DS-3201b in Participants With Lymphomas

Non-hodgkin Lymphoma Clinical Trial

Official title:

A Phase 1 Multiple Ascending Dose Study of DS-3201b in Subjects With Lymphomas

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02732275
• Other study ID #: DS3201-A-J101
• Secondary ID: 163173
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: March 31, 2016
• Est. completion date: December 31, 2024

Study information

• Verified date: April 2024
• Source: Daiichi Sankyo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 100
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Malignant
• Non-hodgkin Lymphoma

Intervention

Drug:
• DS-3201b

Locations

Country	Name	City	State
Japan	National Cancer Center Hospital	Chuo Ku	Toyko
Japan	Imamura General Hospital	Kagoshima-shi	Kagoshima
Japan	Kagoshima University Hospital	Kagoshima-shi	Kagoshima
Japan	National Cancer Center Hospital East	Kahiwa-shi	Chiba
Japan	Kumamoto University Hosipital	Kumamoto-shi	Kumamoto
Japan	The Institute of Medical Science, The University of Tokyo	Minato-ku	Tokyo
Japan	Iwate Medical University Hospital	Morioka-shi	Iwate
Japan	Nagasaki University Hospital	Nagasaki-shi	Nagasaki
Japan	Nagoya City University Hospital	Nagoya-shi	Aichi
Japan	University of the Ryukyus Hospital	Nakagami-gun	Okinawa
United States	Emory University	Atlanta	Georgia
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	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	Duke University Medical Center	Durham	North Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Yale University	New Haven	Connecticut
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Weill Cornell Medicine	New York	New York
United States	Thomas Jefferson University	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Daiichi Sankyo Co., Ltd.	Daiichi Sankyo

Countries where clinical trial is conducted

United States,  Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Escalation Period: Number of participants with dose-limiting toxicities (DLTs)	Number of DLT-evaluable participants with protocol-defined DLTs	within 28 days after the initial dose of the study drug
Primary	Dose Escalation Period: Maximum concentration (Cmax) of DS-3201	Categories: Cycle 1 Day 1, Cycle 1 Day 15	within the first 28-day cycle
Primary	Dose Escalation Period: Time of maximum concentration (Tmax) of DS-3201	Categories: Cycle 1 Day 1, Cycle 1 Day 15	within the first 28-day cycle
Primary	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
Primary	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
Primary	Dose Escalation Period: Trough (minimum) plasma concentration (Ctrough)		Day 15 of the first 28-day cycle
Primary	Dose Escalation Period: Average plasma concentration (Cavg)		Day 15 of the first 28-day cycle
Primary	DDI cohort only: Maximum concentration (Cmax) of DS-3201, midazolam, digoxin	Categories: Day -4, Cycle 1 Day 1, Cycle 1 Day 15	within the first 28-day cycle
Primary	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	within the first 28-day cycle
Primary	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	within the first 28-day cycle
Primary	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	within the first 28-day cycle
Primary	Number of participants with treatment-emergent adverse events (TEAEs)	TEAEs are systematically collected from lab values, physical exams, and other investigations	through the end of the study (within approximately 5 years)
Secondary	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	from the start of study treatment to the end of follow-up visit (within 5 years)
Secondary	Objective response rate (ORR)	ORR is defined as the percentage of participants who were assessed for best overall response, who achieved CR, UCR, or PR	within 5 years
Secondary	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, UCR, PR, or SD	within 5 years
Secondary	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.	within 5 years
Secondary	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.	witihn 5 years
Secondary	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)	through the end of the study (within approximately 5 years)
Secondary	Number of participants with ATL who achieved each level of therapeutic response per international consensus standards	Categories: CR, Uncertified complete remission (CRu), PR, SD, RD/PD, Unassessable (UA)	through the end of the study (within approximately 5 years)
Secondary	Number of participants with CTCL who achieved response per 2011 CTCL criteria	Categories: CR,PR,SD,PD,Relapse	through the end of the study (within approximately 5 years)