Etude : CAPITAL / D361FC00001



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Acronyme / Nom
Situation thérapeutique
Traitement
Cadre réglementaire
MÀJ
Présentation de l'étude
Acronyme / Nom : CAPITAL / D361FC00001

Situation thérapeutique : Induction

Traitement : Thérapie ciblée

Cadre réglementaire : RIPH1

Dernière MÀJ : 07/01/2022
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
Titre : A Modular Phase II, Open-Label, Multicentre Study to Assess the Efficacy and Safety of Capivasertib in Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (CAPITAL)

Spécialité : Tissus lymphoïde, hématopoïétique et apparentés
Localisation : C82 - Lymphome folliculaire

Spécialité : Tissus lymphoïde, hématopoïétique et apparentés
Localisation : C83 - Lymphome non folliculaire
Schéma
Phase
Stade
Ligne(s)
Informations complémentaires
Schéma : The study protocol follows a modular design. The study will investigate the safety and efficacy of capivasertib monotherapy in participants with R/R Follicular Lymphoma (FL), Marginal Zone Lymphoma (MZL), and Mantle Cell Lymphoma (MCL).

Single Group Assignment:
Experimental: Capivasertib monotherapy
Participants with R/R FL, R/R MZL, and R/R MCL will receive capivasertib orally until progression of disease (PD) or unacceptable toxicity.
Capivasertib will be given twice a day, intermittently.

Main Objective:
To estimate the effectiveness of the module-defined study treatment by assessment of Objective Response Rate (ORR) based on Lugano 2014 Classification response criteria in each cohort as determined by Blinded Independent Central Review (BICR)

Secondary Objectives:
1. To estimate the effectiveness of the module-defined study-treatment by assessment of Duration of Response (DoR)
2. To estimate the effectiveness of the module-defined study treatment by assessment of Progression-Free Survival (PFS)
3. To estimate the effectiveness of the module-defined study treatment by assessment of Overall Survival (OS)
4. To assess patient-reported disease-related symptoms, functioning and health-related quality of life of the module-defined study treatment
5. To assess patient-reported symptomatic AEs / tolerability of module-defined study treatment
6. To estimate the effectiveness of the module-defined study treatment by assessment of Time to First Subsequent therapy or death (TFST) in each cohort
7. To estimate the effectiveness of the module-defined study treatment by assessment of time to objective response (TTR) in each cohort
8. To assess safety and tolerability of the module-defined study treatment
9. To determine the PK of Capivasertib

Phase : II

Stade : NA

Rechute, Réfractaire
Critères d'inclusion
Critères de non-inclusion
Critères d'inclusion et de non-inclusion
Critères d'inclusion : - Patient must be >/= 18 years of age, at the time of signing the informed consent
- ECOG performance status = 2
- Life expectancy > 6 months
- Female patients must not be breast-feeding and must have a negative pregnancy test prior to start of dosing

--- Additional core inclusion criteria may apply, please refer to the protocol ---

Module 1 specific inclusion criteria:

Additional Inclusion Criteria for Cohort 1A (R/R FL):
1. Histologically confirmed diagnosis of FL Grade 1, 2, or 3a as assessed by investigator or local pathologist
2. Current need for systemic treatment based on the Investigator’s opinion
3. Relapsed, progressed or refractory (defined as failure to achieve at least a PR) after at least 2 prior systemic lines of therapy (including anti-CD20mAb and an alkylating agent)
4. Patients should have received up to a maximum of 5 lines of prior therapies.
5. Bi-dimensionally measurable disease on cross sectional imaging by CT or MRI with at least one nodal lesion > 1.5 cm in the long axis or at least one extranodal lesion > 1 cm in long axis.

Additional Inclusion Criteria for Cohort 1B (R/R MZL):
1. Histologically confirmed MZL including splenic, nodal, and extranodal subtypes as assessed by investigator or local pathologist.
2. Current need for systemic treatment based on the Investigator’s opinion.
3. Relapsed, progressed or refractory (defined as failure to achieve at least a PR) after at least 2 prior systemic lines of therapy (including at least one anti-CD20mAb directed regimen either as monotherapy or as chemoimmunotherapy; Helicobacter pylori eradication and radiation therapy alone will not be considered a systemic treatment regimen).
4. Patients should have received up to a maximum of 5 lines of prior therapies.
5. Bi-dimensionally measurable disease on cross sectional imaging by CT or MRI with at least one nodal lesion > 1.5 cm in the long axis or at least one extranodal lesion > 1 cm in long axis.

