DS-3201b is an experimental drug that is being investigated in clinical research. Adults with non-Hodgkin lymphoma (NHL) may be able to join this study if their disease has come back after remission or is not responding to current treatment This study has three parts. The Dose Escalation part is designed is to find the safe dose of DS-3201b that adults with advanced NHL can tolerate. The Dose Expansion phase will determine how effective DS-3201b is for rare types of NH and collect additional safety data. Last, the Drug-Drug Interaction (DDI) Cohort (US Only) will evaluate the effect of DS-3201b on the pharmacokinetics (PK) of midazolam and digoxin when co-administered to patients with NHL
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
100
DS-3201 to be administered orally once daily in each 28-day cycle.
DS-3201 to be administered orally once daily in each 28-day cycle at the recommended dose for expansion.
City of Hope National Medical center
Duarte, California, United States
Yale University
New Haven, Connecticut, United States
Emory University
Atlanta, Georgia, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Hackensack University Medical Center
Hackensack, New Jersey, United States
Weill Cornell Medicine
New York, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Duke University Medical Center
Durham, North Carolina, United States
The Ohio State University Wexner Medical Center and James Cancer Hospital
Columbus, Ohio, United States
Thomas Jefferson University
Philadelphia, Pennsylvania, United States
...and 10 more locations
Dose Escalation Period: Number of participants with dose-limiting toxicities (DLTs)
Number of DLT-evaluable participants with protocol-defined DLTs
Time frame: within 28 days after the initial dose of the study drug
Dose Escalation Period: Maximum concentration (Cmax) of DS-3201
Categories: Cycle 1 Day 1, Cycle 1 Day 15
Time frame: within the first 28-day cycle
Dose Escalation Period: Time of maximum concentration (Tmax) of DS-3201
Categories: Cycle 1 Day 1, Cycle 1 Day 15
Time frame: within the first 28-day cycle
Dose Escalation Period: Area under the plasma concentration time curve up to the last quantifiable time (AUClast) for DS-3201
Time frame: Day 1 of the first 28-day cycle
Dose Escalation Period: Area under the plasma concentration time curve during the dosing interval (AUCtau) for DS-3201
Time frame: Day 1 of the first 28-day cycle
Dose Escalation Period: Trough (minimum) plasma concentration (Ctrough)
Time frame: Day 15 of the first 28-day cycle
Dose Escalation Period: Average plasma concentration (Cavg)
Time frame: Day 15 of the first 28-day cycle
DDI cohort only: Maximum concentration (Cmax) of DS-3201, midazolam, digoxin
Categories: Day -4, Cycle 1 Day 1, Cycle 1 Day 15
Time frame: within the first 28-day cycle
DDI cohort only: Time of maximum concentration (Tmax) of DS-3201, midazolam, digoxin
Categories: Day -4, Day 0 (for alternate schedule), Cycle 1 Day 1, Cycle 1 Day 15
Time frame: within the first 28-day cycle
DDI cohort only: Area under the plasma concentration time curve up to the last quantifiable time (AUClast) for DS-3201,midazolam,digoxin
Categories: Day -4, Day 0 (for alternate schedule), Cycle 1 Day 1, Cycle 1 Day 15
Time frame: within the first 28-day cycle
DDI cohort only: Area under the plasma concentration time curve during the dosing interval (AUCtau) for DS-3201, midazolam, digoxin
Cycle 1 Day 1, Cycle 1 Day 15
Time frame: within the first 28-day cycle
Number of participants with treatment-emergent adverse events (TEAEs)
TEAEs are systematically collected from lab values, physical exams, and other investigations
Time frame: through the end of the study (within approximately 5 years)
Best overall response, based on international consensus criteria
Best overall response is defined as the percentage of participants who achieved each category as the best response, considering all overall responses assessed at all time points after the start of study treatment. Categories: CR, CRu, PR, SD, RD/PD, UA Categories: Malignant lymphoma, ATL, CTCL
Time frame: from the start of study treatment to the end of follow-up visit (within 5 years)
Objective response rate (ORR)
ORR is defined as the percentage of participants who were assessed for best overall response, who achieved CR, CRu, or PR
Time frame: within 5 years
Disease control rate (DCR)
DCR is defined as the percentage of participants who were assessed for best overall response, who achieved a best response of CR, CRu, PR, or SD
Time frame: within 5 years
Duration of response (DOR)
DOR is defined as the time from the date at which criteria are first met for CR or PR (including CRu for ATL) until the first date that progressive disease is objectively documented.
Time frame: within 5 years
Progression-free survival (PFS)
PFS is defined as the time from the date of the first dose to the earlier of the dates of the first objective documentation of disease progression or death due to any cause.
Time frame: witihn 5 years
Number of participants with malignant lymphoma who achieved each level of therapeutic response per international consensus standards
Categories: Complete remission (CR), Partial remission (PR), Stable disease (SD), Relapsed disease or progressive disease (RD/PD)
Time frame: through the end of the study (within approximately 5 years)
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