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

JRCT ID: jRCT2031200245

Registered date:15/12/2020

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) or Non-Hodgkin Lymphoma (NHL)
• Date of first enrollment: 25/12/2020
• Target sample size: 30
• Countries of recruitment: United States,Japan,United Kingdom,Japan,Italy,Japan,France,Japan,Poland,Japan,Switzerland,Japan,Australia,Japan,South Korea,Japan,Sweden,Japan
• Study type: Interventional
• Intervention(s): Investigational drug LOXO-305 tablets for oral administration

Outcome(s)

Primary Outcome

- MTD/RP2D
- ORR by appropriate disease defined criteria and assessed by IRC

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Histologically confirmed B-cell malignancy (e.g., CLL/SLL, WM, NHL) failed or intolerant to either 2 prior standard of care regimens given in combination or sequentially OR have received 1 prior BTK containing regimen when a BTK inhibitor is approved as first line therapy. For phase 1 confirmation of recommended dose in Japan, patients whose standard therapies are no longer effective or are not considered appropriate or safe in the opinion of the Investigator, are eligible
2. During dose escalation and DLT assessment: Adequate hematologic status that meets pre-defined criteria on or within 7 days of C1D1 before treatment
3. After phase 1 dose escalation and DLT assessment: Responsive to transfusion support if given for thrombocytopenia or anemia
4. Eastern Cooperative Oncology Group (ECOG) 0-1
5. At least 20 years of age
6. Confirmation of availability of tumor sample obtained after most recent treatment
7. Adequate hepatic function with test results that meet all the pre-defined criteria
8. Adequate renal function defined as creatinine clearance >= 30 mL/ minute using Cockcroft/Gault Formula
9. Ability to swallow tablets and comply with outpatient treatment, laboratory monitoring, and required clinic visits for the duration of study participation
10. Willingness of men and women of reproductive potential to observe conventional and effective birth control methods with failure rates of < 1% for the duration of treatment and for 6 months following the last dose of study treatment

Exclude criteria

1. Investigational agent or anticancer therapy within 5 half-lives prior to planned start of LOXO-305 except therapeutic monoclonal antibody treatment must be discontinued a minimum of 4 weeks prior to the first dose of LOXO-305
In addition, no concurrent investigational therapy is permitted
2. Major surgery within 4 weeks prior to planned start of LOXO-305
3. Radiotherapy with a limited field of radiation for palliation within 7 days of the first dose of study treatment, except for patients receiving radiation to more than 30% of the bone marrow or receiving whole brain radiotherapy, which must be completed at least 4 weeks prior to the first dose of study treatment
4. Patients requiring therapeutic anticoagulation with warfarin
5. Any unresolved toxicities from prior therapy greater than CTCAE (version 5.0) Grade 1 at the time of starting study treatment except for alopecia
6. History of allogeneic or autologous stem cell transplant (SCT) or CAR-T therapy within the last 60 days or with any of the following:
a. Active graft versus host disease (GVHD);
b. Cytopenias from incomplete blood cell count recovery post-transplant;
c. Need for anti-cytokine therapy for toxicity from CAR-T therapy; residual symptoms of neurotoxicity > Grade 1 from CAR-T therapy;
d. Ongoing immunosuppressive therapy
7. Known central nervous system (CNS) involvement by systemic lymphoma. Patients with previous treatment for CNS involvement who are neurologically stable and without evidence of disease may be eligible if a compelling clinical rationale is provided by the Investigator and with documented Sponsor approval
8. Active uncontrolled auto-immune cytopenia (e.g., autoimmune hemolytic anemia [AIHA], idiopathic thrombocytopenic purpura [ITP]) where new therapy introduced or concomitant therapy escalated within the 4 weeks prior to study enrollment is required to maintain adequate blood counts
9. Clinically significant, uncontrolled cardiac, cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of LOXO-305, or observed pre-defined ECG findings during Screening
10. Active uncontrolled systemic bacterial, viral, fungal or parasitic infection (except for fungal nail infection), or other clinically significant active disease process which in the opinion of the Investigator and the Sponsor makes it undesirable for the patient to participate in the trial. This includes interstitial lung disease (ILD), severe dyspnea at rest, or requiring oxygen therapy. Screening for chronic conditions is not required. Patients who have a history of ILD are excluded
11. Tested positive for Human Immunodeficiency Virus (HIV) is excluded (due to potential drug-drug interactions between anti-retroviral medications and LOXO-305 and risk of opportunistic infections with both HIV and irreversible BTK inhibitors). For patients with unknown HIV status, HIV testing will be performed at Screening
12. Clinically significant active malabsorption syndrome or other condition likely to affect GI absorption of the study drug
13. Current treatment with certain strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers and/or strong P-gp inhibitors
14. Treatment with PPIs within 7 days of starting LOXO-305
15. Pregnancy or lactation at time of screening. Pregnancy and lactation within 6 months of last dose of LOXO-305 is prohibited. Patients who have stopped breast feeding can be enrolled
16. Active second malignancy unless in remission with life expectancy > 2 years and with documented Sponsor approval
17. Patients with known hypersensitivity to any component or excipient of LOXO-305
18. Have a known active fungal, bacterial, and/or known viral infection, including hepatitis viruses

Related Information

• Primary Sponsor: Tsai E. Donald
• Secondary ID(s): NCT03740529