This multicenter, multi-arm trial evaluated the safety and efficacy of tagraxofusp, a cell division cycle protein 123 homolog-targeted therapy, in participants with either CMML or MF. There were 2 CMML cohorts, 1 enrolled participant with CMML (CMML-1 or CMML-2) who were refractory/resistant or intolerant to hypomethylating agents (HMA), hydroxyurea (HU), or intensive chemotherapy and 1 enrolled treatment-naive participants with CMML (CMML-1 or CMML-2) with molecular features associated with poor prognosis. The MF cohort enrolled participants who were resistant/refractory or intolerant to approved Janus kinase (JAK) therapy (JAK1/JAK2 or JAK2).
This was a non-randomized, open-label, multicenter study, divided into 3 stages. Stage 1: Stage 1 of the study was to enroll participants with CMML, MF, advanced systemic mastocytosis, or advanced symptomatic primary eosinophilic disorder. Stage 2: Stage 2 was to enroll MF and CMML participants. Stage 3A: Stage 3A was to enroll 2 populations of participants with CMML, those with CMML-1 or CMML-2 who were refractory/resistant/intolerant to HMAs, HU, or intensive chemotherapy (relapsed/refractory participants); and participants with treatment-naïve CMML-1 or CMML-2 (previously untreated participants) with molecular features associated with a poor prognosis.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
82
Tagraxofusp was administered as a 15-minute intravenous infusion once daily for the first 3 consecutive days of each dosing cycle.
University of California, San Francisco
Clovis, California, United States
City of Hope
Duarte, California, United States
University of California, Los Angeles
Los Angeles, California, United States
Stanford Cancer Institute
Stanford, California, United States
Mayo Clinic Florida
Jacksonville, Florida, United States
Georgia Cancer Center at Augusta University
Augusta, Georgia, United States
Rush University Medical Center
Chicago, Illinois, United States
Indiana Blood and Bone Marrow Transplantation
Indianapolis, Indiana, United States
University of Kansas Cancer Center
Westwood, Kansas, United States
Norton Cancer Institute
Louisville, Kentucky, United States
...and 14 more locations
Number of Participants With Dose-limiting Toxicities (DLTs)
During Stage 1, DLT was defined as any of the following occurring during the first cycle of therapy: any treatment-emergent Grade 4 transaminase or creatine phosphokinase (CPK) elevation (confirmed within 24 hours of initial identification), regardless of duration or relationship to SL-401; any Grade ≥3 non-hematologic toxicity (unrelated to underlying MPN), with the exception of Grade 3 laboratory toxicities that resolve to Grade ≤1 or baseline ≤28 days after the last infusion of SL-401, or the following Grade 3 toxicities if they resolve to Grade ≤1 or baseline ≤21 days after the last infusion of SL-401, arthralgia, myalgia, fever responding to treatment, nausea and/or vomiting (excluding cases that require tube feeding, total parenteral nutrition, or hospitalization) or diarrhea associated with suboptimal prophylaxis or treatment; Grade 4 neutropenia or Grade 4 thrombocytopenia with a duration (at Grade 4) of ≥28 days.
Time frame: 21 days of Cycle 1 (21 days/cycle)
Objective Response Rate (ORR)
ORR was defined as the percentage of participants (responders) who achieved disease-specific complete response (CR) or partial response (PR) after treatment. For response assessment of myelofibrosis during both Stage 1 and Stage 2, the International Working Group-Myeloproliferative Neoplasms Research and Treatment and European LeukemiaNet (IWG-MRT/ELN 2013) criteria were used. For chronic myelomonocytic leukemia, during both Stage 1 and Stage 2, the International Working Group 2006 response criteria for myelodysplastic syndromes (IWG MDS 2006) were used for response assessment while the Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN) 2015 criteria were used for response assessment during Stage 3A.
Time frame: 1145 days
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