Pilot Study of Non-Viral, RNA-Redirected Autologous T Cells in Patients With Refractory or Relapsed Hodgkin Lymphoma
Pilot Study of Non-Viral, RNA-Redirected Autologous T Cells Engineered to Contain Anti-CD19 Linked to TCR and 4-1BB Signaling Domains in Patients With Refractory or Relapsed Hodgkin Lymphoma
調査の概要
詳細な説明
The study will enroll 10 evaluable patients. Evaluable patients are those who have received at least 1 of the 6 RNA CART19 doses at the protocol-specified level. Important safety data can be collected even if a patient receives only one RNA CART19 dose. Subjects (n = 10) will receive up to six IV doses of 8x105-1.5x106 RNA CART19 cells/kg/dose for subjects<80kg and 1x108 RNA CART19 cells/dose (±20%) for subjects ≥80kg.
The RNA CART19 doses and mid-treatment single dose cyclophosphamide will be administered on Mondays, Wednesdays or Fridays. Dosing can be initiated on any of those days. Subjects will be infused in a staggered fashion at two week intervals; that is, the next subject cannot be infused prior to two weeks since the last infusion of the previous subject.
研究の種類
入学 (実際)
段階
- 初期フェーズ 1
連絡先と場所
研究場所
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Pennsylvania
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Philadelphia、Pennsylvania、アメリカ、19104
- Children's Hospital of Philadelphia
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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:
Male or female subjects with HL with no available curative treatment options (such as autologous SCT) who have a limited prognosis (several months to < 2 year survival) with currently available therapies will be enrolled.
- HL with biopsy-proven relapse or refractory disease who are unresponsive to or intolerant of at least one line of standard salvage therapy;
- Patients must have evaluable disease by radiologic imaging (FDG PET-CT or FDG PET-MRI) within 42 day of enrollment; evaluable includes both assessable and/or measurable disease
- Age 18 to 24 years. Patients ages 22-24 will only be enrolled if they are currently being treated at CHOP or another pediatric facility/oncologist.
- Expected survival > 12 weeks at time of screening
- Adequate organ function defined as:
Renal function defined as:
- Creatinine clearance or radioisotope GFR > 60 mL/min/1.73 m2 OR
- Serum creatinine: < 1.7mg/dL (male subjects) or < 1.4mg/dL (female subjects)
- ALT < 5 times the ULN for age
- Total Bilirubin < 2.0 mg/dl
- Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation > 94% on room air
- Patients with relapsed disease after prior allogeneic SCT (myeloablative or non-myeloablative) will be eligible if they meet all other inclusion criteria and
- Have no active GVHD and require no immunosuppression
- Are more than 6 months from transplant 6) Karnofsky performance status ≥ 50 at screening
- Left Ventricular Shortening Fraction (LVSF) > 28% confirmed by echocardiogram, or Left Ventricular Ejection Fraction (LVEF) > 45% confirmed by echocardiogram or MUGA
- Signed written informed consent must be obtained prior to any study procedures
- Successful T cell test expansion (to be performed as part of inclusion criteria until 3 subjects meet all enrollment criteria)
Exclusion Criteria:
- Pregnant or lactating women. The safety of this therapy on unborn children is not known. Female study participants of reproductive potential must have a negative serum pregnancy test at enrollment. A urine pregnancy test will be performed within 48 hours before the RNA CART19 infusion.
- Uncontrolled active infection.
- Active hepatitis B or hepatitis C infection.
- Any uncontrolled active medical disorder that would preclude participation as outlined.
- HIV infection.
- Patients with known active CNS involvement by malignancy. Patients with prior CNS disease that has been effectively treated will be eligible providing treatment was >4 weeks before enrollment
- Patients in complete remission with no evidence by radiologic imaging of disease.
- History of allergy to murine proteins
- History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).
- Anti-CD20 monoclonal antibody therapy within the last 3 months, or absence of circulating B cells
- Unstable angina and/or myocardial infarction within 6 months prior to screening.
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:なし
- 介入モデル:単一グループの割り当て
- 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:RNA CART19 cells
CD19 RNA redirected autologous T-cells (RNA CART19 cells)
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Subjects will be treated with IV administration of RNA anti-CD19 CAR T cells for a total of six doses over 3 weeks.
The first dose will be administered 1-4 days after infusion of cyclophosphamide 30mg/kg.
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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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Incidence of Treatment-Emergent Adverse Events, defined as NCI CTCAE V4 > Grade 3
時間枠:Month 4 post-CART19 Infusion
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Occurrence of study related adverse events, defined as NCI CTCAE V4 > grade 3 signs/symptoms, laboratory toxicities and clinical events that are possible, likely or definitely related to study treatment at any time from the first cyclophosphamide infusion until Month 4.
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Month 4 post-CART19 Infusion
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協力者と研究者
捜査官
- 主任研究者:Susan Rheingold, MD、Children's Hospital of Philadelphia
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
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 (見積もり)
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
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