Phase 1 Infused Donor T Regulatory Cells in Steroid Dependent/Refractory Chronic GVHD
2021年9月20日 更新者：Laura Johnston
A Phase 1 Safety and Tolerability Study of Infused Donor T Regulatory Cells in Steroid Dependent/Refractory Chronic Graft Versus Host Disease
Chronic graft versus host disease (cGVHD) is a common complication of bone marrow or hematopoietic cell transplant from another person (allogeneic transplant).
This study will determine if subjects with steroid dependent/refractory cGVHD can tolerate infusion of donor regulatory T cells and whether their cGVHD responds to the infusion.
調査の概要
詳細な説明
PRIMARY OBJECTIVES:
Determine the safety and tolerability of donor T regulatory (Treg) cell infusions in subjects with steroid dependent/refractory chronic graft versus host disease.
SECONDARY OBJECTIVES:
- Determine the quantitative blood Treg cell changes following the cell infusions
- Determine clinical efficacy of donor Treg cells as failure-free survival (FFS) defined by the absence of a new immunosuppressive therapy added, non-relapse mortality, and recurrent malignancy at Day 180 after the first Treg infusion
In addition to FFS, the study will measure the change in:
- cGVHD symptom burden measured by the Lee cGVHD Symptom Scale by increase in >7 points
- NIH organ-specific cGVHD scale
- The reduction in daily corticosteroid requirement of prednisone to <=0.25 mg/kg-day at Day 180 after the first Treg infusion
研究の種類
介入
入学 (実際)
14
段階
- フェーズ 1
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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California
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Palo Alto、California、アメリカ、94305
- Stanford University, School of Medicine
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年歳以上 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
Inclusion Criteria:
Steroid dependent/refractory cGVHD defined as:
- Steroid dependent disease: Persistent cGVHD manifestations requiring a glucocorticoid dose >= prednisone 0.25 mg/kg/day (0.5 mg/kg orally [po] every other day) for at least 12 weeks
- Steroid refractory disease: Progressive cGVHD manifestations despite treatment with a glucocorticoid dose >= prednisone 0.5 mg/kg/day (1 mg/kg po every other day) for at least 4 weeks
- Participants must be receiving systemic glucocorticoid therapy for cGVHD; all immunosuppressive therapy may include but not be limited to tacrolimus, sirolimus, CellCept, cyclosporine, and systemic corticosteroid must be at stable doses for 28 days prior to the first cell infusion
Chronic GVHD manifestations that can be followed on physical or laboratory exam; these include but are not necessarily limited to:
- Skin changes
- Oral mucosa changes
- Bronchiolitis obliterans
- Ocular changes
- Karnofsky performance status >= 60
- Serum creatinine =< 2 mg/dL
- Absolute neutrophil count (ANC) > 1 x 10^9/L
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 20 x upper limit of normal (ULN) or
- Total bilirubin =< 10 x ULN
- Allogeneic hematopoietic cell transplant recipient
- Transfusion independent
- Oxygen saturation during exertion is maintained at >= 88% on room air
- Does not have clinically significant, symptomatic uncontrolled heart disease (e.g., unstable angina, congestive heart failure, or uncontrolled hypertension)
- DONOR: Age >= 18 to =< 75 years old
- DONOR: Karnofsky performance status of >= 70% defined by institutional standards
- DONOR: Must be the same sibling donor from whom the recipient's blood and marrow graft was collected for the original allogeneic transplant that is human leukocyte antigen (HLA) 7/8 or 8/8 matched at the HLA-A, B,C, DRB1
- DONOR: Serologies for human immunodeficiency virus (HIV) antigen (Ag), HIV 1 and HIV 2 antibody (Ab), human T-lymphotropic virus type I (HTLV 1) and HTLV 2 Ab, hepatitis B surface antigen (sAg) or polymerase chain reaction positive (PCR+), or hepatitis C Ab or PCR+, Syphilis (Treponema) screen and HIV 1 and hepatitis C by nucleic acid testing (NAT) have been collected prior to apheresis
- DONOR: Female donors of child-bearing potential must have a negative serum or urine beta-human chorionic gonadotropin (HCG) test within three weeks of apheresis
- DONOR: Capable of undergoing leukapheresis, have adequate venous access, and be willing to undergo insertion of a central catheter should leukapheresis via peripheral vein be inadequate
- DONOR: Donor selection will be in compliance with 21 Code of Federal Regulations (CFR) 1271
Exclusion Criteria:
- Original transplant utilized an unrelated donor graft
- Uncontrolled infections that are not responsive to antimicrobial therapy
- Progressive malignant disease, including post-transplant lymphoproliferative disease unresponsive to therapy
- Second malignancy except for skin cancer within the last 5 years
- Received any investigational agent =< 28 days before Treg infusions
- Received filgrastim (GCSF) treatment within one month of enrollment
- Received a donor lymphocyte infusion (DLI) or hematopoietic cell transplantation (HCT) within 3 months of enrollment
- DONOR: Evidence of active infection or viral hepatitis
- DONOR: HIV positive
- DONOR: Pregnant donor
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
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：Regulatory T Cells
Cohort 1 at 1x105 Treg cells/kg, Cohort 2 at 5x105 Treg cells/kg and Cohort 3 at 1.5x106 Treg cells/kg with an extension phase at the MTD (or maximum administered dose if the MTD is not reached).
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他の名前：
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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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The frequency of adverse events related to the donor Treg infusions (e.g., grade III-IV aGVHD by the modified Keystone criteria and grade 3 or higher infusional toxicities graded according to the CTCAE v. 4)
時間枠：Up to day 180
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For infusion-related toxicities, recipients will be monitored for 1 hour after the Treg infusion.
Additional toxicities which may occur during the first 28 days after the Treg infusions will count towards the assessment of safety and tolerability (DLT assessment) (e.g., development of aGVHD).
Acute GVHD will be assessed using the modified Keystone criteria on Days 14, 28, 42, 56, 84 and 180 after the Treg infusion (or if the subject is exhibiting signs of aGVHD in-between study visits).
Dose limiting toxicities are defined in Section 8.
Only toxicities which occur during the first 28 days after the cell infusion will count towards the assessment of DLTs.
A dose of Treg will be considered safe if DLTs occur in only 1/6 or 0/3 members of the cohort during the dose-escalation phase.
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Up to day 180
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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Change in absolute blood Treg levels
時間枠：Baseline to day 42
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The change in Treg cell counts from baseline to post infusion will be depicted in boxplots of both relative proportion and absolute numbers.
Mean log (fold change) and confidence intervals will be calculated.
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Baseline to day 42
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Improvement in Failure Free Survival (FFS) over cGVHD
時間枠：At day 180
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FFS is defined as the absence of a third line therapy (treatment failure).
Estimated by the Kaplan-Meier product-limit method, with standard confidence limits.
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At day 180
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Successful achievement of cGVHD partial response or Complete response by the NIH consensus criteria
時間枠：Up to day 180
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The results will be summarized in tabular form, with confidence intervals for the trinomial proportions. |
Up to day 180
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The ability to reduce steroid requirements to <0.25 mg/kg-day
時間枠：At day 180
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At day 180
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Change in >7 points on the Lee cGVHD Symptom scale relates to improvement in quality of life
時間枠：Baseline to day 180
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A one-sample t-test will be used on the change in scale from baseline to months 1, 3, and 6.
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Baseline to day 180
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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
捜査官
- 主任研究者：Laura Johnston、Stanford University
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始
2013年7月1日
一次修了 (実際)
2017年12月31日
研究の完了 (実際)
2018年7月31日
試験登録日
最初に提出
2013年7月15日
QC基準を満たした最初の提出物
2013年7月25日
最初の投稿 (見積もり)
2013年7月30日
学習記録の更新
投稿された最後の更新 (実際)
2021年9月27日
QC基準を満たした最後の更新が送信されました
2021年9月20日
最終確認日
2021年9月1日
詳しくは
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