Additional Inclusion Criteria for Cohort 1C (R/R MCL):
1. Histologically confirmed MCL, with documentation of monoclonal B cells that have a chromosome translocation t(11;14)(q13;q32) and/or overexpress cyclin D1, as assessed by investigator or local pathologist.
2. Relapsed, progressed or refractory (defined as failure to achieve at least a PR) after at least 2 prior systemic lines of therapy.
3. Patients should have received up to a maximum of 4 lines of prior therapies.
Prior regimens must have included:
- BTK inhibitor and
- Anti-CD20 monoclonal antibody therapy
4. Bi-dimensionally measurable disease on cross sectional imaging by CT or MRI with at least one nodal lesion > 1.5 cm in the long axis or at least one extranodal lesion > 1 cm in long axis.

Critères de non-inclusion : - Prior malignancy (other than the disease under study), except for adequately treated basal cell or squamous cell skin cancer, in situ cancer, or other cancer from which the patient has been disease free for >/= 2 years
- With the exception of alopecia, any unresolved non-haematological toxicities from prior therapy >/= CTCAE Grade 2 at the time of starting study treatment
- Known medically apparent CNS lymphoma or leptomeningeal disease
- Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values at screening:
a) Absolute neutrophil count < 1.0 × 10^9/L; < 0.75 × 10^9/L in participants with known bone marrow involvement of malignant disease
b) Platelets < 75 × 10^9/L; < 50 × 10^9/L in participants with known bone marrow involvement of malignant disease
c) Creatinine clearance < 50 mL/min per the Cockcroft and Gault formula

- Clinically significant abnormalities of glucose metabolism as participants with diabetes mellitus type I or diabetes mellitus type II requiring insulin treatment and Glycosylated haemoglobin >/= 8.0% (63.9 mmol/mol)
- Prior treatment with any of the following:
a) Any investigational agents or study drugs from a previous clinical study within 5 half lives or 2 weeks from the first dose of capivasertib in this study
b) Potent inhibitors or inducers of CYP3A4 and/or UGT2B7 within 2 weeks prior to the first dose of study treatment (3 weeks for St John’s wort), or sensitive substrates of CYP3A4, CYP2C9 and/or CYP2D6 with a narrow therapeutic window within 1 week prior to the first dose of study treatment.
c) Prior allogenic HSCT within 6 months from the first dose of capivasertib (patients > 6 months after allogenic HSCT are eligible in the absence of active graft-versus-host disease and concomitant immune suppressive therapy). Prior cellular therapies (eg, CAR-T therapy) and/or autologous HSCT within 3 months from the first dose of capivasertib.
d) Receipt of live, attenuated vaccine within 28 days before the first dose of study treatment(s).
e) Patients who, due to other medical conditions /prior history /concomitant medications are, in the investigator's opinion, at a risk of a VTE and are not willing to accept the VTE prophylaxis, will be excluded. The initiation of an adequate VTE prophylaxis will be based on treating physician risk/benefit assessment and in agreement with the local management guidelines.

--- Additional exclusion core criteria may apply, please refer to the protocol ---
NCT
Promoteur
Coordonnateur
Informations relatives au promoteur
NCT :
NCT05008055
Promoteur :
AstraZeneca
Type de sponsor : Industriel
00000 HORS FRANCE

Coordonnateur :
Centre investigateur
Investigateur
TEC / ARC / IDE
État
MÀJ
Informations relatives aux investigateurs
Centre investigateur :
Centre Hospitalier Universitaire de Lille - 2 Avenue Oscar Lambret - 59000 LILLE

Investigateur :
Professeur Franck MORSCHHAUSER

TEC / ARC / IDE :
Secrétariat de recherche
fanny.miquel@
chru-lille.fr
03.20.44.57.13

Statut de l'essai : À VENIR

MAJ : 07/01/2022