JOURNAL ONKOLOGIE – STUDIE

PHE885 CAR-T Therapy in Adult Participants With Relapsed and Refractory Multiple Myeloma

Studien-Informationen Einschlusskriterien Studien-Rationale Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT05172596

Studienbeginn:
März 2022

Letztes Update:
03.05.2024

Wirkstoff:
PHE885

Indikation (Clinical Trials):
Multiple Myeloma, Neoplasms, Plasma Cell

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
Novartis Pharmaceuticals

Collaborator:
-

Studienleiter

Novartis Pharmaceuticals
Study Director
Novartis Pharmaceuticals

Kontakt

Novartis Pharmaceuticals
Kontakt:
Phone: 1-888-669-6682
E-Mail: novartis.email@novartis.com» Kontaktdaten anzeigen

Novartis Pharmaceuticals
Kontakt:
Phone: +41613241111
» Kontaktdaten anzeigen

Studienlocations
(3 von 38)

Novartis Investigative Site
20246 Hamburg
(Hamburg)
GermanyAktiv, nicht rekrutierend» Google-Maps

Novartis Investigative Site
69120 Heidelberg
(Baden-Württemberg)
GermanyAktiv, nicht rekrutierend» Google-Maps

Novartis Investigative Site
50937 Koeln
(Nordrhein-Westfalen)
GermanyAktiv, nicht rekrutierend» Google-Maps

Novartis Investigative Site
97080 Wuerzburg
(Bayern)
GermanyAktiv, nicht rekrutierend» Google-Maps

Stanford University .
94304 Palo Alto
United StatesAktiv, nicht rekrutierend» Google-Maps

Emory University School of Medicine/Winship Cancer Institute
30322 Atlanta
United StatesAktiv, nicht rekrutierend» Google-Maps

Dana Farber Cancer Institute Main Site
02215 Boston
United StatesAktiv, nicht rekrutierend» Google-Maps

Oregon Health Sciences University .
97239 Portland
United StatesAktiv, nicht rekrutierend» Google-Maps

Thomas Jefferson University .
19107 Philadelphia
United StatesAktiv, nicht rekrutierend» Google-Maps

Fred Hutch Cancer Research
98109 Seattle
United StatesAktiv, nicht rekrutierend» Google-Maps

Novartis Investigative Site
3004 VIC
AustraliaAktiv, nicht rekrutierend» Google-Maps

Novartis Investigative Site
2050 Camperdown
AustraliaAktiv, nicht rekrutierend» Google-Maps

Novartis Investigative Site
41253-190 Salvador
BrazilAktiv, nicht rekrutierend» Google-Maps

Novartis Investigative Site
01323-900 Sao Paulo
BrazilRekrutierend» Google-Maps

Novartis Investigative Site
01509-900 São Paulo
BrazilAktiv, nicht rekrutierend» Google-Maps

Novartis Investigative Site
T2N 4N2 Calgary
CanadaAktiv, nicht rekrutierend» Google-Maps

Novartis Investigative Site
59037 Lille
FranceAktiv, nicht rekrutierend» Google-Maps

Novartis Investigative Site
44093 Nantes Cedex 1
FranceAktiv, nicht rekrutierend» Google-Maps

Novartis Investigative Site
75475 Paris 10
FranceAktiv, nicht rekrutierend» Google-Maps

Novartis Investigative Site
86021 Poitiers
FranceAktiv, nicht rekrutierend» Google-Maps

Novartis Investigative Site
570 10 Thessaloniki
GreeceAktiv, nicht rekrutierend» Google-Maps

Novartis Investigative Site
106 76 Athens
GreeceAktiv, nicht rekrutierend» Google-Maps

Novartis Investigative Site
52621 Ramat Gan
IsraelAktiv, nicht rekrutierend» Google-Maps

Novartis Investigative Site
6423906 Tel Aviv
IsraelAktiv, nicht rekrutierend» Google-Maps

Novartis Investigative Site
40138 Bologna
ItalyAktiv, nicht rekrutierend» Google-Maps

Novartis Investigative Site
20133 Milano
ItalyAktiv, nicht rekrutierend» Google-Maps

Novartis Investigative Site
467-8602 Nagoya-city
JapanAktiv, nicht rekrutierend» Google-Maps

Novartis Investigative Site
060 8648 Sapporo city
JapanAktiv, nicht rekrutierend» Google-Maps

Novartis Investigative Site
602-8566 Kyoto-city
JapanAktiv, nicht rekrutierend» Google-Maps

Novartis Investigative Site
980 8574 Sendai city
JapanAktiv, nicht rekrutierend» Google-Maps

Novartis Investigative Site
11211 Riyadh
Saudi ArabiaAktiv, nicht rekrutierend» Google-Maps

Novartis Investigative Site
119228 Singapore
SingaporeAktiv, nicht rekrutierend» Google-Maps

Novartis Investigative Site
169608 Singapore
SingaporeAktiv, nicht rekrutierend» Google-Maps

Novartis Investigative Site
37007 Salamanca
SpainAktiv, nicht rekrutierend» Google-Maps

Novartis Investigative Site
31008 Pamplona
SpainAktiv, nicht rekrutierend» Google-Maps

Novartis Investigative Site
B15 2TH Birmingham
United KingdomAktiv, nicht rekrutierend» Google-Maps

Novartis Investigative Site
G51 4TF Glasgow
United KingdomAktiv, nicht rekrutierend» Google-Maps

Novartis Investigative Site
M20 4BX Manchester
United KingdomAktiv, nicht rekrutierend» Google-Maps

Alle anzeigen

Studien-Informationen

Detailed Description:

This clinical trial employs an open label, single arm, multi-center design with primary

analysis testing overall response rate ( ORR), including one interim analysis for futility

and one interim analysis for efficacy.

The trial population includes adult patients with relapsed and refractory multiple myeloma

(MM) after failure of 3 or more lines of therapy, including failing an immunomodulatory drug

(IMiD), a proteasome inhibitor (PI) and an anti-CD38 (cluster of differentiation 38)

monoclonal antibody (mAb) and who have measurable disease at enrollment per IMWG criteria .

In addition, patients must be refractory to the last line of therapy

The trial will enroll 90 efficacy evaluable adult patients with relapsed and refractory MM

(efficacy evaluable means participants infused with a PHE885 product at target dose 10e6 that

met all release specifications).

Patients will be followed for acute and intermediate safety and efficacy within this trial

for a minimum of 2 years before being transferred to the long-term follow-up trial. A

long-term post-study follow-up for lentiviral vector safety will be offered under a separate

destination protocol for 15 years post injection per health authority guidelines.

Ein-/Ausschlusskriterien

Inclusion Criteria:

1. ≥18 years of age at the time of informed consent form (ICF) signature

2. Adult patients after failure of three or more lines of therapy including an IMiD

(e.g., lenalidomide or pomalidomide), a proteasome inhibitor (e.g., bortezomib,

carfilzomib), and an approved anti-CD38 antibody (e.g., daratumumab, isatuximab), and

who have documented evidence of disease progression (IMWG criteria) 3, Must have

received ≥2 consecutive cycles of treatment for at least three prior regimens unless

deemed refractory to that regimen (i.e., progressive disease as the best response)

4. Must be refractory to the last treatment regimen (defined as progressive disease on or

within 60 days measured from last dose of last regimen).

5. Measurable disease at enrollment as defined by the protocol 6. Eastern Cooperative

Oncology Group (ECOG) performance status that is either 0 or 1 at screening 7. Must have a

leukapheresis material of non-mobilized cells accepted for manufacturing

Exclusion Criteria:

1.Prior administration of a genetically modified cellular product including prior BCMA

CAR-T therapy. 2.Participants who have received prior BCMA -directed bi-specific antibodies

or anti-BCMA antibody drug conjugate.

