Summary:

The purpose of this research study is to determine the safety and tolerability of TL-895. There are 2 parts of this study. Part 1 tested increasing doses of TL-895 to identify the recommended safe dose for participants with relapsed/refractory (R/R) B cell malignancies who failed at least 1 but no more than 3 prior therapies. Part 1 of this study is no longer enrolling participants.

Part 2 of this study will test different doses of TL-895 in participants with R/R CLL or SLL who have failed at least 1 prior therapy. Part 2 of this study is randomized (like the flip of a coin) to receive a specific treatment dose. If someone participates in Part 2, the dose they receive will be either 100mg twice a day or 150mg twice a day. Every participant in this study will receive TL-895.


Condition or disease Intervention/treatment Phase
Relapsed/Refractory B Cell Malignancies Mantle Cell Lymphoma and Diffuse Large B Cell Lymphoma Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Drug: TL-895 Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 58 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II, First in Human, Dose Escalation Trial of TL 895 in Subjects With Relapsed/Refractory B-Cell Malignancies and Expansion in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia or Relapsed/Refractory Small Lymphocytic Lymphoma
Actual Study Start Date : August 26, 2016
Estimated Primary Completion Date : February 1, 2024
Estimated Study Completion Date : February 1, 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: TL-895 80/160 mg QD
Participants received TL-895 80 mg powder in capsule (PiC) orally once daily (OD) for 3 days followed by TL-895 160 mg OD in fasted state for 28 days in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.
 Drug: TL-895
All participants will receive TL-895 at the dose assigned at enrollment until disease progression, withdrawal of consent, or discontinuation from the study.
Experimental: TL-895 300 mg QD
Participants received TL-895 300 mg PiC orally OD in fasted state for 28 days in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.
 Drug: TL-895
All participants will receive TL-895 at the dose assigned at enrollment until disease progression, withdrawal of consent, or discontinuation from the study.
Experimental: TL-895 600 mg QD
Participants received TL-895 600 mg PiC orally OD in fasted state for 28 days in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.
 Drug: TL-895
All participants will receive TL-895 at the dose assigned at enrollment until disease progression, withdrawal of consent, or discontinuation from the study.
Experimental: TL-895 300 mg BID
Participants received TL-895 300 mg PiC orally twice daily (BID) in fasted state for 28 days in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.
 Drug: TL-895
All participants will receive TL-895 at the dose assigned at enrollment until disease progression, withdrawal of consent, or discontinuation from the study.
Experimental: TL-895 900 mg QD
Participants received TL-895 900 mg PiC orally QD in fasted state for 28 days in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.
 Drug: TL-895
All participants will receive TL-895 at the dose assigned at enrollment until disease progression, withdrawal of consent, or discontinuation from the study.
Experimental: TL-895 100 mg BID
Participants received TL-895 100 mg BID orally BID with food for 28 days in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.
 Drug: TL-895
All participants will receive TL-895 at the dose assigned at enrollment until disease progression, withdrawal of consent, or discontinuation from the study.
Experimental: TL-895 150 mg BID
Participants received TL-895 150 mg BID orally BID with food for 28 days in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.
 Drug: TL-895
All participants will receive TL-895 at the dose assigned at enrollment until disease progression, withdrawal of consent, or discontinuation from the study.


Outcome Measures
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Primary Outcome Measures :
  1. Part 1 (Dose Escalation): DLTs (Dose Limiting Toxicities) during Cycle 1 [ Time Frame: Baseline up to the end of cycle 1 (28 days) ]
    DLT is defined as any of the adverse event (AEs) of a certain grade or above, related to drug.

  2. Part 2 (Dose Expansion): Overall Response Rate (ORR) [ Time Frame: Baseline up to end of study (2 years after last patient enrolled) ]
    The proportion of subjects achieving CR, CRi, nodular partial response (nPR), partial response (PR), or PR with lymphocytosis (PR-L) at any time while on the study based on iwCLL response criteria (2), as assessed by investigators


Secondary Outcome Measures :
  1. Part 1 (Dose Escalation): Best Overall Response (BOR)/Progression Free Survival (PFS) [ Time Frame: Baseline up to 6 months on treatment ]
    Defined by the length of time during the treatment of the disease, that a participant lives with the disease but it does not get worse based on investigator assessments

