Relapsed/Refractory Peripheral T-Cell Lymphoma, Adult T Cell Leukemia/Lymphoma
Conditions
Keywords
Relapsed/Refractory Peripheral T-Cell Lymphoma, Adult T-Cell Leukemia/Lymphoma, Valemetostat Tosylate, DS-3201b
Brief summary
This study will characterize the safety and clinical benefit of valemetostat tosylate in participants with relapsed/refractory peripheral T-cell lymphoma, including relapsed/refractory adult T-cell leukemia/lymphoma.
Detailed description
This study was designed to evaluate the efficacy and safety of valemetostat tosylate monotherapy. The primary objective will evaluate objective response rate of valemetostat tosylate monotherapy as measured by blinded independent central review (BICR) in relapsed/refractory peripheral T-cell lymphoma.
Interventions
Oral administration of valemetostat tosylate at a dose of 200 mg once daily starting at Cycle 1, Day 1 (continuous for 28-day cycles), until disease progression or unacceptable toxicity
Sponsors
Daiichi Sankyo
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Written informed consent * Participants ≥18 years of age or the minimum legal adult age (whichever is greater) at the time the informed consent form is signed. * Eastern Cooperative Oncology Group performance status of 0, 1, or 2 * Cohort 1 relapsed/refractory peripheral T-cell lymphoma (PTCL): * Diagnosis should be confirmed by the local pathologist; local histological diagnosis will be used for eligibility determination. Participants with the following subtypes of PTCL are eligible according to 2016 WHO classification prior to the initiation of study drug. Any T-cell lymphoid malignancies not listed are excluded. Eligible subtypes include: * Enteropathy-associated T-cell lymphoma * Monomorphic epitheliotropic intestinal T-cell lymphoma * Hepatosplenic T-cell lymphoma * Primary cutaneous γδ T-cell lymphoma * Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma * PTCL, not otherwise specified * Angioimmunoblastic T-cell lymphoma * Follicular T-cell lymphoma * Nodal PTCL with T-follicular helper (TFH) phenotype * Anaplastic large cell lymphoma, ALK positive * Anaplastic large cell lymphoma, ALK negative * Cohort 2 relapsed/refractory adult T-cell leukemia/lymphoma (ATL) acute, lymphoma, or unfavorable chronic type. Relapsed/refractory ATL should be confirmed by the local pathologist; local diagnosis will be used for eligibility determination. The positivity of anti-human T-cell leukemia virus type 1 (HTLV-1) antibody will be locally determined for eligibility. * Must have at least one lesion which is measurable in 2 perpendicular dimensions on computed tomography (or magnetic resonance imaging) based on local radiological read * Documented refractory, relapsed, or progressive disease after at least 1 prior line of systemic therapy. * Refractory is defined as: * Failure to achieve CR (or CRu for ATL) after first-line therapy * Failure to reach at least PR after second-line therapy or beyond * Must have at least 1 prior line of systemic therapy for PTCL or ATL. * Participants must be considered hematopoietic cell transplantation (HCT) ineligible during screening due to disease status (active disease), comorbidities, or other factors; the reason for HCT ineligibility must be clearly documented. * In the PTCL cohort, participants with anaplastic large cell lymphoma (ALCL) must have prior brentuximab vedotin treatment.
