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A Study of Oral LOXO-305 in Patients With Previously Treated CLL/SLL or NHL

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ClinicalTrials.gov Identifier: NCT03740529
Recruitment Status : Recruiting
First Posted : November 14, 2018
Last Update Posted : October 25, 2019
Sponsor:
Information provided by (Responsible Party):
Loxo Oncology, Inc.

Tracking Information
First Submitted Date  ICMJE November 6, 2018
First Posted Date  ICMJE November 14, 2018
Last Update Posted Date October 25, 2019
Actual Study Start Date  ICMJE November 16, 2018
Estimated Primary Completion Date October 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 12, 2018)
  • Maximum Tolerated Dose (MTD) [ Time Frame: Up to 24 Months ]
    Phase I
  • Recommended dose for further study [ Time Frame: Up to 24 Months ]
    Phase I
  • To assess the preliminary anti-tumor activity of LOXO-305 based on ORR as assessed by an Independent Review Committee (IRC). [ Time Frame: Up to 24 months ]
    Phase II
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03740529 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 12, 2018)
  • To determine the safety profile and tolerability of LOXO-305 including acute and chronic toxicities by collecting and evaluating Adverse events and treatment emergent adverse events. [ Time Frame: Up to 24 Months ]
    Phase I
  • To characterize the pharmacokinetics (PK) properties of LOXO-305 by collecting and evaluating serum at protocol specified time points. [ Time Frame: Up to 24 Months ]
    Phase I
  • To assess the preliminary anti-tumor activity of LOXO-305 based on overall response rate (ORR) as assessed by investigator. [ Time Frame: Up to 24 Months ]
    Phase I
  • ORR as assessed by the Investigator. [ Time Frame: Up to 24 Months ]
    Phase II
  • Best overall response (BOR) as assessed by the Investigator and IRC. [ Time Frame: Up to 24 Months ]
    Phase II
  • Duration of response (DOR) as assessed by the Investigator and IRC. [ Time Frame: Up to 24 Months ]
    Phase II
  • Progression free survival (PFS) as assessed by the Investigator and IRC. [ Time Frame: Up to 24 Months ]
    Phase II
  • Overall survival (OS). [ Time Frame: Up to 24 Months ]
    Phase II
  • To determine the safety profile and tolerability of LOXO-305 including acute and chronic toxicities by collecting and evaluating Adverse events and treatment emergent adverse events. [ Time Frame: Up to 24 Months ]
    Phase II
  • To characterize the pharmacokinetics (PK) properties of LOXO-305 by collecting and evaluating serum at protocol specified time points. [ Time Frame: Up to 24 Months ]
    Phase II
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Oral LOXO-305 in Patients With Previously Treated CLL/SLL or NHL
Official Title  ICMJE A Phase 1/2 Study of Oral LOXO-305 in Patients With Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) or Non-Hodgkin Lymphoma (NHL)
Brief Summary This is an open-label, multi-center Phase 1/2 study of oral LOXO-305 in patients with CLL/SLL and NHL who have failed or are intolerant to standard of care.
Detailed Description This study includes 2 parts: phase 1 (dose escalation) and phase 2 (dose expansion). In phase 1, patients will be enrolled using an accelerated titration design. The starting dose of LOXO-305 in oral tablet form is 25 mg/day (e.g., 25 mg once daily [QD]). Once the MTD and/or RP2D is identified, patients will be enrolled to one of six phase 2 dose expansion cohorts depending on tumor histology, tumor genotype, and prior treatment history. Cycle length will be 28 days.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Chronic Lymphocytic Leukemia
  • Waldenstrom Macroglobulinemia
  • Mantle Cell Lymphoma
  • Marginal Zone Lymphoma
  • B-cell Lymphoma
  • Small Lymphocytic Lymphoma
Intervention  ICMJE Drug: LOXO-305
Oral LOXO-305
Study Arms  ICMJE
  • Experimental: LOXO-305
    Phase I: Dose Escalation and determination of MTD; multiple dose levels of LOXO-305 to be evaluated
    Intervention: Drug: LOXO-305
  • Experimental: CLL/SLL Failed BTKi C481 mutant
    Phase II: CLL/SLL Failed BTKi C481 mutant will receive the recommended Phase II dose of LOXO-305.
    Intervention: Drug: LOXO-305
  • Experimental: CLL/SLL Failed BTKi no C481 mutation
    Phase II: CLL/SLL Failed BTKi no C481 mutation will receive the recommended Phase II dose of LOXO-305.
    Intervention: Drug: LOXO-305
  • Experimental: WM/MCL/MZL Failed BTKi C481 mutant
    Phase II: WM/MCL/MZL Failed BTKi C481 mutant will receive the recommended Phase II dose of LOXO-305.
    Intervention: Drug: LOXO-305
  • Experimental: WM/MCL/MZL Failed BTKi no C481 mutation
    Phase II: WM/MCL/MZL Failed BTKi no C481 mutation will receive the recommended Phase II dose of LOXO-305.
    Intervention: Drug: LOXO-305
  • Experimental: CLL/SLL/WM/MCL/MZL/other NHL intolerant to prior BTKi
    Phase II: CLL/SLL/WM/MCL/MZL/other NHL intolerant to prior BTKi will receive the recommended Phase II dose of LOXO-305.
    Intervention: Drug: LOXO-305
  • Experimental: Other
    Phase II: Unknown BTK C481 substitution mutation and other patients not meeting the definitions of Cohorts 1 through 5 will receive the recommended Phase II dose of LOXO-305.
    Intervention: Drug: LOXO-305
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 12, 2018)
190
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2021
Estimated Primary Completion Date October 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically confirmed CLL/SLL or NHL intolerant to standard of care therapies.
  • Histologically confirmed CLL/SLL or NHL which has failed standard of care therapies
  • ≥ 2 prior lines of therapy.
  • For initial phase 1 patients, able to tolerate potentially subtherapeutic doses of LOXO-305 for the 28-day DLT window in the opinion of the investigator and with documented sponsor approval.
  • Eastern Cooperative Oncology Group (ECOG) 0-2.
  • Adequate hematologic, hepatic and renal function.
  • Ability to receive study drug therapy orally.
  • Willingness of men and women of reproductive potential to observe conventional and effective birth control.

Exclusion Criteria:

  • Transformation (e.g., Richter's transformation, prolymphocytic leukemia, transformed NHL, blastoid lymphoma) prior to planned start of LOXO-305.
  • Investigational agent or anticancer therapy within 2 weeks prior to planned start of LOXO-305. In addition, no concurrent investigational therapy is permitted.
  • Major surgery within 4 weeks prior to planned start of LOXO-305.
  • Radiotherapy with a limited field of radiation for palliation within 7 days of the first dose of study treatment.
  • Pregnancy or lactation.
  • Patients requiring therapeutic anticoagulation.
  • Any unresolved toxicities from prior therapy greater than CTCAE (version 5.0) Grade 2 or greater at the time of starting study treatment except for alopecia.
  • History of allogeneic or autologous stem cell transplant (SCT) or chimeric antigen receptor-modified T-cell (CAR-T) therapy within the past 100 days (180 days before the PK trigger).
  • Known central nervous system (CNS) involvement by lymphoma.
  • Active uncontrolled auto-immune cytopenia.
  • Clinically significant, uncontrolled cardiac, cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of LOXO-305.
  • Active uncontrolled systemic bacterial, viral, fungal or parasitic infection.
  • Tested positive for Human Immunodeficiency Virus (HIV) is excluded.
  • Clinically significant active malabsorption syndrome.
  • Current treatment with certain strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers and/or strong P-gp inhibitors
  • Treatment with proton pump inhibitors (PPIs) within 7 days of starting LOXO-305.

Active second malignancy unless in remission and with life expectancy > 2 years.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Patient Advocacy 1-855-LOXO-305 clinicaltrials@loxooncology.com
Listed Location Countries  ICMJE Australia,   France,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03740529
Other Study ID Numbers  ICMJE LOXO-BTK-18001
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Loxo Oncology, Inc.
Study Sponsor  ICMJE Loxo Oncology, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Nora Ku, MD LOXO Oncology
PRS Account Loxo Oncology, Inc.
Verification Date November 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP