DS-3201b in Participants With Lymphomas
- Conditions
- Lymphoma, MalignantNon-hodgkin Lymphoma
- Interventions
- Registration Number
- NCT02732275
- Lead Sponsor
- Daiichi Sankyo Co., Ltd.
- Brief Summary
DS-3201b is an experimental drug. It is not approved for regular use. It can only be used in clinical research.
Adults with non-Hodgkin lymphoma (NHL) might be able to join this study if their disease:
* has come back after remission
* is not responding to current treatment
This study has three parts:
1. Dose Escalation is to find the safe dose of DS-3201b that adults with advanced NHL can tolerate.
2. Dose Expansion is to:
* find out how effective DS-3201b is for rare types of NHL
* collect additional safety data
3. Drug-Drug Interaction (DDI) Cohort (US Only) is to evaluate the effect of DS-3201b on the pharmacokinetics (PK) midazolam and digoxin when co-administered to patients with NHL
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 100
-
Has hematocytological or pathological diagnosis of non- Hodgkin's lymphoma (NHL)
-
Has relapsed from or is refractory to standard treatment or no standard treatment is available
-
Is the age of majority in their country (18 in the US and 20 in Japan) at the time of informed consent
-
Has Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
-
Has at least one evaluable lesion site (not applicable for the DDI cohort)
-
Has preserved organ function based on baseline laboratory data at screening tests
-
If of reproductive potential, agrees to avoid harvesting ova or sperm, and to use a protocol-defined form of contraception or avoid intercourse, during and upon completion of the study, and for at least 3 months after the last dose of study drug
-
Tumor biopsy collections:
-
willing to provide archived or fresh tumor tissue samples that are sufficient for comprehensive genomic and/or proteomic analyses at baseline
-
[US only] willing to provide fresh on-treatment tumor biopsy if deemed acceptable risk by the investigator
[Japan only] fresh on-treatment tumor biopsy should be performed if deemed acceptable risk by the investigator
-
willing to provide optional fresh end-of-treatment biopsy
-
For ATL subjects:
- Has a positive test result for human T-lymphotropic virus type I antibody
- Has ATL subtype classified as acute, lymphomatous, or chronic with poor prognostic factor
- Has diagnosis of relapse (including relapse after partial remission [PR]) or treatment-resistant ATL at the time of informed consent after prior treatment with at least 1 anti-cancer medication regimen
- Has been diagnosed with protocol-defined cutaneous T-cell lymphoma or T-cell leukemia. For DDI cohort, CTCL is not exclusionary.
- Has a history or presence of central nervous system (CNS) involvement
- Has a medical history, complication or other malignancy considered inappropriate for participation in the study, or a serious physical or psychiatric disease, the risk of which may be increased by participation in the study
- Has received drugs or other treatments not allowed by the protocol
- History of treatment with other enhancer of zeste (EZH) inhibitors
- Has had allogeneic hematopoietic stem cell transplantation (HTCP) within 90 days before scheduled dosing on Cycle 1 Day 1
- Is pregnant or breastfeeding
- Is otherwise deemed ineligible to participate by the investigator or sub-investigator
DDI Cohort Only:
- Has received following medications within 14 days prior to study drug administration
- Any CYP3A inhibitors/inducers including weak CYP3A inhibitors/inducers, and P-gp inhibitors, midazolam as well as digoxin
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Dose Expansion - DS-3201b DS-3201b Part 2 is a dose expansion to examine the safety and efficacy of DS-3201b. Dose Escalation - DS-3201b DS-3201b Dose escalation is to identify the recommended phase 2 dose of DS-3201b guided by the modified continuous reassessment method using a Bayesian logistic regression model following escalation.
- Primary Outcome Measures
Name Time Method Dose Escalation Period: Number of participants with dose-limiting toxicities (DLTs) within 28 days after the initial dose of the study drug Number of DLT-evaluable participants with protocol-defined DLTs
Dose Escalation Period: Maximum concentration (Cmax) of DS-3201 within the first 28-day cycle Categories: Cycle 1 Day 1, Cycle 1 Day 15
Dose Escalation Period: Time of maximum concentration (Tmax) of DS-3201 within the first 28-day cycle Categories: Cycle 1 Day 1, Cycle 1 Day 15
Dose Escalation Period: Area under the plasma concentration time curve up to the last quantifiable time (AUClast) for DS-3201 Day 1 of the first 28-day cycle Dose Escalation Period: Trough (minimum) plasma concentration (Ctrough) Day 15 of the first 28-day cycle Dose Escalation Period: Average plasma concentration (Cavg) Day 15 of 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 within the first 28-day cycle Categories: Day -4, Day 0 (for alternate schedule), Cycle 1 Day 1, Cycle 1 Day 15
Number of participants with treatment-emergent adverse events (TEAEs) through the end of the study (within approximately 5 years) TEAEs are systematically collected from lab values, physical exams, and other investigations
Dose Escalation Period: Area under the plasma concentration time curve during the dosing interval (AUCtau) for DS-3201 Day 1 of the first 28-day cycle DDI cohort only: Maximum concentration (Cmax) of DS-3201, midazolam, digoxin within the first 28-day cycle Categories: Day -4, Cycle 1 Day 1, Cycle 1 Day 15
DDI cohort only: Area under the plasma concentration time curve during the dosing interval (AUCtau) for DS-3201, midazolam, digoxin within the first 28-day cycle Cycle 1 Day 1, Cycle 1 Day 15
DDI cohort only: Time of maximum concentration (Tmax) of DS-3201, midazolam, digoxin within the first 28-day cycle Categories: Day -4, Day 0 (for alternate schedule), Cycle 1 Day 1, Cycle 1 Day 15
- Secondary Outcome Measures
Name Time Method Best overall response, based on international consensus criteria from the start of study treatment to the end of follow-up visit (within 5 years) 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, CTCLObjective response rate (ORR) within 5 years ORR is defined as the percentage of participants who were assessed for best overall response, who achieved CR, CRu, or PR
Disease control rate (DCR) within 5 years 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
Duration of response (DOR) within 5 years 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.
Progression-free survival (PFS) witihn 5 years 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.
Number of participants with malignant lymphoma who achieved each level of therapeutic response per international consensus standards through the end of the study (within approximately 5 years) Categories: Complete remission (CR), Partial remission (PR), Stable disease (SD), Relapsed disease or progressive disease (RD/PD)
Trial Locations
- Locations (20)
The Ohio State University Wexner Medical Center and James Cancer Hospital
🇺🇸Columbus, Ohio, United States
City of Hope National Medical center
🇺🇸Duarte, California, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Weill Cornell Medicine
🇺🇸New York, New York, United States
National Cancer Center Hospital East
🇯🇵Kahiwa-shi, Chiba, Japan
Kumamoto University Hosipital
🇯🇵Kumamoto-shi, Kumamoto, Japan
Iwate Medical University Hospital
🇯🇵Morioka-shi, Iwate, Japan
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Imamura General Hospital
🇯🇵Kagoshima-shi, Kagoshima, Japan
Nagoya City University Hospital
🇯🇵Nagoya-shi, Aichi, Japan
Kagoshima University Hospital
🇯🇵Kagoshima-shi, Kagoshima, Japan
The Institute of Medical Science, The University of Tokyo
🇯🇵Minato-ku, Tokyo, Japan
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Nagasaki University Hospital
🇯🇵Nagasaki-shi, Nagasaki, Japan
University of the Ryukyus Hospital
🇯🇵Nakagami-gun, Okinawa, Japan
National Cancer Center Hospital
🇯🇵Chuo Ku, Toyko, Japan
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States