PMID- 35641232
OWN - NLM
STAT- MEDLINE
DCOM- 20220707
LR  - 20220919
IS  - 1549-490X (Electronic)
IS  - 1083-7159 (Print)
IS  - 1083-7159 (Linking)
VI  - 27
IP  - 7
DP  - 2022 Jul 5
TI  - Vincristine Sulfate Liposome Injection with Bendamustine and Rituximab as 
      First-Line Therapy for B-Cell Lymphomas: A Phase I Study.
PG  - 532-e542
LID - 10.1093/oncolo/oyab079 [doi]
AB  - BACKGROUND: We conducted an investigator-initiated, phase I trial of vincristine 
      sulfate liposomal injection (VSLI) in combination with bendamustine and rituximab 
      (BR) for indolent B-cell (BCL) or mantle cell lymphoma. METHODS: Participants 
      received 6 cycles of standard BR with VSLI at patient-specific dose determined by 
      the Escalation with Overdose Control (EWOC) model targeting 33% probability of 
      dose-limiting toxicity (DLT). Maximum tolerated dose (MTD) was the primary 
      endpoint; secondary endpoints included rates of adverse events (AEs), overall 
      response rate (ORR), and complete response (CR). Vincristine sulfate liposomal 
      injection is FDA approved for the treatment of patients with recurrent 
      Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL). 
      RESULTS: Among 10 enrolled patients, VSLI was escalated from 1.80 to 2.24 mg/m2, 
      with one DLT (ileus) at 2.04 mg/m2. Two patients discontinued VSLI early. The 
      most common AE included lymphopenia (100%), constipation, nausea, infusion 
      reaction (each 60%), neutropenia, and peripheral neuropathy (50%). Grade 3/4 AE 
      included lymphopenia (90%), neutropenia (20%), and ileus (10%), with prolonged 
      grade >/=2 lymphopenia observed in most patients. Calculated MTD for VSLI was 
      2.25 mg/m2 (95% Bayesian credible interval: 2.00-2.40). Overall response was 100% 
      with 50% CR. With median follow-up 26 months, 4/10 patients experienced 
      recurrence and 1 died. CONCLUSION: Vincristine sulfate liposomal injection at 
      2.25 mg/m2 can be safely combined with BR for indolent B-cell lymphoma, but given 
      observed toxicities and recurrences, we did not pursue an expanded 
      cohort.Clinical Trials Registration Number: ClinicalTrials.gov identifier 
      NCT02257242.
CI  - (c) The Author(s) 2022. Published by Oxford University Press.
FAU - Ollila, Thomas
AU  - Ollila T
AD  - Department of Medicine, Alpert Medical School of Brown University, Providence, 
      RI, USA.
AD  - Division of Hematology-Oncology, Rhode Island Hospital, Providence, RI, USA.
FAU - Butera, James
AU  - Butera J
AD  - Department of Medicine, Alpert Medical School of Brown University, Providence, 
      RI, USA.
AD  - Division of Hematology-Oncology, Rhode Island Hospital, Providence, RI, USA.
FAU - Egan, Pamela
AU  - Egan P
AD  - Department of Medicine, Alpert Medical School of Brown University, Providence, 
      RI, USA.
AD  - Division of Hematology-Oncology, Rhode Island Hospital, Providence, RI, USA.
FAU - Reagan, John
AU  - Reagan J
AD  - Department of Medicine, Alpert Medical School of Brown University, Providence, 
      RI, USA.
AD  - Division of Hematology-Oncology, Rhode Island Hospital, Providence, RI, USA.
FAU - Thomas, Anthony
AU  - Thomas A
AD  - Department of Medicine, Alpert Medical School of Brown University, Providence, 
      RI, USA.
AD  - Division of Hematology-Oncology, Rhode Island Hospital, Providence, RI, USA.
FAU - Yakirevich, Inna
AU  - Yakirevich I
AD  - Division of Hematology-Oncology, Rhode Island Hospital, Providence, RI, USA.
FAU - MacKinnon, Kelsey
AU  - MacKinnon K
AD  - Brown University Oncology Research Group (BrUOG), Providence, RI, USA.
FAU - Margolis, Jeannine
AU  - Margolis J
AD  - Brown University Oncology Research Group (BrUOG), Providence, RI, USA.
FAU - McMahon, Jessica
AU  - McMahon J
AD  - Lifespan Oncology Clinical Research, Providence, RI, USA.
FAU - Rosati, Valerie
AU  - Rosati V
AD  - Lifespan Oncology Clinical Research, Providence, RI, USA.
FAU - Olszewski, Adam J
AU  - Olszewski AJ
AUID- ORCID: 0000-0002-6472-6658
AD  - Department of Medicine, Alpert Medical School of Brown University, Providence, 
      RI, USA.
AD  - Division of Hematology-Oncology, Rhode Island Hospital, Providence, RI, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT02257242
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncologist
JT  - The oncologist
JID - 9607837
RN  - 0 (Liposomes)
RN  - 4F4X42SYQ6 (Rituximab)
RN  - 5J49Q6B70F (Vincristine)
RN  - 981Y8SX18M (Bendamustine Hydrochloride)
SB  - IM
MH  - Adult
MH  - *Antineoplastic Combined Chemotherapy Protocols/adverse effects
MH  - Bayes Theorem
MH  - Bendamustine Hydrochloride/therapeutic use
MH  - Humans
MH  - Ileus/chemically induced
MH  - Liposomes
MH  - *Lymphoma, B-Cell/drug therapy
MH  - Lymphopenia
MH  - Neutropenia/chemically induced
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy
MH  - Rituximab/therapeutic use
MH  - Vincristine/therapeutic use
PMC - PMC9255974
OTO - NOTNLM
OT  - B-cell lymphoma
OT  - bendamustine
OT  - phase I
OT  - rituximab
OT  - vincristine sulfate liposome injection
EDAT- 2022/06/01 06:00
MHDA- 2022/07/08 06:00
PMCR- 2022/03/07
CRDT- 2022/05/31 21:25
PHST- 2021/10/25 00:00 [received]
PHST- 2021/12/06 00:00 [accepted]
PHST- 2022/06/01 06:00 [pubmed]
PHST- 2022/07/08 06:00 [medline]
PHST- 2022/05/31 21:25 [entrez]
PHST- 2022/03/07 00:00 [pmc-release]
AID - 6543668 [pii]
AID - oyab079 [pii]
AID - 10.1093/oncolo/oyab079 [doi]
PST - ppublish
SO  - Oncologist. 2022 Jul 5;27(7):532-e542. doi: 10.1093/oncolo/oyab079.