Exclusion criteria
Participants meeting any
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Objective Response As Assessed by Blinded Independent Central Review After Administration of Valemetostat Tosylate Monotherapy (Cohort 1) | From baseline until disease progression or death (whichever occurs first), up to approximately 23 months | For the relapsed/refractory peripheral T-cell lymphoma (PTCL) cohort, objective response rate (ORR) is defined as the proportion of participants with a best overall response (BOR) of complete response (CR) or partial response (PR), assessed by blinded independent central review (BICR), among participants with centrally confirmed PTCL eligible histology. |
| Number of Participants With Treatment-emergent Adverse Events After Administration of Valemetostat Tosylate Monotherapy (Cohort 2) | From the time the informed consent form is signed up to 30 days after last dose, up to 23 months | Treatment-emergent adverse events (TEAEs) were defined as new AEs or pre-existing conditions that worsen in National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) grade after the first dose of study drug and up to 30 days after the last dose of study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Complete Response After Administration of Valemetostat Tosylate Monotherapy (Cohort 1) | From baseline to date of first documented objective response of CR, up to approximately 56 months | Complete response rate is the percentage of participants achieving CR as the BOR based on BICR assessments. |
| Duration of Complete Response After Administration of Valemetostat Tosylate Monotherapy (Cohort 1) | Time from the date of first documented CR until documented disease progression (progressive or relapsed disease) based on BICR assessments or death from any cause (whichever occurs first), up to approximately 56 months | Duration of complete response is defined as the time from the date of the first documentation of CR to the date of the first documentation of disease progression (progressive or relapsed disease) based on BICR assessments or to death due to any cause, whichever occurs first. |
| Plasma Concentrations of DS-3201a and CALZ-1809a After Administration of Valemetostat Tosylate Monotherapy | Cycle 1 Day 1, 8, 15 Predose; Cycle 1 Day 1 (1, 2, 4, 5 hours Postdose); Cycle 2 Day 1 Predose; Cycle 3 Day 1 to Cycle 5 Day 1 Predose (each cycle is 28 days) | Total and unbound DS-3201a (free form of valemetostat tosylate) and total CALZ-1809a (major metabolite) concentration in plasma will be assessed. |
| Number of Participants With Treatment-emergent Adverse Events After Administration of Valemetostat Tosylate Monotherapy (Cohort 1) | From the time the informed consent form is signed up to 30 days after last dose | — |
| Percentage of Participants With Partial Response After Administration of Valemetostat Tosylate Monotherapy (Cohort 1) | From baseline to date of first documented objective response of PR, up to approximately 56 months | Partial response rate is the percentage of participants achieving PR as the BOR based on BICR assessment. |
| Duration of Response After Administration of Valemetostat Tosylate Monotherapy (Cohort 1) | Time from the date of first documented response (CR or PR) until documented disease progression (progressive or relapsed disease) based on BICR assessments or death from any cause (whichever occurs first), up to approximately 56 months | Duration of response (DoR) is defined as the time from the date of the first documentation of objective response (CR or PR) to the date of the first documentation of disease progression (progressive or relapsed disease) based on BICR assessments or to death due to any cause, whichever occurs first. |
Countries
Australia, Canada, France, Germany, Italy, Japan, Netherlands, South Korea, Spain, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
A total of 155 participants who met all inclusion criteria and no exclusion criteria were enrolled to receive valemetostat tosylate treatment in 70 study sites in North America, Europe, Asia, and Oceania.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Relapsed/Refractory Peripheral T-Cell Lymphoma (PTCL) Participants were administered valemetostat tosylate at a dose of 200 mg/day and had an eligible peripheral T-cell lymphoma . | 133 |
| Cohort 2: Relapsed/Refractory Adult T-cell Leukemia/Lymphoma Participants were administered valemetostat tosylate at a dose of 200 mg/day and had an eligible adult T-cell leukemia/lymphoma. | 22 |
| Total | 155 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 13 | 2 |
| Overall Study | Clinical Progression | 19 | 8 |
| Overall Study | Death | 3 | 1 |
| Overall Study | Hematopoietic Cell Transplantation | 12 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Other | 5 | 1 |
| Overall Study | Progressive or Relapsed Disease | 46 | 7 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Cohort 1: Relapsed/Refractory Peripheral T-Cell Lymphoma (PTCL) | Cohort 2: Relapsed/Refractory Adult T-cell Leukemia/Lymphoma | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 80 Participants | 12 Participants | 92 Participants |
| Age, Categorical Between 18 and 65 years | 53 Participants | 10 Participants | 63 Participants |
| Age, Continuous | 65.6 years STANDARD_DEVIATION 12.51 | 62.6 years STANDARD_DEVIATION 13.11 | 65.2 years STANDARD_DEVIATION 12.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 34 Participants | 8 Participants | 42 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 10 Participants | 16 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 12 Participants | 3 Participants | 15 Participants |
| Race (NIH/OMB) White | 80 Participants | 1 Participants | 81 Participants |
| Sex: Female, Male Female | 42 Participants | 7 Participants | 49 Participants |
| Sex: Female, Male Male | 91 Participants | 15 Participants | 106 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 52 / 133 | 16 / 22 |
| other Total, other adverse events | 120 / 133 | 22 / 22 |
| serious Total, serious adverse events | 53 / 133 | 15 / 22 |
Outcome results
Primary
Number of Participants With Treatment-emergent Adverse Events After Administration of Valemetostat Tosylate Monotherapy (Cohort 2)
Treatment-emergent adverse events (TEAEs) were defined as new AEs or pre-existing conditions that worsen in National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) grade after the first dose of study drug and up to 30 days after the last dose of study drug.
