Safety and Efficacy of Entospletinib With Vincristine and Dexamethasone in Adults With Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL)

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

A Phase 1b/2, Open-Label, Dose Escalation and Expansion Study Evaluating the Safety and Efficacy of Entospletinib (GS-9973) With Vincristine and Dexamethasone in Adult Subjects With Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02404220
• Other study ID #: GS-US-339-1560
• Secondary ID: 2015-002768-18
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: May 6, 2015
• Est. completion date: December 17, 2018

Study information

• Verified date: December 2019
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 30
• Est. completion date: December 17, 2018
• Est. primary completion date: November 16, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Adults with ALL in need of treatment

Key Exclusion Criteria:

• Diagnosis of Burkitt's Leukemia, or lymphoid blast crisis of chronic myelogenous leukemia (CML)

• History of myelodysplastic syndrome or solid organ transplantation

• Prior allogeneic bone marrow progenitor cell transplant within 100 days or on active immunosuppression for graft versus host disease (GVHD) treatment or prophylaxis within 28 days prior to enrollment

Note: Other protocol defined Inclusion/ Exclusion criteria may apply.

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• Entospletinib

• Vincristine

• Dexamethasone

• CNS Prophylaxis

Locations

Country	Name	City	State
Canada	Princess Margaret	Toronto	Ontario
Germany	Medizinische Klinik mit Schwerpunkt Hepatologie & Gastroenterology	Berlin
Germany	Medizinische Klinik und Poliklinik I	Wurzburg
United States	University of Chicago	Chicago	Illinois
United States	The Ohio State University	Columbus	Ohio
United States	City of Hope	Duarte	California
United States	Bon Secour St. Francis Hospital	Greenville	South Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	UCLA	Los Angeles	California
United States	Memorial Sloan-Kettering	New York	New York
United States	UC Irvine Medical Center	Orange	California
United States	University of California San Diego (UCSD)	San Diego	California
United States	University of WA	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Canada,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	ENTO Lead-in and Cycle 1 (Day -7 through Day 28)
Secondary	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.	End of Induction (Cycle 2, Day 28)
Secondary	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	End of Induction (Cycle 2, Day 28)
Secondary	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.	End of Induction (Cycle 2, Day 28)
Secondary	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	End of Induction (Cycle 2, Day 28)