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.
調査の概要
詳細な説明
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
研究の種類
入学 (予想される)
段階
- フェーズ 1
連絡先と場所
研究場所
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County (optional)
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London、County (optional)、イギリス
- University College London Hospital
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:処理
- 割り当て:非ランダム化
- 介入モデル:並列代入
- マスキング:なし(オープンラベル)
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的: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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実験的: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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この研究は何を測定していますか?
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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Toxicity evaluated by the incidence of grade 3-5 toxicity causally related to the Advanced Therapy Investigational Product (ATIMP)
時間枠: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
時間枠: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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協力者と研究者
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (予想される)
研究の完了 (予想される)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
BCMA CAR T cellsの臨床試験
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Zhejiang UniversityYake Biotechnology Ltd.募集
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Hrain Biotechnology Co., Ltd.Shanghai Changzheng Hospital募集
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Zhejiang UniversityYake Biotechnology Ltd.募集血管炎 | アミロイドーシス | 自己免疫性溶血性貧血 | POEMS症候群中国
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Zhejiang UniversityYake Biotechnology Ltd.まだ募集していません
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Zhejiang UniversityYake Biotechnology Ltd.募集
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Hrain Biotechnology Co., Ltd.First Affiliated Hospital of Wenzhou Medical University; Shanghai Changzheng Hospital募集
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Institute of Hematology & Blood Diseases Hospital募集