Etude : VALENTINE-PTCL01 / DS3201-A-U202

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Acronyme / Nom
Situation thérapeutique
Cadre réglementaire
Présentation de l'étude
Acronyme / Nom : VALENTINE-PTCL01 / DS3201-A-U202

Situation thérapeutique : Induction

Traitement : Thérapie ciblée

Cadre réglementaire : RIPH1

Dernière MÀJ : 29/11/2021
CIM10 - Localisation(s)
Informations principales
Titre : Single-arm, Phase 2 Study of Valemetostat Tosylate Monotherapy in Subjects With Relapsed/Refractory Peripheral T-Cell Lymphoma

Spécialité : Tissus lymphoïde, hématopoïétique et apparentés
Localisation : C84 - Lymphomes à cellules T/NK matures

Spécialité : Tissus lymphoïde, hématopoïétique et apparentés
Localisation : C86 - Autres types précisés de lymphomes à cellules T/NK

Spécialité : Tissus lymphoïde, hématopoïétique et apparentés
Localisation : C91 - Leucémie lymphoïde
Informations complémentaires
Schéma : 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, including relapsed/refractory adult T-cell leukemia/lymphoma participants.

- Experimental: Cohort 1: Relapsed/Refractory Peripheral T-Cell Lymphoma
Participants who will receive 200 mg/day valemetostat tosylate and had an eligible peripheral T-cell lymphoma subtype that was confirmed by independent hematopathology central review.

- Experimental: Cohort 2: Relapsed/Refractory Adult T-cell Leukemia/Lymphoma
Participants who will receive 200 mg/day valemetostat tosylate and had an eligible adult T-cell leukemia/lymphoma subtype that was confirmed by the local pathologist/investigators and by documented positive anti-human T-cell leukemia virus type 1 (HTLV-1) antibody.

Drug: Valemetostat Tosylate
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

To estimate the objective response rate (ORR) with valemetostat tosylate monotherapy treatment in R/R PTCL, including R/R ATL. Subjects with R/R ATL are to be enrolled in a separate cohort and will be analyzed independently.

- To evaluate the duration of response (DoR);
- To assess the CR rate;
- To evaluate the duration of CR (DoCR);
- To assess the PR rate;
- To assess the safety and tolerability of valemetostat tosylate monotherapy.

Phase : II

Stade : NA

Rechute, Réfractaire
Informations libres de droit
Critères d'inclusion
Critères de non-inclusion
Informations libres de droit
Critères d'inclusion et de non-inclusion
Critères d'inclusion : 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. 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). R/R ATL should be pathologically or hematocytologically confirmed by the local pathologist/investigators; local histological/ hematocytologically diagnosis will be used for eligibility determination. The positivity of anti-HTLV-1 antibody will be locally determined for eligibility.
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 refractory, relapsed, or progressive disease after at least 1 prior line of systemic therapy.
Refractory is defined as
• 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 first-line therapy
• Failure to reach at least PR or stable disease).following second-line therapy or beyond
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; the reason for HCT ineligibility 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 ---

Critères de non-inclusion : 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 systemic immunosuppressive prophylaxis or treatment
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 interval (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 replacement) is permissible.

--- Please refer to the protocol for the full list of exclusion criteria ---
Informations relatives au promoteur
Promoteur :
Type de sponsor : Industriel

Coordonnateur :
Centre investigateur
Informations relatives aux investigateurs
Centre investigateur :
Centre Hospitalier Universitaire de Lille - 2 Avenue Oscar Lambret - 59000 LILLE

Investigateur :
Professeur Franck MORSCHHAUSER

Secrétariat de recherche

Statut de l'essai : À VENIR

MAJ : 22/11/2021