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

Primary Purpose

Multiple Myeloma

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
PHE885
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring Multiple myeloma, B-cell maturation antigen, BCMA, BCMA-directed, chimeric antigen receptor, CAR-T, PHE885

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 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 tot hat 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 auto immune or inflammatory disorders

Other protocol-defined Inclusion/Exclusion may apply.

Sites / Locations

  • Stanford University .Recruiting
  • Emory University School of Medicine/Winship Cancer InstituteRecruiting
  • Dana Farber Cancer Institute Main SiteRecruiting
  • Oregon Health and Science UnivRecruiting
  • Thomas Jefferson University .Recruiting
  • Fred Hutch Cancer ResearchRecruiting
  • Novartis Investigative SiteRecruiting
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Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

PHE885

Arm Description

Patients will receive PHE885

Outcomes

Primary Outcome Measures

Overall response rate (ORR) per Independent Review Committee (IRC) in Efficacy Analysis Set
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 Measures

Key Secondary End point: MRD Negativity rate in Bone Marrow
Evaluate the efficacy of PHE885 with respect to MRD negativity rate in bone marrow measured by next generation sequencing (NGS)
Complete response rate (CRR)
Percentage of patients with BOR of sCR or CR according to the IMWG criteria
Time to response
Time form PHE885 infusion to the date of first documented response (PR or better)
Duration of Response (DOR)
Time from first documented response (PR or better) until relapse or death due to any cause
Progression free survival (PFS)
Time from PHE885 infusion until progression or death due to any cause
Time to next anti-myeloma treatment (TTNT)
Time from PHE885 infusion until start of new anti-myeloma therapy or death due to any cause
Overall Survival (OS)
Time from PHE885 infusion until death due to any cause
Durability of Minimal Residual Disease (MRD)negativity
Time from the start of undetectable MRD to the time of reappearance of detectable MRD
Patient Reported Outcomes (PRO): EQ-5D-5L Health Questionnaire
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.
Patient Reported Outcomes (PRO): EORTC-QLQ-C30
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.
Patient Reported Outcomes (PRO): EORTC-QLQ-MY20
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.
PHE885 manufacturing success rate
Percentage of enrolled patients for whom PHE885 product was manufactured that met all release specifications
Manufacturing turnaround time
Time from pick of cryopreserved material at the clinic or hospital until return to the clinical or hospital
Transgene of PHE885 concentrations over time in peripheral blood and bone marrow
As determined by quantitative polymerase chain reaction (qPCR)
Cellular kinetics parameter: Cmax
The maximum transgene level at Tmax
Cellular kinetics parameter: Tmax
The time to peak transgene level
Cellular kinetics parameter: AUC
The Area under the curve of the transgene level
Immunogenicity to PHE885
Summary of pre-existing and treatment-induced immunogenicity (cellular and humoral) of PHE885

Full Information

First Posted
December 22, 2021
Last Updated
September 11, 2023
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT05172596
Brief Title
PHE885 CAR-T Therapy in Adult Participants With Relapsed and Refractory Multiple Myeloma
Official Title
A Phase 2 Study of PHE885, B-cell Maturation Antigen (BCMA)- Directed CAR-T Cells in Adult Participants With Relapsed and Refractory Multiple Myeloma.
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 7, 2022 (Actual)
Primary Completion Date
December 16, 2025 (Anticipated)
Study Completion Date
December 16, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a Phase II study to determine the efficacy and safety of PHE885, a BCMA-directed CAR-T cell therapy, manufactured with a new process. The CAR-T cell therapy will be investigated as a single agent in relapsed and refractory multiple myeloma
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Multiple myeloma, B-cell maturation antigen, BCMA, BCMA-directed, chimeric antigen receptor, CAR-T, PHE885

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
136 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
PHE885
Arm Type
Experimental
Arm Description
Patients will receive PHE885
Intervention Type
Biological
Intervention Name(s)
PHE885
Intervention Description
Intravenous (IV) infusion
Primary Outcome Measure Information:
Title
Overall response rate (ORR) per Independent Review Committee (IRC) in Efficacy Analysis Set
Description
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'
Time Frame
24 Months
Secondary Outcome Measure Information:
Title
Key Secondary End point: MRD Negativity rate in Bone Marrow
Description
Evaluate the efficacy of PHE885 with respect to MRD negativity rate in bone marrow measured by next generation sequencing (NGS)
Time Frame
24 months
Title
Complete response rate (CRR)
Description
Percentage of patients with BOR of sCR or CR according to the IMWG criteria
Time Frame
24 Months
Title
Time to response
Description
Time form PHE885 infusion to the date of first documented response (PR or better)
Time Frame
24 Months
Title
Duration of Response (DOR)
Description
Time from first documented response (PR or better) until relapse or death due to any cause
Time Frame
24 Months
Title
Progression free survival (PFS)
Description
Time from PHE885 infusion until progression or death due to any cause
Time Frame
24 Months
Title
Time to next anti-myeloma treatment (TTNT)
Description
Time from PHE885 infusion until start of new anti-myeloma therapy or death due to any cause
Time Frame
24 Months
Title
Overall Survival (OS)
Description
Time from PHE885 infusion until death due to any cause
Time Frame
24 Months
Title
Durability of Minimal Residual Disease (MRD)negativity
Description
Time from the start of undetectable MRD to the time of reappearance of detectable MRD
Time Frame
24 Months
Title
Patient Reported Outcomes (PRO): EQ-5D-5L Health Questionnaire
Description
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.
Time Frame
24 months
Title
Patient Reported Outcomes (PRO): EORTC-QLQ-C30
Description
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.
Time Frame
24 months
Title
Patient Reported Outcomes (PRO): EORTC-QLQ-MY20
Description
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.
Time Frame
24 months
Title
PHE885 manufacturing success rate
Description
Percentage of enrolled patients for whom PHE885 product was manufactured that met all release specifications
Time Frame
24 Months
Title
Manufacturing turnaround time
Description
Time from pick of cryopreserved material at the clinic or hospital until return to the clinical or hospital
Time Frame
24 months
Title
Transgene of PHE885 concentrations over time in peripheral blood and bone marrow
Description
As determined by quantitative polymerase chain reaction (qPCR)
Time Frame
24 Months
Title
Cellular kinetics parameter: Cmax
Description
The maximum transgene level at Tmax
Time Frame
24 Months
Title
Cellular kinetics parameter: Tmax
Description
The time to peak transgene level
Time Frame
24 Months
Title
Cellular kinetics parameter: AUC
Description
The Area under the curve of the transgene level
Time Frame
24 months
Title
Immunogenicity to PHE885
Description
Summary of pre-existing and treatment-induced immunogenicity (cellular and humoral) of PHE885
Time Frame
24 Months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: ≥18 years of age at the time of informed consent form (ICF) signature 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Pharmaceuticals
Phone
1-888-669-6682
Email
novartis.email@novartis.com
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Pharmaceuticals
Phone
+41613241111
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Stanford University .
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christina Tran
Phone
605-498-6000
Email
Ctran13@stanford.edu
First Name & Middle Initial & Last Name & Degree
Surbhi Sidana
Facility Name
Emory University School of Medicine/Winship Cancer Institute
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Phone
404-778-5747
First Name & Middle Initial & Last Name & Degree
Sagar Lonial
Facility Name
Dana Farber Cancer Institute Main Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Margaret Wickham
Email
margaret_wickham1@dfci.harvard.edu
First Name & Middle Initial & Last Name & Degree
Adam Sperling
Facility Name
Oregon Health and Science Univ
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Denise Lackey
Phone
503-346-7894
Email
lackey@ohsu.edu
First Name & Middle Initial & Last Name & Degree
Andy Chen
Facility Name
Thomas Jefferson University .
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dawn Liberati
Phone
215-503-7517
Email
Dawn.Liberati@jefferson.edu
First Name & Middle Initial & Last Name & Degree
Usama Gergis
Facility Name
Fred Hutch Cancer Research
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gina Simmons
Phone
206-667-5000
Email
gsimmon2@fredhutch.org
First Name & Middle Initial & Last Name & Degree
Rahul Banerjee
Facility Name
Novartis Investigative Site
City
VIC
State/Province
Melbourne
ZIP/Postal Code
3004
Country
Australia
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Camperdown
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Salvador
State/Province
BA
ZIP/Postal Code
41253-190
Country
Brazil
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Sao Paulo
State/Province
SP
ZIP/Postal Code
01323-900
Country
Brazil
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
São Paulo
State/Province
SP
ZIP/Postal Code
01509-900
Country
Brazil
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N2
Country
Canada
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Lille
ZIP/Postal Code
59037
Country
France
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Nantes Cedex 1
ZIP/Postal Code
44093
Country
France
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Paris 10
ZIP/Postal Code
75475
Country
France
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Poitiers
ZIP/Postal Code
86021
Country
France
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Koeln
ZIP/Postal Code
50937
Country
Germany
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Wuerzburg
ZIP/Postal Code
97080
Country
Germany
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Thessaloniki
State/Province
GR
ZIP/Postal Code
570 10
Country
Greece
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Athens
ZIP/Postal Code
106 76
Country
Greece
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Ramat Gan
ZIP/Postal Code
52621
Country
Israel
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Tel Aviv
ZIP/Postal Code
6423906
Country
Israel
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Bologna
State/Province
BO
ZIP/Postal Code
40138
Country
Italy
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20133
Country
Italy
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Nagoya-city
State/Province
Aichi
ZIP/Postal Code
467-8602
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Sapporo city
State/Province
Hokkaido
ZIP/Postal Code
060 8648
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Kyoto-city
State/Province
Kyoto
ZIP/Postal Code
602-8566
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Sendai city
State/Province
Miyagi
ZIP/Postal Code
980 8574
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Riyadh
ZIP/Postal Code
11211
Country
Saudi Arabia
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Singapore
ZIP/Postal Code
119228
Country
Singapore
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Singapore
ZIP/Postal Code
169608
Country
Singapore
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Salamanca
State/Province
Castilla Y Leon
ZIP/Postal Code
37007
Country
Spain
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Pamplona
State/Province
Navarra
ZIP/Postal Code
31008
Country
Spain
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Birmingham
ZIP/Postal Code
B15 2TH
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Glasgow
ZIP/Postal Code
G51 4TF
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. The Trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
IPD Sharing URL
https://www.clinicalstudydatarequest.com

Learn more about this trial

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

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