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

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ClinicalTrials.gov Identifier: NCT05172596
Recruitment Status : Recruiting
First Posted : December 29, 2021
Last Update Posted : March 10, 2023
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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

Condition or disease Intervention/treatment Phase
Multiple Myeloma Biological: PHE885 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 136 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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.
Actual Study Start Date : February 13, 2022
Estimated Primary Completion Date : December 16, 2025
Estimated Study Completion Date : December 16, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: PHE885
Patients will receive PHE885
Biological: PHE885
Intravenous (IV) infusion

Primary Outcome Measures :
  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 Measures :
  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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05172596

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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

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United States, Massachusetts
Dana Farber Cancer Institute Main Site Recruiting
Boston, Massachusetts, United States, 02215
Principal Investigator: Adam Sperling         
United States, Oregon
Oregon Health and Science Univ Recruiting
Portland, Oregon, United States, 97239
Contact: Denise Lackey    503-346-7894    lackey@ohsu.edu   
Principal Investigator: Levanto Schachter         
Australia, Melbourne
Novartis Investigative Site Recruiting
VIC, Melbourne, Australia, 3004
Australia, New South Wales
Novartis Investigative Site Recruiting
Camperdown, New South Wales, Australia, 2050
Novartis Investigative Site Recruiting
Lille, France, 59037
Novartis Investigative Site Recruiting
Nantes Cedex 1, France, 44093
Novartis Investigative Site Recruiting
Paris Cedex 10, France, 75475
Novartis Investigative Site Recruiting
Poitiers, France, 86021
Novartis Investigative Site Recruiting
Hamburg, Germany, 20246
Novartis Investigative Site Recruiting
Heidelberg, Germany, 69120
Novartis Investigative Site Recruiting
Koeln, Germany, 50937
Novartis Investigative Site Recruiting
Thessaloniki, GR, Greece, 570 10
Novartis Investigative Site Recruiting
Ramat Gan, Israel, 52621
Novartis Investigative Site Recruiting
Tel Aviv, Israel, 6423906
Novartis Investigative Site Recruiting
Bologna, BO, Italy, 40138
Novartis Investigative Site Recruiting
Milano, MI, Italy, 20133
Novartis Investigative Site Recruiting
Nagoya-city, Aichi, Japan, 467-8602
Novartis Investigative Site Recruiting
Sapporo city, Hokkaido, Japan, 060 8648
Novartis Investigative Site Recruiting
Kyoto-city, Kyoto, Japan, 602-8566
Novartis Investigative Site Recruiting
Sendai city, Miyagi, Japan, 980 8574
Novartis Investigative Site Recruiting
Singapore, Singapore, 119228
Novartis Investigative Site Recruiting
Singapore, Singapore, 169608
Novartis Investigative Site Recruiting
Salamanca, Castilla Y Leon, Spain, 37007
Novartis Investigative Site Recruiting
Pamplona, Navarra, Spain, 31008
United Kingdom
Novartis Investigative Site Recruiting
Birmingham, United Kingdom, B15 2TH
Novartis Investigative Site Recruiting
Glasgow, United Kingdom, G51 4TF
Novartis Investigative Site Recruiting
Manchester, United Kingdom, M20 4BX
Sponsors and Collaborators
Novartis Pharmaceuticals
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT05172596    
Other Study ID Numbers: CPHE885B12201
2021-003747-22 ( EudraCT Number )
First Posted: December 29, 2021    Key Record Dates
Last Update Posted: March 10, 2023
Last Verified: March 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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

URL: https://www.clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Multiple myeloma
B-cell maturation antigen
chimeric antigen receptor
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases