Ex Vivo TCR αβ T Cell Depletion for Graft-Versus-Host Disease Prophylaxis in Mismatched Donor Peripheral Blood Stem Cell Transplantation for Hematologic Malignancies
A Phase 2 Study of Ex Vivo TCR αβ T Cell Depletion for Graft-Versus-Host Disease (GVHD) Prophylaxis in Mismatched Donor Peripheral Blood Stem Cell Transplantation for Hematologic Malignancies
This research study is studying the removal of a subset of white blood cells (called alpha/beta T cells) from the donor product using a cell separation device before the product is transplanted into the participant.
The device used to remove the α/βT cells in this study is:
-CliniMACS® TCR α/β Reagent System
調査の概要
詳細な説明
Patients who receive an allogeneic (using another person as the donor) stem cell transplant (SCT) are at risk for developing graft-versus-host disease (GVHD).
The word "graft" refers to the donor blood cells that you will receive during the transplant. The word "host" refers to the person receiving the cells. GVHD is a complication of transplantation where the donor graft attacks and damages some of the participant's tissues.
GVHD may occur when the T cells (a type of white blood cell that helps protect the body from infection) from the donor react against normal tissues or organs in the body. There are two basic types of GVHD:
- Acute GVHD often occurs early (generally first 3-6 months after SCT) may affect skin, gastrointestinal tract (stomach and intestines) and liver.
- Chronic GVHD often occurs later (Usually after 3-6 months after SCT) and may affect many organs and significantly diminish quality of life.
To confirm the diagnosis of acute or chronic GVHD, the participant may be asked to have a biopsy (a small sample of the participant's tissue to look at under the microscope) of the skin, gut, or, rarely, the liver.
In this research study, the investigator are investigating a pre-transplant intervention aimed to prevent GVHD by processing the donor product with the Miltenyi CliniMACS TCR α/β Reagent System. The Reagent System will remove certain cells (called T-Cell Receptor (TCR) α/β positive T-cells) that are thought to cause GVHD from donor product before it is given to the participant. By selectively removing this specific type of T cells from the donor product, the investigators hope to reduce the risk for GVHD without reducing the efficacy of the transplant.
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.
The FDA (the U.S. Food and Drug Administration) has not approved CliniMACS α/β T cell depletion system for use in the US, but this system is approved by the European Medicines Agency (EMA) and used in Europe
研究の種類
入学 (実際)
段階
- フェーズ2
連絡先と場所
研究場所
-
-
Massachusetts
-
Boston、Massachusetts、アメリカ、02215
- Dana Farber Cancer Institute
-
-
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:
Diagnoses and stage at time of transplant admission:
- Acute leukemia (AML or ALL or MPAL) in first or subsequent remission
- Myelodysplastic syndromes (MDS) with <10% marrow blasts
- Myeloproliferative neoplasm (MPN) with <10% marrow blasts
- CMML with less than 10% marrow blast
- CML accelerated phase or second or subsequent chronic phase
- Non-Hodgkin's lymphoma in PR or CR2 or beyond
- Hodgkin lymphoma in PR or CR2 or beyond
- Age 18-65 years
- Patient has a related or unrelated donor who is 8 or 9 out of 10 match at HLA A, B, C, DRB1 and DQB1, based on allele level typing.
- Patient ECOG performance status 0-2 (Karnofsky ≥60%, see Appendix A)
- Patient deemed to be appropriate candidate for myeloablative conditioning transplantation.
- Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
- Patient with active HIV infection
- Chronic active hepatitis B infection (HepB surface Ag+ or detectable Hep B viral load)
- Prior allogeneic hematopoietic stem cell transplantation
- Impaired cardiac function- ejection fraction < 40%
- Impaired pulmonary function- pretransplant FEV1, DLCO < 50%
Impaired renal function, based on
--Serum creatinine > 2.0 mg/dl
Impaired liver function unrelated to primary disease, based on
--ALT or AST > 3x ULN, or Total Bilirubin > 2.0mg/dl (with exception for known or suspected Gilbert's disease)
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Women who are pregnant or breast feeding. Women of child bearing potential must have a negative serum pregnancy test at study entry.
- Participants who are receiving any other investigational agents are eligible but such agent must be discontinued before admission for HSCT, and if resumption of investigation agent is planned after HSCT, this must be approved by the study PI.
- Participants with known active CNS disease. CNS disease that has been treated is eligible
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 |
|---|---|
|
実験的：TCR α/β Reagent System
|
The Reagent System will remove certain cells (called T-Cell Receptor (TCR) α/β positive T-cells) that are thought to cause GVHD from donor product before it is given to participants
|
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 |
|---|---|---|
|
Number of Participants With Severe Acute GVHD-free Survival
時間枠：100 Days
|
Number of participants with severe acute GVHD-free survival will be assessed at 100 days post-SCT
|
100 Days
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Number of Participants With Grades II-IV Acute GVHD
時間枠：2 years
|
Grades II-IV acute GVHD will be assessed at 2 years post-SCT.
Grade I GVHD is characterized as mild disease, grade II as moderate, grade III as severe, and grade IV as life-threatening.
Higher grades of acute GVHD are associated with worse outcomes.
Acute GVHD will be staged by assessment of clinical manifestations in the skin, gastrointestinal tract, and liver.
|
2 years
|
|
Number of Participants With Chronic GVHD
時間枠：2 years
|
Number of participants with chronic GVHD will be assessed at 2 years post-SCT.
|
2 years
|
|
Number of Participants With GVHD and Relapse Free Survival (GRFS)
時間枠：2 years
|
GRFS will be defined as alive without having experienced grade III-IV acute GVHD, moderate/severe chronic GVHD, or relapse of underlying malignancy.
|
2 years
|
|
Number of Participants With Immunosuppression-free Survival
時間枠：2 years
|
Number of participants with immunosuppression-free survival will be assessed at 2 years post-SCT.
|
2 years
|
|
Number of Participants With Hematologic Recovery
時間枠：2 years
|
Hematologic recovery will be assessed in participants at 2 years post-SCT.
|
2 years
|
|
Number of Participants With Immune Reconstitution
時間枠：2 years
|
Immune reconstitution will be assessed in participants at 2 years post-SCT.
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2 years
|
|
Number of Participants With Disease Relapse
時間枠：2 years
|
Disease relapse will be assessed in participants at 2 years post-SCT.
|
2 years
|
|
Number of Participants With Transplant-related Mortality
時間枠：2 years
|
Participant transplant-related mortality will be assessed at 2 years post-SCT.
|
2 years
|
|
Number of Participants With Organ Toxicity
時間枠：2 years
|
Participant organ toxicity will be assessed at 2 years post-SCT.
|
2 years
|
|
Rates of Infections
時間枠：2 years
|
Participant rate of infections will be assessed at 2 years post-SCT.
|
2 years
|
|
Number of Participants With Relapse-free and Overall Survival
時間枠：2 years
|
Number of participants with relapse-free and overall survival will be assessed at 2 years post-SCT.
|
2 years
|
協力者と研究者
捜査官
- 主任研究者：Vincent T Ho, MD、Dana-Farber Cancer Institute
研究記録日
主要日程の研究
研究開始 (実際)
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 (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
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