Several clinical trials investigating new drugs in the treatment of leukemia and lymphoma have started in recent months. Maybe one of your patients could benefit from taking part.
Newly diagnosed, previously untreated acute myeloid leukemia (AML). Adult patients with this type of AML who are not eligible for intensive chemotherapy can join a randomized, double-blind, phase 3 trial of the investigational macrophage checkpoint inhibitor magrolimab (developed by Gilead). This is a first-in-class agent that interferes with the recognition of CD47 on the surface of tumor cells ― the “don’t eat me” signal by which cancer cells evade immune destruction. In this trial, all participants will take daily tablets of venetoclax (Venclexta) and receive intravenous (IV) or subcutaneous (SC) azacitidine (Vidaza) approximately 1 week in 4. Participants will also receive 10 escalating doses of IV magrolimab or a placebo infusion over 6 weeks, then every 2 weeks thereafter. Complete remission (CR) and overall survival (OS) are primary endpoints. Quality of life (QoL) is a secondary measure. Sites in 11 US states and 16 countries started recruiting for 432 participants in July 2022. More details at clinicaltrials.gov (There had been a temporary clinical hold on studies with this drug, but it was lifted in April 2022.)
Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Adults with these cancers are eligible for a randomized, open-label, phase 3 trial comparing the investigational noncovalent Bruton tyrosine-kinase (BTK) inhibitor pirtobrutinib (from Eli Lilly) to current standard ibrutinib (Imbruvica). As with ibrutinib and the earlier BTK inhibitors, mutations at ibrutinib’s binding site, Cys-481, lead to drug resistance in many patients. By contrast, third-generation pirtobrutinib does not bind to Cys-481. It is hoped that this will lead to less drug resistance. Individuals in the study will take once-daily oral pirtobrutinib or ibrutinib for up to approximately 6 years or until discontinuation due to toxicity, arrhythmia, disease progression, or death, whichever occurs first. The study opened in July 2022 at 37 sites in 10 US states and nine countries. It aims to recruit 650 participants. The primary outcome measure is overall response rate (ORR). OS and QoL will not be measured. More details at clinicaltrials.gov
Relapsed/refractory follicular lymphoma (FL). Individuals in this clinical situation can join an open-label, randomized, phase 3 study testing the CAR T-cell therapy axicabtagene ciloleucel (Yescarta) against standard of care. People in the experimental group will receive IV cyclophosphamide and fludarabine for 3 days followed by a single infusion of the cell therapy, which involves patients’ own T-cells being engineered to express receptors keyed to their tumor antigen-mutation profiles. Patients will be followed for 15–20 years. For up to 5 years, individuals in the comparator group will receive a regimen grounded by rituximab (Rituxan) based on investigator’s choice. Sites in Colorado, Massachusetts, New York, Pennsylvania, South Dakota, Tennessee, and Texas opened their doors in September 2022, seeking 230 participants. PFS is the primary outcome; OS and QoL are secondary outcomes. More details at clinicaltrials.gov
Relapsed/refractory follicular lymphoma (FL). People with this type of lymphoma are also eligible to participate in an open-label, randomized, phase 3 trial to see whether disease progression can be safely slowed by the investigational IgG1-bispecific antibody epcoritamab (developed by AbbVie/Genmab), which is designed to bring together cytotoxic T cells and pathogenic CD20+ B cells. All participants will receive lenalidomide plus rituximab (R2) in a 1-year regimen that involves daily tablets of lenalidomide 3 weeks out of 4, plus rituximab infusions once weekly for the first 28-day cycle, then once per cycle for a further four cycles. Two of the three groups of participants will also receive SC injections of epcoritamab at two doses. Centers in Europe, Israel, and South Korea started recruiting for the trial’s 642 participants in September 2022; 37 centers are gearing up across the US. The primary outcome is PFS over approximately 5 years. OS is a secondary endpoint, and QoL will not be tracked. More details at clinicaltrials.gov (Epcoritamab is awaiting approval from the US Food and Drug Administration for use in relapsed/refractory large B-cell lymphoma and was granted a priority review of this application in November 2022.)
Relapsed/refractory mantle cell lymphoma (MCL), Richter’s transformation lymphoma (RTL), follicular lymphoma (FL), or chronic lymphocytic leukemia (CLL). Patients facing one of these clinical scenarios can join an open-label phase 2 trial of zilovertamab vedotin (from Merck Sharp & Dohme). Zilovertamab is an investigational antibody-drug conjugate that targets receptor tyrosine kinase‒like orphan receptor 1 (ROR1). This receptor drives embryonic stem-cell proliferation and later reappears in some cancer cells, endowing them with increased survival and migration, thereby leading to a poor outcome for patients. All participants will receive infusions of zilovertamab every 3 weeks until discontinuation or disease progression for a maximum of 57 weeks. People with MCL who have not previously received noncovalent BTK inhibitors will also receive daily oral nemtabrutinib, Merck’s third-generation BTK inhibitor. Patients with FL or CLL may be given two infusions of zilovertamab during each 3-week cycle instead of one, at slightly lower doses. Sites in Illinois, Kentucky, and Washington and 12 countries other than the US began recruiting the planned 275 trial participants in July 2022. The outcomes are toxicity and objective clinical-response parameters. OS and QoL are not being assessed. More details at clinicaltrials.gov
Relapsed/refractory rare B-cell malignancies. Adult patients with Waldenstrom macroglobulinemia, Richter transformation, Burkitt lymphoma, or hairy cell leukemia whose condition has not responded to treatment or who have experienced relapsed can participate in an open-label, phase 2 study that seeks a clinical response from brexucabtagene autoleucel (Tecartus). This CAR T-cell therapy is already approved for relapsed/refractory disease in MCL and B-cell precursor acute lymphoblastic leukemia, so this trial could pave the way for new indications. All participants will receive a 3-day priming regimen of IV fludarabine and cyclophosphamide, then a single infusion of the CAR-T therapy. Colorado Blood Cancer Institute in Denver and Tennessee Oncology in Nashville started recruiting 170 participants in November 2022. The primary outcomes are various objective response measures, dependant on the disease. OS and QoL are secondary measures. More details at clinicaltrials.gov
All trial information is from the National Institutes of Health US National Library of Medicine (online at clinicaltrials.gov).
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