3. Prior autologous SCT within 3 month or allogenic SCT within 6 months prior to signing

informed consent.

4.Plasma cell (PC) leukemia and other plasmacytoid disorders, other than MM 5.POEMS

syndrome 6.Active central nervous system (CNS) involvement by malignancy 7.Patients with

active neurological autoimmune or inflammatory disorders 8.Inadequate cardiac, renal,

hepatic or hematologic function as defined in the protocol.

Other protocol-defined Inclusion/Exclusion may apply.

Studien-Rationale

Primary outcome:

1. Overall response rate (ORR) per Independent Review Committee (IRC) in Efficacy Analysis Set (Time Frame - 24 Months):
Percentage of patients with best overall response (BOR) of either stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR) according to the International Myeloma Working Group (IMWG) criteria'

Secondary outcome:

1. Key Secondary End point: MRD Negativity rate in Bone Marrow (Time Frame - 24 months):
Evaluate the efficacy of PHE885 with respect to MRD negativity rate in bone marrow measured by next generation sequencing (NGS)

2. Complete response rate (CRR) (Time Frame - 24 Months):
Percentage of patients with BOR of sCR or CR according to the IMWG criteria

3. Time to response (Time Frame - 24 Months):
Time form PHE885 infusion to the date of first documented response (PR or better)

4. Duration of Response (DOR) (Time Frame - 24 Months):
Time from first documented response (PR or better) until relapse or death due to any cause

5. Progression free survival (PFS) (Time Frame - 24 Months):
Time from PHE885 infusion until progression or death due to any cause

6. Time to next anti-myeloma treatment (TTNT) (Time Frame - 24 Months):
Time from PHE885 infusion until start of new anti-myeloma therapy or death due to any cause

7. Overall Survival (OS) (Time Frame - 24 Months):
Time from PHE885 infusion until death due to any cause

8. Durability of Minimal Residual Disease (MRD)negativity (Time Frame - 24 Months):
Time from the start of undetectable MRD to the time of reappearance of detectable MRD

9. Patient Reported Outcomes (PRO): EQ-5D-5L Health Questionnaire (Time Frame - 24 months):
PROs as measured by EuroQoL Group EQ-5D-5L Health Questionnaire is a standardized measure of health status developed by the EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal.

10. Patient Reported Outcomes (PRO): EORTC-QLQ-C30 (Time Frame - 24 months):
PROs as measured by European Organization for Research and Treatment of Cancer Quality-of-Life questionnaire (EORTC-QLQ-C30) Questionnaire will be used as a measure of health-related quality of life.

11. Patient Reported Outcomes (PRO): EORTC-QLQ-MY20 (Time Frame - 24 months):
PROs as measured by EORTC-QLQ-MY20 is a 20-item myeloma module intended for use among patients varying in disease stage and treatment modality.

12. PHE885 manufacturing success rate (Time Frame - 24 Months):
Percentage of enrolled patients for whom PHE885 product was manufactured that met all release specifications

13. Manufacturing turnaround time (Time Frame - 24 months):
Time from pick of cryopreserved material at the clinic or hospital until return to the clinical or hospital

14. Transgene of PHE885 concentrations over time in peripheral blood and bone marrow (Time Frame - 24 Months):
As determined by quantitative polymerase chain reaction (qPCR)

15. Cellular kinetics parameter: Cmax (Time Frame - 24 Months):
The maximum transgene level at Tmax

16. Cellular kinetics parameter: Tmax (Time Frame - 24 Months):
The time to peak transgene level

17. Cellular kinetics parameter: AUC (Time Frame - 24 months):
The Area under the curve of the transgene level

18. Immunogenicity to PHE885 (Time Frame - 24 Months):
Summary of pre-existing and treatment-induced immunogenicity (cellular and humoral) of PHE885

Geprüfte Regime

PHE885:
Intravenous (IV) infusion

Quelle: ClinicalTrials.gov

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