Single-Arm, Phase 2 Study of Valemetostat Tosylate Monotherapy in Subjects with Relapsed/Refractory Peripheral T-Cell Lymphoma
- Conditions
- Non-Hodgkin's lymphomaPTCL10025321
- Registration Number
- NL-OMON51259
- Lead Sponsor
- Daiichi Sankyo Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 5
1. Sign and date the ICF, prior to the start of any study-specific
qualification procedures.
2. Subjects >=18 years of age or the minimum legal adult age (whichever is
greater) at the time the ICF is signed.
3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1,
or 2
4. Cohort 1 (R/R PTCL): Should be pathologically confirmed by the local
pathologist/investigators; local histological diagnosis will be used for
eligibility determination, but histology will be centrally reviewed following
study entry. Subjects with the following subtypes of PTCL are eligible,
according to 2016 World Health Organization classification prior to the
initiation of study drug. Any T-cell lymphoid malignancies not listed below are
excluded. Below is the complete list of eligible subtypes:
- 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 TFH phenotype
- Anaplastic large cell lymphoma, ALK positive
- Anaplastic large cell lymphoma, ALK negative
5. Cohort 2 (R/R ATL): (acute, lymphoma, or unfavorable chronic type) with
positive anti-human T-cell leukemia
virus type 1 (anti-HTLV-1) antibody. R/R ATL should be pathologically or
hematocytologically confirmed by the local pathologist/investigators. The
positivity of anti-HTLV-1 antibody will be locally confirmed.
6. Must have at least 1 of the following lesions which are measurable in 2
perpendicular dimensions on CT (or MRI) based on local radiological read:
- Longest diameter (LDi) >=2.0 cm for a nodal lesion
- LDi >1.0 cm for an extranodal lesion
For Cohort 2 (ATL), subjects who had disease only in peripheral blood or/and
skin lesions are eligible, as defined below.
o An abnormal lymphocyte count (actual number) is >=1.0 × 10^9 /L and the
abnormal lymphocyte-to-leucocyte ratio is >=5%.
o Skin lesion(s) measured by modified severity weighted assessment tool (mSWAT)
score.
7. Documented failure to achieve CR (or uncertified CR [CRu] for ATL) from
prior systemic lymphoma therapy, or relapsed disease (after CR or CRu for ATL),
or progressive disease (after PR or stable disease).
8. Must have at least 1 prior line of systemic therapy for PTCL or ATL.
- Subjects must also be considered as HCT-ineligible during Screening due to
disease status (active disease), comorbidities, or other factors; in case of
other factors, the eligibility should be discussed with the study medical
monitor, and the reason must be clearly documented.
- In Cohort 1, subjects with ALCL must have prior brentuximab vedotin treatment.
Please refer to the protocol for the full list of inclusion criteria.
1. Diagnosis of mycosis fungoides, Sézary syndrome, and primary cutaneous ALCL
and systemic dissemination of primary cutaneous ALCL
2. Diagnosis of precursor T-cell lymphoblastic leukemia and lymphoma (T-cell
acute lymphoblastic leukemia and T-cell lymphoblastic leukemia), T-cell
prolymphocytic leukemia, or T-cell large granular lymphocytic leukemia
3. Prior malignancy active within the previous 2 years except for locally
curable cancer that is currently considered as cured, such as cutaneous basal
or squamous cell carcinoma, superficial bladder cancer, or cervical carcinoma
in situ, or an incidental histological finding of prostate cancer
4. Presence of active central nervous system (CNS) involvement of lymphoma
5. History of autologous HCT within 60 days prior to first dose of study drug
6. History of allogeneic HCT within 90 days prior to the first dose of study
drug
7. Clinically significant graft-versus-host disease (GVHD) or GVHD requiring
initiation of systemic treatment or systemic treatment escalation
8. Inadequate washout period from prior lymphoma-directed therapy before
enrollment, defined as follows:
- Prior systemic therapy (eg, chemotherapy, immunomodulatory therapy, or
monoclonal antibody therapy) within 3 weeks prior to the first dose of study
drug
- Had curative radiation therapy or major surgery within 4 weeks or palliative
radiation therapy within 2 weeks prior to the first dose of study drug
9. Uncontrolled or significant cardiovascular disease, including the following:
- Evidence of prolongation of QT/QTc (eg, repeated episodes of QT corrected for
heart rate using Fridericia*s method [QTcF] >450 ms) (average of triplicate
determinations)
- Diagnosed or suspected long QT syndrome, or known family history of long QT
syndrome
- History of clinically relevant ventricular arrhythmias, such as ventricular
tachycardia, ventricular fibrillation, or Torsade de Pointes
- Uncontrolled arrhythmia (subjects with asymptomatic, controllable atrial
fibrillation may be enrolled), or asymptomatic persistent ventricular
tachycardia
- Subject has clinically relevant bradycardia of <50 bpm unless the subject
has a pacemaker
- History of second- or third-degree heart block. Candidates with a history of
heart block may be eligible if they currently have pacemakers, and have no
history of fainting or clinically relevant arrhythmia with pacemakers, within 6
months prior to Screening
- Myocardial infarction within 6 months prior to Screening
- Angioplasty or stent graft implantation within 6 months prior to Screening
- Uncontrolled angina pectoris within 6 months prior to Screening
- New York Heart Association (NYHA) Class 3 or 4 congestive heart failure
- Coronary/peripheral artery bypass graft within 6 months prior to Screening
- Uncontrolled hypertension (resting systolic blood pressure >180 mmHg or
diastolic blood pressure >110 mmHg)
- Complete left or right bundle branch block
10. History of treatment with other EZH inhibitors
11. Current use of moderate or strong cytochrome P450 (CYP)3A inducers (Table
10.4)
12. Systemic treatment with corticosteroids (>10 mg daily prednisone
equivalents). Note: Short-course systemic corticosteroids (eg,
prevention/treatment for transfusion reaction) or use for a non-cancer
indication (eg, adrenal rep
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Study Objective:<br /><br>• To estimate the objective response rate (ORR) with valemetostat tosylate<br /><br>monotherapy treatment in R/R PTCL, including R/R ATL.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary Study Objectives:<br /><br>• To evaluate the duration of response (DoR)<br /><br>• To assess the CR rate<br /><br>• To evaluate the duration of CR (DoCR)<br /><br>• To assess the PR rate<br /><br>• To assess the safety and tolerability of valemetostat tosylate monotherapy</p><br>