Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UCSF
Dates
study started
estimated completion

Description

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.

Official Title

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)

Details

This study includes 3 parts: phase 1 (LOXO-305 monotherapy dose escalation and dose expansion), phase 1b (LOXO-305 combination therapy dose expansion), and phase 2 (LOXO-305 monotherapy 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 in phase 1 dose escalation, enrollment will continue to phase 1 dose expansion and can commence to phase 1b (Arms A and B). For phase 2, patients will be enrolled to one of seven phase 2 dose expansion cohorts depending on tumor histology and prior treatment history. Cycle length will be 28 days.

Keywords

Chronic Lymphocytic Leukemia Waldenstrom Macroglobulinemia Mantle Cell Lymphoma Marginal Zone Lymphoma B-cell Lymphoma Small Lymphocytic Lymphoma Loxo LOXO-305 BTK Bruton's tyrosine kinase CLL SLL NHL C481S C481 Ibrutinib Acalabrutinib Zanubrutinib BGB-3111 GS-4059 ONO-4059 Tirabrutinib Non-Hodgkin Lymphoma BTK Intolerant C481S Mutation DLBCL (Diffuse Large B-cell lymphoma) Follicular Lymphoma PI3KD Idelalisib Umbralisib BCL2 Venetoclax Rituximab Primary CNS Lymphoma Richter's Transformation Lymphoma Leukemia Leukemia, Lymphoid Leukemia, Lymphocytic, Chronic, B-Cell Lymphoma, B-Cell Lymphoma, Mantle-Cell Lymphoma, B-Cell, Marginal Zone

Eligibility

You can join if…

Open to people ages 18 years and up

  • Histologically confirmed CLL/SLL, WM, or NHL intolerant to either ≥ 2 prior standard of care regimens given in combination or sequentially OR have received 1 prior BTK inhibitor-containing regimen when a BTK inhibitor is approved as first line therapy (Phase 1) OR with prior treatment defined by phase 2 cohort (Phase 2 Patients only).
  • Adequate hematologic function (Phase 1 and 1b Patients only).
  • Responsive to transfusion support if given for thrombocytopenia or anemia (Phase 1 and 1b Patients only).
  • Histologically confirmed relapsed/recurrent CLL in whom venetoclax is appropriate standard salvage treatment; no prior venetoclax is permitted (Phase 1b Arm A Patients only).
  • Histologically confirmed relapsed/refractory CLL in whom venetoclax + rituximab is appropriate standard salvage treatment; no prior venetoclax is permitted (Phase 1b Arm B Patients only).
  • Eastern Cooperative Oncology Group (ECOG) 0-2.
  • Adequate hepatic and renal function.
  • Ability to receive study drug therapy orally.
  • Willingness of men and women of reproductive potential (defined as following menarche and not postmenopausal [and 2 years of non-therapy-induced amenorrhea] or surgically sterile) to observe conventional and effective birth control.

You CAN'T join if...

  • Investigational agent or anticancer therapy within 5 half-lives prior to planned start of specified study therapy 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 systemic anticancer therapy is permitted.
  • Major surgery within 4 weeks prior to planned start of specified study therapy.
  • 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 with warfarin.
  • 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 60 days (180 days before the PK trigger) prior to planned start of specified study therapy.
  • 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 and enrolled to phase 2 Cohort 7 if a compelling clinical rationale is provided by the Investigator and with documented Sponsor approval.
  • Active uncontrolled auto-immune cytopenia where new therapy introduced or concomitant therapy escalated within the 4 weeks prior to study enrollment is required to maintain adequate blood counts.
  • 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.
  • Patients who have tested positive for Human Immunodeficiency Virus (HIV) are excluded. For patients with unknown HIV status, HIV testing will be performed at Screening and result should be negative for enrollment.
  • Clinically significant active malabsorption syndrome.
  • Current treatment with certain strong CYP3A4 inhibitors or inducers and/or strong P-gp inhibitors.
  • For patients enrolled to phase 1b Arm A or B: Patients with prior treatment with venetoclax or other BCL-2 inhibitors.
  • Prior treatment with LOXO-305.
  • Active second malignancy unless in remission and with life expectancy > 2 years.
  • Known hypersensitivity to any component or excipient of LOXO-305.
  • For patients enrolled to phase 1b Arm B: Patients with prior significant hypersensitivity, allergy, or anaphylactic reaction to rituximab/biosimilar requiring discontinuation.
  • Patients with prior significant hypersensitivity to rituximab requiring discontinuation, prior allergic or anaphylactic reaction to rituximab (Phase 1b Arm B Patients only).

Locations

  • University of California, San Francisco accepting new patients
    San Francisco California 94143 United States
  • Swedish Cancer Institute accepting new patients
    Seattle Washington 98104 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Loxo Oncology, Inc.
ID
NCT03740529
Phase
Phase 1/2
Study Type
Interventional
Last Updated