Clinical trial NCT02732275: DS-3201b in Participants With Lymphomas
Official title: A Phase 1 Multiple Ascending Dose Study of DS-3201b in Subjects With Lymphomas
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Lymphoma, Malignant
Non-hodgkin Lymphoma
Keywords: Adult T-cell leukemia-lymphoma (ATL)
Peripheral T-cell lymphoma (PTCL)
Cutaneous T-cell lymphoma (CTCL)
B-cell lymphoma
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
Collaborators: name: Daiichi Sankyo
First posted: 2016-04-08
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: Inclusion Criteria:

* 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:

  1. willing to provide archived or fresh tumor tissue samples that are sufficient for comprehensive genomic and/or proteomic analyses at baseline
  2. \[US only\] 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
  3. 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Dose Escalation Period: Number of participants with dose-limiting toxicities (DLTs)
timeFrame: within 28 days after the initial dose of the study drug
measure: Dose Escalation Period: Maximum concentration (Cmax) of DS-3201
timeFrame: within the first 28-day cycle
measure: Dose Escalation Period: Time of maximum concentration (Tmax) of DS-3201
timeFrame: within the first 28-day cycle
measure: Dose Escalation Period: Area under the plasma concentration time curve up to the last quantifiable time (AUClast) for DS-3201
timeFrame: Day 1 of the first 28-day cycle
measure: Dose Escalation Period: Area under the plasma concentration time curve during the dosing interval (AUCtau) for DS-3201
timeFrame: Day 1 of the first 28-day cycle
measure: Dose Escalation Period: Trough (minimum) plasma concentration (Ctrough)
timeFrame: Day 15 of the first 28-day cycle
measure: Dose Escalation Period: Average plasma concentration (Cavg)
timeFrame: Day 15 of the first 28-day cycle
measure: DDI cohort only: Maximum concentration (Cmax) of DS-3201, midazolam, digoxin
timeFrame: within the first 28-day cycle
measure: DDI cohort only: Time of maximum concentration (Tmax) of DS-3201, midazolam, digoxin
timeFrame: within the first 28-day cycle
measure: DDI cohort only: Area under the plasma concentration time curve up to the last quantifiable time (AUClast) for DS-3201,midazolam,digoxin
timeFrame: within the first 28-day cycle
measure: DDI cohort only: Area under the plasma concentration time curve during the dosing interval (AUCtau) for DS-3201, midazolam, digoxin
timeFrame: within the first 28-day cycle
measure: Number of participants with treatment-emergent adverse events (TEAEs)
timeFrame: through the end of the study (within approximately 5 years)
Secondary outcomes:
measure: Best overall response, based on international consensus criteria
timeFrame: from the start of study treatment to the end of follow-up visit (within 5 years)
measure: Objective response rate (ORR)
timeFrame: within 5 years
measure: Disease control rate (DCR)
timeFrame: within 5 years
measure: Duration of response (DOR)
timeFrame: within 5 years
measure: Progression-free survival (PFS)
timeFrame: witihn 5 years
measure: Number of participants with malignant lymphoma who achieved each level of therapeutic response per international consensus standards
timeFrame: through the end of the study (within approximately 5 years)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical center
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center and James Cancer Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Nagoya-shi
country: Japan
facility: Nagoya City University Hospital
state: Aichi
city: Kahiwa-shi
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Morioka-shi
country: Japan
facility: Iwate Medical University Hospital
state: Iwate
city: Kagoshima-shi
country: Japan
facility: Imamura General Hospital
state: Kagoshima
city: Kagoshima-shi
country: Japan
facility: Kagoshima University Hospital
state: Kagoshima
city: Kumamoto-shi
country: Japan
facility: Kumamoto University Hosipital
state: Kumamoto
city: Nagasaki-shi
country: Japan
facility: Nagasaki University Hospital
state: Nagasaki
city: Nakagami-gun
country: Japan
facility: University of the Ryukyus Hospital
state: Okinawa
city: Minato-ku
country: Japan
facility: The Institute of Medical Science, The University of Tokyo
state: Tokyo
city: Chuo Ku
country: Japan
facility: National Cancer Center Hospital
state: Toyko
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader, MD
role: STUDY_DIRECTOR
References: