JOURNAL ONKOLOGIE – STUDIE

A Study Evaluating the Safety, Efficacy, and Pharmacokinetics of Mosunetuzumab and a Combined Regimen of Mosunetuzumab and Venetoclax in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia

Studien-Informationen Einschlusskriterien Studien-Rationale Studien-Arme Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT05091424

Studienbeginn:
März 2022

Letztes Update:
03.05.2024

Wirkstoff:
Mosunetuzumab, Tocilizumab, Venetoclax

Indikation (Clinical Trials):
Leukemia, Leukemia, Lymphoid, Leukemia, Lymphocytic, Chronic, B-Cell

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 1

Sponsor:
Hoffmann-La Roche

Collaborator:
-

Studienleiter

Clinical Trials
Study Director
Hoffmann-La Roche

Kontakt

Reference Study ID Number: BO43243 https://forpatients.roche.com/
Kontakt:
Phone: 888-662-6728
E-Mail: global-roche-genentech-trials@gene.com» Kontaktdaten anzeigen

Studienlocations
(3 von 18)

Universitätsklinikum Augsburg; II. Med. Klinik
86156 Augsburg
(Bayern)
GermanyRekrutierend» Google-Maps

Uniklinik Koln; Klinik I fur Innere Medizin
50937 Köln
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps

Universitätsklinikum Ulm; Medizinische Uni-Klinik III Abt. Innere Medizin III Hämatologie u. Onkolo.
89081 Ulm
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps

Mayo Clinic Rochester
55902 Rochester
United StatesRekrutierend» Google-Maps

Memorial Sloan-Kettering Cancer Center; Hematology/Oncology
10065 New York
United StatesRekrutierend» Google-Maps

Uni of Texas - Md Anderson Cancer Center; Dept of Leukemia
77030 Houston
United StatesRekrutierend» Google-Maps

Princess Alexandra Hospital Woolloongabba; Clinical Hematology and Medical Oncology
4102 Woolloongabba
AustraliaRekrutierend» Google-Maps

Monash Medical Centre; Haematology
3168 Melbourne
AustraliaRekrutierend» Google-Maps

Peter MacCallum Cancer Center
3051 North Melbourne
AustraliaRekrutierend» Google-Maps

CHU DE CLERMONT FERRAND; Service de Thérapie Cellulaire et d'Hématologie clinique adultes
63003 Clermont-Ferrand
FranceSchwebend» Google-Maps

IUCT Oncopole; Hematologie
31059 Toulouse
FranceRekrutierend» Google-Maps

A.O. Spedali Civili Di Brescia-P.O. Spedali Civili;U.O. Ematologia
25123 Brescia
ItalyRekrutierend» Google-Maps

Osp. San Raffaele; Dip. Di Oncoematologia
20132 Milano
ItalyRekrutierend» Google-Maps

ASST GRANDE OSPEDALE METROPOLITANO NIGUARDA; Struttura Complessa di Ematologia
20162 Milano
ItalyAbgeschlossen» Google-Maps

Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia; Oncologia Medica
06132 Sant'Andrea Delle Fratte (PG)
ItalyRekrutierend» Google-Maps

Hospital de la Santa Creu i Sant Pau; Servicio de Hematologia
08025 Barcelona
SpainRekrutierend» Google-Maps

Hospital Universitari Vall d'Hebron; Servicio de Hematologia
08035 Barcelona
SpainRekrutierend» Google-Maps

Churchill Hospital; Department of Oncology
OX3 7LE Oxford
United KingdomRekrutierend» Google-Maps

Alle anzeigen

Studien-Informationen

Brief Summary:

This study will assess the safety, tolerability, pharmaokinetics, and preliminary efficacy of

mosunetuzumab (Lunsumio) monotherapy in participants with relapsed or refractory (R/R)

chronic lymphocytic leukemia (CLL). This study will also allow participants who are currently

progressing on a Bruton tyrosine kinase inhibitor (BTKi) and requiring salvage therapy as

assessed by the treating physician to continue their BTKi throughout the screening period and

for the first two cycles of mosunetuzumab. An additional arm has been added to assess the

safety, tolerability, pharmacokinetics, and preliminary efficacy of mosunetuzumab in

combination with venetoclax, a B-cell lymphoma 2 (BCL2) inhibitor.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Have a diagnosis of CLL requiring treatment according to the International Workshop on

CLL (iwCLL) criteria (Hallek et al 2018)

- Eastern Cooperative Oncology Group (ECOG) performance score (PS) of ≤ 2

- Adequate bone marrow (BM) function independent of growth factor or transfusion

support, within 2 weeks of screening, at screening as defined by the protocol unless

cytopenia is clearly due to marrow involvement of CLL

- Adequate liver function unless directly attributable to the participant's CLL

- Life expectancy > 6 months

- For women of childbearing potential: agreement to remain abstinent (refrain from

heterosexual intercourse) or use contraceptive methods that result in a failure rate

of < 1% per year, and agreement to refrain from donating eggs during the treatment

period and for at least 3 months after the last dose of mosunetuzumab and 3 months

after the last dose of tocilizumab (if applicable)

- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use

a condom, and agreement to refrain from donating sperm as defined by the protocol

Inclusion Criteria Specific to Arm B:

- Participants must have been taking a BTKi for at least 12 months, have demonstrated

evidence of progressive disease while receiving the BTKi and require additional

salvage therapy as assessed by their treating physician. Participants should be able

to continue their previously prescribed BTKi at a stable dose throughout the study

screening period and for the first two cycles of mosunetuzumab administration

Exclusion Criteria:

- Pregnant or breastfeeding, or intending to become pregnant during the study or within

3 months after the final dose of mosunetuzumab and tocilizumab or within 30 days after

the final dose of venetoclax (if applicable)

- Participants who have received any of the following treatments prior to study entry:

treatment with mosunetuzumab or other CD20/CD3-directed bispecific antibodies;

allogenic stem cell transplant

- Participants who have received any of the following treatments, whether

investigational or approved, within the respective time periods prior to initiation of

study treatment: radiotherapy within 2 weeks prior to the first dose of study

treatment; autologous stem cell transplant within 100 days prior to first study

treatment; CAR T-cell therapy within 30 days before first study treatment; prior use

of any monoclonal antibodies, radioimmunoconjugates, or antibody-drug conjugates for

anti-CLL treatment within 4 weeks before first dose of study treatment; systemic

immunosuppressive medications (including but not limited to cyclophosphamide,

azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within

2 weeks prior to the first dose of study treatment; any other anti-cancer therapy,

whether investigational or approved, including but not limited to chemotherapy within

4 weeks prior to initiation of study treatment (except for participants enrolled in

Arm B, where overlapping therapy is permitted; other prior cancer immunotherapy not

explicitly defined by the protocol is to be discussed with the medical monitor to

determine eligibility

- Received a live, attenuated vaccine within 4 weeks before the first dose of study

treatment, or in whom it is anticipated that such a vaccine will be required during

the study period or within 5 months after the final dose of study treatment

- Transformation of CLL to aggressive non-Hodgkin's lymphoma (NHL)

- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal

antibody therapy (or recombinant antibody-related fusion proteins)

- Contraindication to tocilizumab

- History of prior malignancy except for conditions defined by the protocol

- Participants with infections requiring intravenous (IV) treatment with antibiotics or

hospitalization within the last 4 weeks prior to enrollment or known active bacterial,

viral (including SARS-CoV-2), fungal, mycobacterial, parasitic, or other infection

(excluding fungal infections of nail beds) at study enrollment

- Evidence of any significant concomitant disease that could affect compliance with the

protocol or interpretation of results

- Recent major surgery within 4 weeks prior to first study treatment administration,

with the exception of protocol-mandated procedures (e.g., tumor biopsies and bone

marrow biopsies)

- Positive SARS-CoV-2 test within 7 days prior to enrollment

Exclusion Criteria Specific to Arm C:

- Have received venetoclax therapy within 12 months prior to first study treatment

administration

- Participants with known infection with HIV or human T-cell leukemia virus 1 (HTLV1)

- HIV testing will be performed in countries where mandatory testing by health

authorities is required

- HTLV testing is required in participants from endemic countries

- Participants with uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia

- Participants who have received the following: strong and moderate CYP3A inhibitors

within 7 days prior to the initiation of study treatment; strong and moderate CYP3A

inducers within 7 days prior to the initiation of study treatment; steroid therapy for

anti-neoplastic intent with the exception of inhaled steroids for asthma, topical

steroids, or replacement/stress corticosteroids within 7 days prior to the first dose

of study drug administration

- Have consumed grapefruit, grapefruit products, Seville oranges (including marmalade

containing Seville oranges), or star fruit within 3 days prior to the first dose of

study drug and throughout venetoclax administration

- Inability to swallow a large number of tablets

- Malabsorption syndrome or other condition that precludes enteral route of

administration

- Known allergy to both xanthine oxidase inhibitors and rasburicase

Studien-Rationale

Primary outcome:

1. Rate of Dose-Limiting Toxicities (DLTs) (Time Frame - Up to approximately 12 months (Arms A and B) or 24 months (Arm C))

Secondary outcome:

1. Objective Response Rate (ORR) (Time Frame - Up to 8-12 weeks after the last dose of study drug)

2. Minimal Residual Disease (MRD) Response Rate (Time Frame - Up to 8-12 weeks after the last dose of study drug)

3. Progression-Free Survival (PFS) (Time Frame - From the first study treatment to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 12 months (Arms A and B) or 24 months (Arm C)))

4. Overall Survival (OS) (Time Frame - From the first dose of study drug to death from any cause (up to approximately 12 months (Arms A and B) or 24 months (Arm C)))

5. Event-Free Survival (EFS) (Time Frame - Between the date of the first study treatment to the date of disease progression/relapse, death, or start of new anti-leukemic therapy, whichever occurs first (up to approximately 12 months (Arms A and B) or 24 months (Arm C)))

6. Complete Response (CR) Rate (Time Frame - Up to 8-12 weeks after the last dose of study drug)

7. Duration of Response (DOR) (Time Frame - From the first occurrence of a documented objective response to disease progression by iwCLL 2018 criteria or death from any cause (up to approximately 12 months (Arms A and B) or 24 months (Arm C)))

8. Percentage of Participants with Adverse Events (AEs) (Time Frame - Up to approximately 12 months (Arms A and B) or 24 months (Arm C))

9. Maximum Serum Concentration (Cmax) of Mosunetuzumab SC (Time Frame - Up to approximately 12 months (Arms A and B) or 24 months (Arm C))

10. Minimum Serum Concentration (Cmin) of Mosunetuzumab SC (Time Frame - Up to approximately 12 months (Arms A and B) or 24 months (Arm C))

11. Time to Maximum Concentration (Tmax) of Mosunetuzumab SC (Time Frame - Up to approximately 12 months (Arms A and B) or 24 months (Arm C))

12. Incidence of Anti-Drug Antibodies (ADAs) (Time Frame - Baseline through end of study (up to approximately 12 months for Arms A and B, or 24 months for Arm C))

Studien-Arme

Experimental: Arm A
Participants with R/R CLL who have failed two prior lines of therapy and who have had prior exposure to BTKi and/or venetoclax will receive mosunetuzumab subcutaneous (SC) monotherapy
Experimental: Arm B
Participants with R/R CLL who have failed two prior lines of therapy, who are currently progressing on BTKi therapy, and who require salvage therapy as assessed by their treating physician will receive mosunetuzumab SC with BTKi overlap therapy for the first two cycles of mosunetuzumab SC
Experimental: Arm C
Participants with R/R CLL who have failed two prior lines of therapy and who have had prior exposure to BTKi and/or venetoclax will receive mosunetuzumab SC with venetoclax

Geprüfte Regime

Mosunetuzumab (Lunsumio):
Participants will receive subcutaneous (SC) mosunetuzumab
Tocilizumab:
Participants will receive intravenous (IV) tocilizumab as needed for cytokine release syndrome (CRS) events.
Venetoclax (Venclyxto / Venclexta / ):
Participants will receive daily oral venetoclax

Quelle: ClinicalTrials.gov

Sie können folgenden Inhalt einem Kollegen empfehlen:

"A Study Evaluating the Safety, Efficacy, and Pharmacokinetics of Mosunetuzumab and a Combined Regimen of Mosunetuzumab and Venetoclax in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia"

Bitte tragen Sie auch die Absenderdaten vollständig ein, damit Sie der Empfänger erkennen kann.

Die mit (*) gekennzeichneten Angaben müssen eingetragen werden!