A Phase I/II Dose-Escalation and Expansion Study Of The Selective PKC-Β Inhibitor MS-553 In Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
60
Oral, multiple dose levels
Oral recommended phase 2 dose of MS-553
Oral
University Of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States
Columbia University, Herbert Irving Comprehensive Cancer Center
New York, New York, United States
The Ohio State University, James Comprehensive Cancer Center
Columbus, Ohio, United States
MD Anderson Cancer Center, Department of Leukemia
Houston, Texas, United States
The Incidence Rate of DLT and TEAE Requiring Study Drug Discontinuation
DLT are defined as any of the following treatment-emergent events occurring during the DLT evaluation period. 1. Death 2. Hematologic toxicities: • Grade 4 neutropenia for ≥ 7 days • Grade 3 febrile neutropenia: absolute neutrophil count (ANC) 38.3°C (101°F) or a sustained temperature ≥38°C (100.4°F) for \> 1 hour • Grade 4 thrombocytopenia ≥ 14 days (patients with baseline platelet count of ≥ 50 x 109 /L) • Grade 4 thrombocytopenia ≥ 28 days (patients with baseline platelet count \< 50 x 10 9 /L) • ≥ Grade 3 thrombocytopenia associated with ≥ Grade 2 hemorrhage • New ≥ Grade 3 anemia requiring transfusion in a patient previously transfusion independent. 3. Nonhematologic toxicities: • Any other ≥ Grade 3 toxicity not reversed to any one of the following three conditions in 7 days with appropriate intervention: a) baseline; b) \< Grade 1; or c) a status considered to be controlled by the SRC. • Any TEAE requiring \>25% of doses of scheduled study drug to be withheld during the DLT period
Time frame: Assessments for DLT and TEAE will occur during Cycle 1 (28 days) for A1 Cohort and B1 Cohort and Cycles 1-4 (up to 112 days) for C1 Cohort.
The ORR of MS-553 in Patients With CLL/SLL Whose Disease Relapsed After or Was Refractory to at Least One Prior Therapy
This will be assessed according to the 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Response Criteria with modifications for treatment-related lymphocytosis. Any patient who receives at least one cycle of study therapy is evaluable for response.
Time frame: Evaluation of the efficacy endpoints related to response will incorporate the data from the first 9 cycles (up to 252 days) of treatment.
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Oral
IV
IV
Huntsman Cancer Institute
Salt Lake City, Utah, United States