The primary objective of this study is to evaluate the safety of entospletinib in combination with vincristine (VCR), and dexamethasone (DEX) in adults with previously treated relapsed or refractory B-cell lineage acute lymphoblastic leukemia (ALL). This is a dose escalation study in which after 2 induction cycles participants may be put on maintenance for up to 36 cycles if they have obtained clinical benefit from the treatment.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
30
City of Hope
Duarte, California, United States
UCLA
Los Angeles, California, United States
UC Irvine Medical Center
Orange, California, United States
Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs)
The occurrence of any of the following toxicities during Lead-in/Cycle 1 (Day -7 through Day 28) was considered a DLT if judged by the investigator to be possibly, probably, or definitely related to the administration of any drug in the treatment regimen (ENTO, VCR, DEX, institutional standard CNS prophylaxis): * Grade 4 (or higher) non-hematologic toxicity * Grade 3 non-hematologic toxicity lasting ≥ 7 days despite optimal supportive care * Any Grade 3 non-hematologic laboratory value if: * Medical intervention was required to treat, or * The abnormality led to hospitalization, or * The abnormality persisted for \> 1 week * Grade 4 Neutropenia (absolute neutrophil count \[ANC\] \< 500 /μL) persistent for greater than 14 days or associated with febrile neutropenia * Grade 4 thrombocytopenia (platelets \< 25,000/μL) persisting for greater than 14 days (or greater than 25,000 /μL, but requiring prophylactic platelet transfusion to maintain this level)
Time frame: ENTO Lead-in and Cycle 1 (Day -7 through Day 28)
Percentage of Participants With Complete Remission (CR) at the End of Induction
Assessment of clinical response was made according to National Comprehensive Cancer Network (NCCN) guidelines on acute lymphoblastic leukemia (ALL) Version 2, 2016. CR required all of the following: * No circulating blasts or extramedullary disease (no lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement). * Trilineage hematopoiesis (TLH) and \< 5% blasts in bone marrow aspirate. * ANC \> 1000/μL. * Platelets \> 100,000/μL.
Time frame: End of Induction (Cycle 2, Day 28)
Percentage of Participants With Overall Remission at the End of Induction
Assessment of clinical response was made according to NCCN guidelines on ALL Version 2, 2016. Overall remission included CR and complete remission with incomplete hematologic recovery (CRi). CR required all of the following: * No circulating blasts or extramedullary disease (no lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement). * TLH and \< 5% blasts in bone marrow aspirate. * ANC \> 1000/μL. * Platelets \> 100,000/μL. CRi required all criteria for CR except platelet count and/or ANC: * Platelets ≤ 100,000/μL and/or ANC is ≤ 1000/μL
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University of California San Diego (UCSD)
San Diego, California, United States
University of Chicago
Chicago, Illinois, United States
Hackensack University Medical Center
Hackensack, New Jersey, United States
Memorial Sloan-Kettering
New York, New York, United States
The Ohio State University
Columbus, Ohio, United States
Bon Secour St. Francis Hospital
Greenville, South Carolina, United States
University of WA
Seattle, Washington, United States
...and 3 more locations
Time frame: End of Induction (Cycle 2, Day 28)
Percentage of Participants With Partial Response (PR) at the End of Induction
PR required all of the following: * No circulating blasts or extramedullary disease (no lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement). * TLH and bone marrow may contain ≥ 5% but less than 25% blast morphology. * ANC \> 1000/μL. * Platelets \> 100,000/μL.
Time frame: End of Induction (Cycle 2, Day 28)
Percentage of Participants With Overall Response at the End of Induction
Overall response included CR, CRi, and PR. CR required all of the following: * No circulating blasts or extramedullary disease (no lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement). * TLH and \< 5% blasts in bone marrow aspirate. * ANC \> 1000/μL. * Platelets \> 100,000/μL. CRi required all criteria for CR except platelet count and/or ANC: * Platelets ≤ 100,000/μL and/or ANC is ≤ 1000/μL PR required all criteria for CR except for bone marrow blasts: * bone marrow may contain ≥ 5% but less than 25% blast morphology
Time frame: End of Induction (Cycle 2, Day 28)