Entospletinib Monotherapy and in Combination With Chemotherapy in Adults With Acute Myeloid Leukemia (AML) (ENTO in AML)
Acute Myeloid Leukemia
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia
Eligibility Criteria
Key Inclusion Criteria:
- Adults with AML in need of treatment
- Group A : Individuals ≥ 18 years of age with previously untreated AML by World Health Organization (WHO) criteria who are able and should receive up to 2 cycles of induction chemotherapy with 7+3 as determined by the treating physician
- Group B: Individuals > 70 years of age with previously untreated AML by WHO criteria; or individuals ≤ 70 years of age with previously untreated AML who refuse or are unable to receive chemotherapy with 7+3 as determined by the treating physician
- Group C: Individuals ≥ 18 years of age with relapsed/refractory AML by WHO criteria; or with relapsed/refractory AML with mixed-lineage leukemia (MLL); or with previously untreated AML by WHO criteria and who would have met disease eligibility criteria for Group A or B but refuse or are unable to receive chemotherapy and hypomethylating agent as determined by the treating physician
Key Exclusion Criteria:
- Known active central nervous system or leptomeningeal lymphoma
- Subjects with acute promyelocytic leukemia (M3)
- Treatment with proton pump inhibitors (PPIs) within 7 days prior to enrollment.
NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.
Sites / Locations
- UCLA
- University of Chicago
- Loyola University Medical Center
- Indiana University
- University of Kansas Medical Center Research Institute, Inc
- Dana Farber Cancer Institute
- Henry Ford Health System
- Karmanos Cancer Institute
- Weill Cornell Medical College - New York - Presbyterian Hospital
- Duke Cancer Center
- University Hospitals Case Medical Center
- Ohio State University
- Oregon Health & Science University
- Saint Francis Cancer Center
- Princess Margaret
- Jewish General Hospital
- Universitätsklinikum Frankfurt Medizinische Klinik II
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Entospletinib + daunorubicin + cytarabine (Group A)
Entospletinib + decitabine (Group B)
Entospletinib (Group C)
Dose Escalation: Entospletinib up to 400 mg for 14 days and then entospletinib up to 400 mg in combination with daunorubicin and cytarabine for up to two 14-day cycles. Dose Expansion: Entospletinib 400 mg for 14 days and then entospletinib 400 mg in combination with daunorubicin and cytarabine for up to two 14-day cycles. Some participants will have the option to receive post-induction therapy with entospletinib 400 mg in combination with cytarabine/cytosine arabinoside (ARA-C). Participants may receive maintenance therapy with 28-day cycles of entospletinib 400 mg for up to twelve 28-day cycles, if the participant is not eligible for stem cell transplant.
Dose Escalation: Entospletinib 400 mg for 14 days and then entospletinib 400 mg in combination with decitabine for 10 days beginning on Day 1 of every 28-day cycle (at least 2 cycles of induction therapy but no more than 4 cycles). Participants who are intolerant of decitabine may switch to entospletinib monotherapy maintenance at any time after completing the first 2 cycles. Dose Expansion: Entospletinib 400 mg for 14 days for the safety run-in participants or Entospletinib 400 mg for 5 days for the randomization participants. Then entospletinib 400 mg in combination with decitabine or azacitidine (at least 2 cycles of induction therapy but no more than 4 cycles). Some participants will have the option to receive maintenance therapy with entospletinib in combination with decitabine or azacitidine. Participants who are intolerant of decitabine or azacitidine may switch to entospletinib monotherapy maintenance at any time after completing the first 2 cycles.
Dose Escalation: Entospletinib up to 800 mg for 28-day cycles until the participant meets criteria for study treatment discontinuation per the study protocol. Dose Expansion: Entospletinib 400 mg for 28-day cycles until the participant meets criteria for study treatment discontinuation per the protocol.