Abstract CT145: The final results of a phase I study using velcade (bortezomib), cladribine, and rituximab (VCR) in treating elderly patient with mantle cell lymphoma
Authors: Pu Jeffrey J. , Berger Kristin , Claxton David , Drabick Joseph , Loughran Thomas , Epner Elliot 
Published: April 2024

Abstract
Background: Mantle cell lymphoma (MCL) is a moderately aggressive and incurable small to medium size B cell lymphoma. In this phase 1 study, we evaluated the safety and efficiency of Valcade, Cladribine, and Rituximab (VCR) combination treatment in MCL.
Patients and Methods: This is a single arm, open label, investigator-initiated Phase 1 study. This study employed a standard 3+3 dose escalation scheme designed to determine the maximum tolerated dose (MTD) of Cladribine in VCR regimen. The treatment scheme and Cladribine dose escalation levels (1, 2, and 3) are as follows: the therapy consisted of 6 28-day cycles. At first cycle of the treatment, Rituximab 375 mg/m2 infusion started on day 5 of the first week and then given weekly for 3 weeks; in the next 5 cycles, Rituximab was given on day 5 of each cycle, and then every 2 months as the maintenance therapy. Cladribine 35 mg/m2 (3 mg/m2 for level 1, 4 mg/m2 for level 2, and 5 mg/m2 for level 3) infusion was given on days 1 to 5 for 6 cycles. If the patient was older than 70 years old, Cladribine was only given on days 1 to 3 of each cycle. Velcade 1.6 mg/m2 subcutaneous injection was given on days 12, 19 and 26 for cycles 1 to 3, then Day 5 and 19 during Cycles 4 to 6, then once per month as maintenance therapy until toxicity or progression of the disease. The primary endpoint of this study was to investigate the dose limiting toxicity (DLT), safety, and efficiency of this regimen in patients with MCL. The secondary endpoints included remission rate (RR), progression free survival (PFS) and overall survival (OS). This study is registered with clinicaltrials.gov (NCT01439750).
Results: No subject experienced dose limited toxicity (DLT) at either level 1 or 2, one possible DLT (infectious colitis) was observed on a subject during 2nd cycle at level 3. Then no additional DLTs were seen in 3 subjects added to level 3. Overall, this study recruited 13 subjects, with a median age of 64 years old (range from 55 to 83), and a total of 11 male and 2 females. Ten subjects were never previously treated, while 3 either relapsed or failed previous treatments. The majority of subjects tolerated this regimen well. Two relapsed patients experienced disease progression after received two cycles of treatments and died in 5 and 7 months after initiating the treatment. Another patient died 15 months after starting treatment. The overall remission (OR) rate was 77% (10/13) and complete remission (CR) rate was 85% (10/13). In newly diagnosed subject cohort, the RR and OS rates were 90% (9/10), PFR was 80% (8/10), and CR rate was 100% (10/10), of which 3 patients have been followed for more than 4 years, 3 other patients for more than 3 years, and 3 others for over 2 years. However, in relapsed/refractory subject cohort, 1 subject achieved CR for 7 months but then relapsed, 2 subjects had no response. There were 2 blastoid subjects, one was newly diagnosed and achieved CR.No severe systemic toxicity was observed in this study. Bone marrow suppression caused prolonged anemia and thrombocytopenia were the most common toxicity (3/13 with ≤grade 2). Low grade peripheral neuropathies (≤grade 2) were observed in 15% (2/13). Mild fatigue was a frequent complaint.
Conclusions: The VCR combination is a well-tolerated, low toxicity and effective regimen for for untreated MCL. Cladribine 5 mg/m2 is a tolerable dose with manageable toxicity.
Citation Format: Jeffrey J. Pu, Kristin Berger, David Claxton, Joseph Drabick, Thomas Loughran, Elliot Epner. The final results of a phase I study using velcade (bortezomib), cladribine, and rituximab (VCR) in treating elderly patient with mantle cell lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT145.