Refractory Hematologic Malignancy

This clinical trial tests a new mobile health application (app) called Planning Advance Care Together (PACT) to help people with cancer talk about and plan for advance care planning (the care they would want if they were unable to communicate) with their loved ones and doctors. The development of the PACT mobile app may help future patients incorporate their social network (typically, but not exclusively, family) into the advance care planning process.

Human gene therapy products are designed to achieve therapeutic effect through genetic modifications of human cells using retroviral or lentiviral vectors, resulting in permanent or long-acting changes in the human body. With this genetic modification comes risk of undesirable adverse events. Due to this risk, the Food and Drug Administration (FDA) and the Center for Biologics Evaluation and research (CBER) require long-term follow-up (15 years) of participants that receive investigational gene therapy products that meet defined criteria. This protocol will provide a mechanism by which to appropriately monitor participants that have received a genetically modified cellular product on a St. Jude initiated study.

This is a multi-center, open-label study to evaluate the safety, pharmacokinetics (PK), and anti-cancer activity of oral administration of emavusertib alone or in combination with ibrutinib in adult participants with relapsed or refractory (R/R) hematologic malignancies. This trial will be completed in four parts. In Part A1, emavusertib will be evaluated first in a dose escalating monotherapy setting to establish the safety and tolerability (complete). In Part A2, emavusertib will be evaluated in combination with ibrutinib at 560 milligrams (mg) once daily (QD) or 420 mg QD as indicated by disease (Part A2 complete). Part B will comprise 2 cohorts to assess safety and efficacy of emavusertib in combination with ibrutinib in participants with R/R primary central nervous system lymphoma (PCNSL) who have directly progressed on a bruton tyrosine kinase inhibitor (BTKi). In this part of the study, emavusertib will be dosed at 100 mg or 200 mg twice daily (BID) in combination with ibrutinib in 28-day treatment cycles. Part C will comprise 3 treatment arms in the second-line setting to assess the efficacy and safety of emavusertib monotherapy, ibrutinib monotherapy, and emavusertib in combination with ibrutinib in participants with R/R PCNSL who are naïve to BTKi treatment. In this part of the study, eligible second-line participants with R/R PCNSL who are naïve to BTKi treatment will be randomized 1:1:1 to 1 of 3 treatment arms: (1) emavusertib 200 mg BID, (2) ibrutinib 560 mg QD, or (3) emavusertib 200 mg BID in combination with ibrutinib 560 mg QD.

The iLTB is a proof-of-concept initiative for children with r/r hematological malignancies, in which available treatment options will be prioritized by actionable events in a harmonized and uniform setting across Europe by a team of biologists, bio-statisticians, bio-informaticians, disease experts, geneticists, flow-experts, clinical trial physicians and also the treating physician. The iLTB will discuss molecular (genetic lesions), immunophenotypic/surface antigen markers information and, if available, drug response profiles to prioritize these events taking into account the treatment history and treatment intention (bridging to hematopoietic stem cell transplanation/CAR-T or palliative) of each patient followed by a registry to monitor how often iLTB advice has been followed, which other therapy was chosen (off-label, compassionate use) and what the patient outcome is at an aggregated level. As such the iLTB is non-interventional as it mainly provides advice and registers data on patients discussed in the iLTB.