Time frame: From the time the informed consent form is signed up to 30 days after last dose, up to 23 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: Relapsed/Refractory Peripheral T-Cell Lymphoma (PTCL) | Number of Participants With Treatment-emergent Adverse Events After Administration of Valemetostat Tosylate Monotherapy (Cohort 2) | 22 Participants |
Primary
Percentage of Participants With Objective Response As Assessed by Blinded Independent Central Review After Administration of Valemetostat Tosylate Monotherapy (Cohort 1)
For the relapsed/refractory peripheral T-cell lymphoma (PTCL) cohort, objective response rate (ORR) is defined as the proportion of participants with a best overall response (BOR) of complete response (CR) or partial response (PR), assessed by blinded independent central review (BICR), among participants with centrally confirmed PTCL eligible histology.
Time frame: From baseline until disease progression or death (whichever occurs first), up to approximately 23 months
Population: Efficacy Analysis Set for Cohort 1 is defined as all subjects who received at least 1 dose of valemetostat tosylate and had an eligible PTCL subtype that was confirmed by central hematopathology review.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Relapsed/Refractory Peripheral T-Cell Lymphoma (PTCL) | Percentage of Participants With Objective Response As Assessed by Blinded Independent Central Review After Administration of Valemetostat Tosylate Monotherapy (Cohort 1) | 43.7 percentage of participants |
Secondary
Duration of Complete Response After Administration of Valemetostat Tosylate Monotherapy (Cohort 1)
Duration of complete response is defined as the time from the date of the first documentation of CR to the date of the first documentation of disease progression (progressive or relapsed disease) based on BICR assessments or to death due to any cause, whichever occurs first.
Time frame: Time from the date of first documented CR until documented disease progression (progressive or relapsed disease) based on BICR assessments or death from any cause (whichever occurs first), up to approximately 56 months
Secondary
Duration of Response After Administration of Valemetostat Tosylate Monotherapy (Cohort 1)
Duration of response (DoR) is defined as the time from the date of the first documentation of objective response (CR or PR) to the date of the first documentation of disease progression (progressive or relapsed disease) based on BICR assessments or to death due to any cause, whichever occurs first.
Time frame: Time from the date of first documented response (CR or PR) until documented disease progression (progressive or relapsed disease) based on BICR assessments or death from any cause (whichever occurs first), up to approximately 56 months
Secondary
Number of Participants With Treatment-emergent Adverse Events After Administration of Valemetostat Tosylate Monotherapy (Cohort 1)
Time frame: From the time the informed consent form is signed up to 30 days after last dose
Secondary
Percentage of Participants With Complete Response After Administration of Valemetostat Tosylate Monotherapy (Cohort 1)
Complete response rate is the percentage of participants achieving CR as the BOR based on BICR assessments.
Time frame: From baseline to date of first documented objective response of CR, up to approximately 56 months
Secondary
Percentage of Participants With Partial Response After Administration of Valemetostat Tosylate Monotherapy (Cohort 1)
Partial response rate is the percentage of participants achieving PR as the BOR based on BICR assessment.
Time frame: From baseline to date of first documented objective response of PR, up to approximately 56 months
Secondary
Plasma Concentrations of DS-3201a and CALZ-1809a After Administration of Valemetostat Tosylate Monotherapy
Total and unbound DS-3201a (free form of valemetostat tosylate) and total CALZ-1809a (major metabolite) concentration in plasma will be assessed.
Time frame: Cycle 1 Day 1, 8, 15 Predose; Cycle 1 Day 1 (1, 2, 4, 5 hours Postdose); Cycle 2 Day 1 Predose; Cycle 3 Day 1 to Cycle 5 Day 1 Predose (each cycle is 28 days)