Study of Oral LOXO-338 in Patients With Advanced Blood Cancers
- for people ages 18 years and up (full criteria)
- at UCSF
- study startedestimated completion
The purpose of this study is to find out whether the study drug, LOXO-338, is safe and effective in patients with advanced blood cancer. Patients must have already received standard therapy. The study may last up to approximately 3 years.
A Phase 1 Study of Oral LOXO-338, a Selective BCL-2 Inhibitor, in Patients With Advanced Hematologic Malignancies
This study will be conducted in 2 parts. Part 1 will evaluate LOXO-338 as monotherapy. If safety and initial evidence of efficacy of LOXO-338 monotherapy are confirmed, part 2 will evaluate the combination of LOXO-338 with the highly selective, noncovalent Bruton's tyrosine kinase (BTK) inhibitor, pirtobrutinib (LOXO-305).
Leukemia, Lymphocytic, Chronic, B-Cell Lymphoma, B-cell Marginal Zone Lymphoma, Non-Hodgkin Multiple Myeloma B-cell Lymphoma Waldenstrom Macroglobulinemia Lymphoma, Mantle-Cell BTKi Hematologic disease Small lymphocytic lymphoma BCL-2 inhibitor CLL SLL NHL Lymphoma Lymphoma, B-Cell Leukemia, Lymphoid LOXO-338 Pirtobrutinib LOXO-338 (Monotherapy)
You can join if…
Open to people ages 18 years and up
- B-cell malignancy.
- Patients must have received prior therapy.
- Patients must have an objective indication for therapy.
- Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1.
- Anticipated life expectancy of greater than or equal to (≥) 12 weeks.
- Adequate bone marrow function.
- Adequate hepatic function.
- Creatinine clearance of ≥ 60 milliliters (mL)/minute.
- Ability to swallow tablets.
- Ability to comply with outpatient treatment, laboratory monitoring, and required clinic visits for the duration of study participation.
- Prior treatment-related adverse events (AEs) must have recovered to grade less than or equal to (≤) 1 or pretreatment baseline, with the exception of alopecia.
- Men with partners of childbearing potential or women of childbearing potential (WOCBP) must agree to use highly effective birth control.
- WOCBP must not be pregnant.
- Additional Inclusion Criteria for Patients with AL Amyloidosis
- In Part 1 Dose Expansion, patients with AL amyloidosis are eligible based on prior detection of primary systemic light-chain amyloidosis.
- Must have measurable disease of AL amyloidosis.
- Prior local fluorescence in-situ hybridization (FISH) testing results for t(11;14) are required to be submitted prior to enrollment.
You CAN'T join if...
- Prior to identification of an appropriate RP2D (Dose Expansion) of LOXO-338, a history of known, active or suspected:
- Richter's transformation to diffuse large B-cell lymphoma (DLBCL), prolymphocyticleukemia, or Hodgkin lymphoma
- Transformed low grade lymphoma
- Burkitt or Burkitt-like lymphoma
- Diffuse large B-cell lymphoma
- AL amyloidosis
- Multiple myeloma
- Lymphoblastic lymphoma or leukemia
- Posttransplant lymphoproliferative disorder
- Known or suspected history of central nervous system (CNS) involvement.
- History of allogeneic or autologous stem cell transplant (SCT) or chimeric antigen receptor-modified T cell (CAR-T) therapy within the past 60 days and with any of the following:
- Active graft versus host disease (GVHD)
- Cytopenias from incomplete blood cell count recovery post-transplant or CAR-T therapy
- Need for anti-cytokine therapy for toxicity from CAR-T therapy; residual symptoms of neurotoxicity Grade > 1 from CAR-T therapy
- Ongoing immunosuppressive therapy
- Known human immunodeficiency virus (HIV) positive, regardless of cluster of differentiation 4 (CD4) count. Unknown or negative status eligible.
- Inability to take necessary uric acid lowering agents (i.e., allopurinol, rasburicase, orfebuxostat).
- Concurrent anticancer therapy.
- Concurrent treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers that can include antifungals.
- Use of ≥ 20 milligrams (mg) prednisone once a day (QD) or equivalent dose of steroid per day, within 7 days of start of study treatment. Patients may not be on any dose of prednisone intended for antineoplastic use.
- Vaccination with a live vaccine within 28 days prior to start of study therapy.
- Major surgery within four weeks of planned start of study therapy Prolongation of the QT interval corrected by Fridericia's Formula for heart rate (QTcF) greater than (>) 470 milliseconds (msec).
- Clinically significant cardiovascular disease.
- Female patient who is pregnant or lactating.
- Active second malignancy which may preclude assessment of DLT.
- Clinically significant active malabsorption syndrome including surgical resection of small intestine or other condition likely to affect gastrointestinal (GI) absorption of the orally administered study drugs.
- Active hepatitis B or C infection.
- Evidence of other clinically significant uncontrolled condition(s) including, but not limited to, uncontrolled systemic infection (viral, bacterial, or fungal) or other clinically significant active disease process.
- Active uncontrolled auto-immune cytopenia.
- Additional Exclusion Criteria for Patients with AL Amyloidosis (Part 1 Dose-Expansion)
- Previous or current diagnosis of symptomatic MM.
- Heart failure that, in the opinion of the Investigator, is on the basis of ischemic heart disease.
- Supine systolic blood pressure < 90 mmHg, or symptomatic orthostatic hypotension in the absence of volume depletion.
- N-terminal pro hormone natriuretic peptide (NT-proBNP) > 8500 ng/L (or BNP > 700 ng/L if NT-proBNP is not available by local or central testing).
- Additional exclusion criteria for patients enrolled to part 2: LOXO-338 and pirtobrutinib combination
- Prior progression or intolerance to pirtobrutinib.
- Patients requiring therapeutic anticoagulation with warfarin.
- Known hypersensitivity to any component or excipient of pirtobrutinib.
- In patients with history of myocardial infarction or congestive heart failure, documented left ventricular ejection fraction (LVEF) by any method of ≤ 45 percent (%) in the 12 months prior to planned start of study treatment.
- History of uncontrolled or symptomatic arrhythmias including grade ≥ 3 arrhythmia on a prior BTK inhibitor.
- History of major bleeding on a prior BTK inhibitor.
- Current treatment with strong permeability glycoprotein (P-gp) inhibitors.
- University of California San Francisco, Medical Center at Paranassus
accepting new patients
San Francisco California 94117 United States
- Swedish Medical Center
accepting new patients
Seattle Washington 98104 United States
- accepting new patients
- Start Date
- Completion Date
- Eli Lilly and Company
- Phase 1 research study
- Study Type
- Expecting 316 study participants
- Last Updated