  2. Part 2 (Dose Expansion): Overall CR/CRi rate [ Time Frame: Baseline up to end of study (2 years after last patient enrolled) ]
    The proportion of subjects achieving CR/CRi based on iwCLL response criteria

  3. Part 2: Duration of Clinical Response (DOR) [ Time Frame: Baseline up to end of study (2 years after last patient enrolled) ]
    Time from initial response to disease progression or death from any cause

  4. Part 2: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Baseline up to end of study (2 years after last patient enrolled) ]
    Incidence, nature, severity of treatment-emergent adverse events (TEAEs), and deaths, including cause of death, from screening up to the end of study visit of participants with CLL/SLL who have failed at least 1 line of therapy

  5. Part 2: Assessment of Safety and Tolerability via Clinical Measurements [ Time Frame: Baseline up to end of study (2 years after last patient enrolled) ]
    Assessments including but not limited to clinical laboratory measurements, ECGs, vital signs, and ECOG performance


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Relapsed/refractory CLL or relapsed/refractory SLL
  • ECOG performance status of ≤ 2
  • Adequate hematologic, hepatic, and renal functions

Exclusion Criteria

  • Prior treatment with any BTK or PI3K inhibitors
  • History of major organ transplant
  • Women who are pregnant or breastfeeding
Contacts and Locations
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Information from the National Library of Medicine

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): NCT02825836


Contacts
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Contact: John Mei jmei@teliospharma.com
Contact: Nikki Stuart nzona@teliospharma.com

Locations
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United States, Ohio
Ohio State University Wexner Medical Center Recruiting
Columbus, Ohio, United States, 43210
Principal Investigator: Seema Bhat, MD         
United States, Tennessee
The West Clinic Recruiting
Germantown, Tennessee, United States, 38138
Principal Investigator: Jason C. Chandler, MD         
Italy
Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi - Istituto di Ematologia e Oncologia Medica Completed
Bologna, Italy
Poland
Malopolskie Centrum Medyczne Active, not recruiting
Krakow, Poland
United Kingdom
Barts Hospital - Cancer Centre Completed
London, United Kingdom
University College London Hospitals - NIHR/Wellcome Trust Active, not recruiting
London, United Kingdom
Derriford Hospital - Dept of Haematology Active, not recruiting
Plymouth, United Kingdom
Sponsors and Collaborators
Telios Pharma, Inc.
More Information
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Publications:
Eugenio Gaudio, Chiara Tarantelli, Emanuele Zucca, Davide Rossi, Anastasios Stathis, Francesco Bertoni. The two novel BTK-inhibitors M2951 and M7583 show in vivo anti-tumor activity in pre-clinical models of B cell lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4182. doi:10.1158/1538-7445.AM2017-4182
Samantha M. Goodstal, Jianguo Ma, Jing Lin, Timothy Crandall, Lindsey Crowley, Andrew Bender, Riham Iadevaia and Anderson Clark. M7583 Is a Highly Selective and Potent Second Generation BTK Inhibitor for Treatment of B-Cell Malignancies. Blood 2017 130:3845.
Wojciech Jurczak, Simon Rule, William Townsend, David Tucker, Martin Dyroff, Barbara Sarholz, Jürgen Scheele, John G. Gribben and Pier Luigi Zinzani. First in Human, Phase I/II Trial of the Bruton's Tyrosine Kinase Inhibitor (BTKi) M7583 in Patients with B Cell Malignancies: Study Design and Initial Outcomes. Blood 2017 130:2778.
Simon Rule, David Tucker, Anup Kalapur, Barbara Sarholz, Jürgen Scheele, Pier Luigi Zinzani. Phase I/II, first in human trial of the Bruton's tyrosine kinase inhibitor (BTKi) M7583 in patients with B cell malignancies. J Clin Oncol 35, 2017 (suppl; abstr e14101).

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Responsible Party: Telios Pharma, Inc.
ClinicalTrials.gov Identifier: NCT02825836    
Other Study ID Numbers: MS200662_0001
2016-000286-23 ( EudraCT Number )
First Posted: July 7, 2016    Key Record Dates
Last Update Posted: April 14, 2021
Last Verified: April 2021
Keywords provided by Telios Pharma, Inc.:
TL-895
Tyrosine Kinase Inhibitor
Lymphoma
Open
 Phase I
Phase II
CLL
SLL
Additional relevant MeSH terms:
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Lymphoma
Leukemia
Neoplasms
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
 Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin