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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05172596
Recruitment Status : Recruiting
First Posted : December 29, 2021
Last Update Posted : July 22, 2022
Sponsor:
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 cells, manufactured with a new process. CAR-T cells 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) who failed 3 or more different prior 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 100 efficacy evaluable adult patients with relapsed and refractory MM (efficacy evaluable means participants injected with a PHE885 product 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 : 100 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II, Open Label, Study of PHE885, a B-cell Maturation Antigen (BCMA)-Directed CAR-T Cells in Adult Patients With Relapsed and Refractory Multiple Myeloma
Actual Study Start Date : March 7, 2022
Estimated Primary Completion Date : August 30, 2023
Estimated Study Completion Date : August 29, 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 injection (IV) injection




Primary Outcome Measures :
  1. Overall response rate (ORR) per Independent Review Committee (IRC) [ 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. Complete response rate (CRR) [ Time Frame: 24 Months ]
    Percentage of patients with BOR of sCR or CR according to the IMWG criteria

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

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

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

  5. 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

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

  7. 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.

  8. 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.

  9. 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.

  10. Rate of minimal residual disease (MRD) Negativity [ Time Frame: 24 Months ]
    Percentage of patients who attain MRD negative status defined at sensitivity level of 1 in 10^5 nucleated cells by next generation sequencing (NGS)

  11. Durability of MRD negativity [ Time Frame: 24 Months ]
    Time from the start of undetectable MRD to the time of reappearance of detectable MRD

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

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

  16. Cellular kinetics parameter: Cmax [ Time Frame: 24 Months ]
    The maximum transgene level at Tmax

  17. Cellular kinetics parameter: Tmax [ Time Frame: 24 Months ]
    The time to peak transgene level

  18. Cellular kinetics parameter: AUC [ Time Frame: 24 months ]
    The Area under the curve of the transgene level



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   25 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. ≥18 years of age at the time of informed consent form (ICF) signature
  2. Adult patients with relapsed and refractory multiple myeloma who have received at least 3 prior 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 be refractory to the last treatment regimen (defined as progressive disease on or within 60 days measured from last dose of last regimen).
  4. Measurable disease at enrollment as defined by the protocol
  5. Eastern Cooperative Oncology Group (ECOG) performance status that is either 0 or 1 at screening
  6. 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. Participants who have received prior BCMA -directed bi-speciific antibodies or anti-BCMA antibody drug conjugate.
  2. Prior allogenic stem cell transplantation (SCT) at any time or autologous SCT within 3 months prior to signing informed consent
  3. Plasma cell (PC) leukemia and other plasmacytoid disorders, other than MM
  4. POEMS syndrome
  5. Active central nervous system (CNS) involvement by malignancy
  6. Patients with active neurological auto immune or inflammatory disorders

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


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

Locations
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Australia, Melbourne
Novartis Investigative Site Recruiting
VIC, Melbourne, Australia, 3004
Italy
Novartis Investigative Site Recruiting
Bologna, BO, Italy, 40138
Singapore
Novartis Investigative Site Recruiting
Singapore, Singapore, 119228
Novartis Investigative Site Recruiting
Singapore, Singapore, 169608
Spain
Novartis Investigative Site Recruiting
Salamanca, Castilla Y Leon, Spain, 37007
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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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: July 22, 2022
Last Verified: July 2022
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
BCMA
BCMA-directed
chimeric antigen receptor
CAR-T
PHE885
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases