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- Klinische proef NCT04795882
A New Study Evaluating the Activity of Modular CAR T for mYeloma (MCARTY)
An Open Label, Phase 1 Study Evaluating the Activity of Modular CAR T for mYeloma
This is a Phase 1 rolling 6 trial design evaluating safety of a novel BCMA Chimeric Antigen Receptor (CAR) alone and of CAR T cells engineered to co-express BCMA CAR and a CD19 CAR in patients with relapsed / refractory Multiple Myeloma.
The study will assess the feasibility of generating these Advanced Therapy Investigational Products (ATIMPs) and the safety of administering the CAR T cells (either BCMA alone or co-expressed with CD19) in patients with relapsed / refractory multiple myeloma.
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
Gedetailleerde beschrijving
This is a Phase 1 rolling 6 trial design evaluating safety of a novel BCMA CAR alone and of CAR T cells engineered to co-express BCMA CAR and a CD19 CAR in patients with triple refractory Multiple Myeloma.
The first 3-6 patients will be treated at the lower dose of BCMA CAR T cells in cohort 1 (50 x 10^6 cells). If the lower dose is deemed tolerable, recruitment into cohort 1 at a higher dose (150 x 10^6 BCMA CAR T cells) and cohort 2 at a dose of 50 x 10^6 BCMA/CD19 cells will begin in parallel.
- If the 50 x 10^6 cells BCMA/CD19 CAR dose in cohort 2 is deemed intolerable, then no further patients will be recruited to cohort 2.
- If both 150 x 10^6 cells BCMA CAR (cohort 1) and 50 x 106 cells BCMA/CD19 CAR (cohort 2) are deemed tolerable then recruitment will begin to a higher BCMA/CD19 CAR dose of 150 x 10^6 cells.
- If 150 x 10^6 cells BCMA CAR is intolerable and 50 x 10^6 cells BCMA/CD19 CAR is tolerable then no further patients will be recruited to cohorts 1 or 2.
A Summary of dosing on trial is outlined below:
Cohort 1 (BCMA CAR-T cells)
- Dose level 1: 50x10^6 BCMA CAR-T cells
- Dose level 2: 150x10^6 BCMA CAR-T cells
Cohort 2 (BCMA/CD19 CAR-T cells)
- Dose level 1: 50x10^6 BCMA/CD19 CAR-T cells
- Dose level 2: 150x10^6 BCMA/CD19 CAR-T cells
Studietype
Inschrijving (Verwacht)
Fase
- Fase 1
Contacten en locaties
Studie Locaties
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County (optional)
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London, County (optional), Verenigd Koninkrijk
- University College London Hospital
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
Inclusion Criteria:
- Age ≥ 18
- Relapsed/Refractory Multiple Myeloma
- Secretory disease: PP≥5g/L and/or sFLC≥100mg/L of involved light chain with abnormal K:L ratio.
- ≥3 prior lines of therapies (including proteasome inhibitor, IMiD, anti CD38 antibody)
- Refractory to last line of therapy (not achieved at least PR and progressed within 60 days of last dose or achieved at least PR but progressed within 6 months of last dose)
- Has previously received or is not suitable for ASCT
- Eastern Cooperative Oncology Group (ECOG) performance status 0/1
- Creatinine Clearance (CrCl)≥60ml/min, Absolute Neutrophil Count (ANC)≥1x10^9/L, Platelets (plt)≥50x10^9/L, Haemoglobin (Hb)≥80 /L, lymphocyte count ≥0.3x10^9/L
- Patients must weigh >30 kg
- Agreement to have a pregnancy test, use adequate contraception (if applicable)
- Written informed consent
Exclusion Criteria:
- Previous diagnosis of systemic light chain amyloidosis
- Prior treatment with investigational or approved gene therapy or cell therapy products or allogenic stem cell transplant will be excluded
Stem cell transplant patients only:
- allogeneic stem cell transplant within 12 months prior to registration into the study
- moderate/ severe chronic GVHD (NIH consensus criteria) requiring immunosuppressive therapy and/or systemic steroids
- Oxygen saturation ≤ 90% on air
- Patients with clinically significant, uncontrolled heart disease or a recent (within 6 months) cardiac event
- Left ventricular ejection fraction < 50% (ECHO or MUGA)
- Corrected QT interval (QTc)>470 ms on ECG
- Uncontrolled cardiac arrhythmia (patients with rate-controlled atrial fibrillation are not excluded)
- History or evidence of deep vein thrombosis or pulmonary embolism requiring ongoing therapeutic anticoagulation at preconditioning
- Chronic renal impairment requiring dialysis, or creatinine clearance <60ml/min
- Patients with significant liver disease: alanine aminotransferase or aspartate aminotransferase ≥3x upper limit normal (ULN), or total bilirubin ≥25umol/L (1.5mg/dL), except in patients with Gilbert's syndrome, or evidence of end-stage liver disease (e.g. ascites, hepatic encephalopathy)
- Patients with any major surgical intervention in the last 3 months, cement augmentation for vertebral collapse is permitted
- Patients with active gastrointestinal bleeding
- Patients with active infectious bacterial or viral disease requiring treatment
- Known active central nervous system involvement of MM. History or presence of clinically relevant central nervous system pathology such as epilepsy, paresis, aphasia, stroke within 3 months prior to enrolment, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, uncontrolled mental illness, or psychosis
- Patients receiving corticosteroids at a dose of >5 mg prednisolone per day (or equivalent) that cannot be discontinued
- Use of rituximab (or rituximab biosimilar) within the last 3 months prior to CAR T-cell infusion
- Active autoimmune disease requiring immunosuppression
- Past or current history of other neoplasms
- Received any radiotherapy within the last 7 days prior to lymphodepletion or leukapheresis. Localised radiation to a single site, e.g. for bone pain is permitted at any time
- Patients with any anti-myeloma therapy within the last 7 days prior to LD or leukapheresis
- Inability to tolerate leucapheresis
- Life expectancy <3 months
- Women who are pregnant or breastfeeding
- Known allergy to albumin or DMSO
For CAR T-cell infusion:
- Active infection requiring systemic anti-microbial therapy, or with temperature more or equal to 38 C within 48 hours before scheduled CAR-T cell infusion
- Requirement for supplementary oxygen at the time of scheduled CAR-T cell infusion
- Clinical deterioration of organ functions (hepatic or renal function) exceeding criteria set at study entry
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Niet-gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
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Experimenteel: Cohort 1: BCMA CAR T cells
Treatment with Advanced Therapy Investigational Product (ATIMP): BCMA CAR T-cells
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Infusion with ATIMP: BCMA CAR T-cells
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Experimenteel: Cohort 2: BCMA/CD19 CAR T cells
Treatment with Advanced Therapy Investigational Product (ATIMP): BCMA/CD19 CAR T-cells
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Infusion with ATIMP: BCMA/CD19 CAR T-cells
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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Toxicity evaluated by the incidence of grade 3-5 toxicity causally related to the Advanced Therapy Investigational Product (ATIMP)
Tijdsspanne: 28 days
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The incidence of grade 3-5 toxicity assessed using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 and the American Society for Transplantation and Cellular Therapy (ASTCT) Cytokine Release Syndrome (CRS) and Neurotoxicity tool
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28 days
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Feasibility of manufacturing CAR T-cells evaluated by the number of therapeutic products generated
Tijdsspanne: 30 days
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Feasibility of generation of CAR T cells as evaluated by the number of therapeutic products generated.
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30 days
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Medewerkers en onderzoekers
Sponsor
Studie record data
Bestudeer belangrijke data
Studie start (Werkelijk)
Primaire voltooiing (Verwacht)
Studie voltooiing (Verwacht)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Werkelijk)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
- Hart-en vaatziekten
- Vaatziekten
- Ziekten van het immuunsysteem
- Neoplasmata per histologisch type
- Neoplasmata
- Lymfoproliferatieve aandoeningen
- Immunoproliferatieve aandoeningen
- Hematologische ziekten
- Hemorragische aandoeningen
- Hemostatische aandoeningen
- Paraproteïnemieën
- Bloed eiwit stoornissen
- Multipel myeloom
- Neoplasmata, plasmacel
Andere studie-ID-nummers
- UCL 129642
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .
Klinische onderzoeken op Multipel myeloom
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University of ArkansasVoltooidMEERDERE MYELOMAVerenigde Staten
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PETHEMA FoundationGlaxoSmithKlineWervingTERUGVALLEN EN/OF REFRACTAIRE MEERDERE MYELOMASpanje
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Mario BoccadoroActief, niet wervend
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Beth Israel Deaconess Medical CenterAmgenVoltooidAML | MDS | CLL | ALLE | CML Chronic Phase, Accelerated Phase, or Blast Crisis | RELAPSED NON-HODGKIN'S OR HODGKIN'S LYMPHOMA | APLASTIC ANEMIA | MEERDERE MYELOMA | MYELOPROLIFERATIVE DISORDER (P Vera, CMML, ET)
Klinische onderzoeken op BCMA CAR T cells
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Zhejiang UniversityYake Biotechnology Ltd.WervingMultipel myeloom | Nieuwe diagnose TumorChina
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Zhejiang UniversityYake Biotechnology Ltd.Nog niet aan het wervenRefractair multipel myeloom | Terugval Multipel MyeloomChina
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Zhejiang UniversityYake Biotechnology Ltd.WervingRefractair multipel myeloom | Terugval Multipel MyeloomChina
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Hrain Biotechnology Co., Ltd.Shanghai Changzheng HospitalWerving
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Hrain Biotechnology Co., Ltd.First Affiliated Hospital of Wenzhou Medical University; Shanghai Changzheng...WervingMultipel myeloomChina
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Zhejiang UniversityYake Biotechnology Ltd.WervingVasculitis | Amyloïdose | Auto-immune hemolytische anemie | GEDICHTEN SyndroomChina
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Southwest Hospital, ChinaOnbekendLymfoom | Leukemie | Multipel myeloomChina
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Ting Chang, MDNog niet aan het werven
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Institute of Hematology & Blood Diseases HospitalWerving
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Chongqing Precision Biotech Co., LtdWervingMultipel myeloom | Multipel myeloom bij terugval | Neoplasma, plasmacelChina