Phase 1 Study Evaluates Venetoclax/Lenalidomide/Rituximab in Newly-Diagnosed MCL

Tycel Jovelle Phillips, MD, a clinical associate professor of hematology, medical oncology, and internal medicine, at University of Michigan Health, discusses the design of a phase 1 study (NCT03523975) looking at venetoclax (Venclexta), lenalidomide (Revlimid), and rituximab (Rituxan) in patients with newly diagnosed mantle cell lymphoma (MCL).

According to Philips, the study was open to a large patient population. Any patient who was newly diagnosed, regardless of transplant eligibility or high-risk features were eligible to participate. The goal was to utilize the triplet combination the same way cytotoxic chemotherapy would be used. 

Patients were given a 12-month induction of lenalidomide plus venetoclax. Venetoclax was escalated weekly until the maximum dose of 400 milligrams was reached. Response assessments were conducted every 3 moths. Patients were able to transfer over to maintenance after cycles 6, 9, or 12. Each drug was stopped sequentially over the course of several years.

0:08 | We did not want to cherry pick the patients in a sense. So, we opened up the study to a very broad enrollment. We wanted to sort of utilize this as we would utilize cytotoxic chemotherapy. So, all the patients who were newly diagnosed were considered to be eligible for the study irrespective of whether we thought they were transplant eligible or ineligible. We didn't exclude any high-risk features or cytogenetic abnormalities.

0:33 | And how we originally designed this study, we designed it very similarly to the Cornell group. So, the plan was to give a 12-month induction of lenalidomide plus venetoclax. We started the venetoclax on day 8, but 50 milligrams of the plan escalated up weekly, until we reached a maximum dose of 400 milligrams. So, we had a very prolonged DLT period of about 42 days because of the escalation. Thereafter, the plan was to have response assessments every 3 months by radiographs and also MRD testing. The plan was to continue that for a year, because very early on in the study we saw several patients have a very early MRD undetectable result and radiographic response within the first 3 to 6 months. The plan was to modify the protocol so that after 6 months the patients who were MRD undetectable and also in a radiographic remission, they can transition over to maintenance. Maintenance was after cycle 6, 9 or 12. The patients would reduce the dose of lenalidomide by half and then continue on with the other 2 agents of venetoclax and rituximab. And we plan this treatment regimen to sequentially stop. So, the venetoclax would continue for a year of only in maintenance. The lenalidomide would be continued for 2 years and maintenance and then the rituximab we consider for 3. So, every year the patients would stop a treatment eventually they will be off all therapy.