Donor Lymphocyte Infusion After Stem Cell Transplant in Treating Patients With Haematological Cancers (ProT4)
Multicenter Randomized Phase II Study to Evaluate the Efficacy of Prophylactic Transfer of CD4 Lymphocytes After T-cell Depleted Reduced Intensity HLA-Identical Sibling Transplantation for Haematological Cancers
RATIONALE: Giving low doses of chemotherapy, such as fludarabine and melphalan, before a donor stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) that have been treated in the laboratory after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving alemtuzumab before transplant and cyclosporine after transplant, may stop this from happening.
PURPOSE: This randomized phase II trial is studying donor lymphocyte infusion after stem cell transplant in preventing cancer relapse or cancer progression in patients with follicular lymphoma, small lymphocytic non-Hodgkin lymphoma, or chronic lymphocytic leukemia.
調査の概要
詳細な説明
OBJECTIVES:
Primary
- To evaluate the effect of prophylactic transfer of donor CD4 cells after T-cell depleted reduced-intensity HLA-identical sibling transplantation upon the risk of relapse or progression in patients with haematological cancers (e.g. NHL, HL, CLL/PLL, PCM, AML, ALL, MDS or CMML depending on the disease status).
Secondary
- To evaluate the effect of prophylactic transfer of donor CD4 cells upon the risk of graft-versus-host disease (GvHD) in these patients.
- To evaluate the effect of prophylactic transfer of donor CD4 cells upon the rates of conversion to full donor chimerism in peripheral blood in these patients.
- To determine the effect of prophylactic transfer of donor CD4 cells upon immune reconstitution in these patients.
- To evaluate the impact of prophylactic transfer of donor CD4 cells upon non-relapse mortality and overall survival of these patients.
OUTLINE: This is a multicenter study.
Patients receive fludarabine IV, melphalan IV, and alemtuzumab IV as reduced intensity conditioning for T-cell depletion followed by a reduced-intensity HLA-identical sibling stem cell transplantation on day 0. Withdrawal of cyclosporine immunosuppression therapy commence at day 40 with tapering over a period of 3-4 weeks, according to the discretion of the PI. Patients are reassessed between day 70-90 post-transplantation. Patients with stable engraftment, no significant graft-versus-host disease, and no early relapse or progression are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive an allogeneic CD4 donor lymphocyte infusion (DLI) at a dose of 1 x10^6 CD4 cells/kg body weight without any other medication once between day 100-120.
- Arm II: Patients receive no further treatment.
Patients undergo blood sample collection for chimerism studies and translational research.
After completion of study treatment, patients are followed up periodically for 1 years and then annually.
Peer Reviewed and Funded or Endorsed by Bloodwise.
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
-
-
-
Birmingham、イギリス
- Birmingham Heartlands Hospital
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Bristol、イギリス
- Bristol Royal Hospital for Children
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Cambridge、イギリス
- Addenbrooke's Hospital
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Glasgow、イギリス
- Beatson West of Scotland Cancer Centre
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Leeds、イギリス
- St James's University Hospital
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Leicester、イギリス
- Leicester Royal Infirmary
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London、イギリス
- University College Hospital London (UCLH)
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Manchester、イギリス
- Christie Hospital
-
Nottingham、イギリス
- Nottingham City Hospital
-
Sheffield、イギリス
- Royal Hallamshire Hospital
-
Southampton、イギリス
- University Hospitals Southampton
-
-
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
At registration (pre-transplant)
Haematological cancer which can be ONE OF the following:
- Non-Hodgkin's lymphoma (NHL) in CR or PR
- Hodgkin's lymphoma (HL) in CR or PR
- Chronic (Pro-)lymphocytic leukaemia (CLL/PLL) in CR or PR
- Plasma cell myeloma (PCM) in CR, VGPR or PR
- Acute myeloid leukaemia (AML) in CR
- Acute lymphoblastic leukaemia (ALL) in CR
- Myelodysplastic syndrome (MDS) < 10% blasts in bone marrow
- Chronic myelomonocytic leukaemia (CMML) < 10% blasts in bone marrow
- Have undergone disease reassessment within 8 weeks prior to registration
HLA-identical sibling transplant to be performed using one of the following reduced intensity alemtuzumab-containing conditioning regimens:
- Fludarabine-busulphan-alemtuzumab
- Fludarabine-melphalan-alemtuzumab
- BCNU-etoposide-cytarabine-melphalan (BEAM)-alemtuzumab
- CCNU-etoposide-cytarabine-melphalan (LEAM)-alemtuzumab
- Aged ≥18 years, and <70 years
- Written informed consent
Exclusion Criteria
- Women who are pregnant or breast-feeding
- Life expectancy of <8 weeks
- Currently taking part in any other interventional clinical research study (involving any IMP, ATMP or cellular therapy)
- Organ dysfunction: Creatinine >200μmol/l, Bilirubin >50μmol/l, or AST/ALT > 3x ULN
Post-transplant
- Active acute GvHD
- Prior grade II-IV GvHD
- Relapse or progressive disease
- Primary or secondary graft failure
- Other cellular therapies
- Requirement for ongoing immunosuppression
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：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 |
|---|---|
|
他の：CD4 DLI
Patients will receive trial product manipulated CD4 DLI post transplant as trial treatment.
|
Patients will receive CD4 DLI between day 70 to 115 post transplant
|
|
他の：No DLI
Patients will receive no DLI post transplant as trial treatment.
|
Patients will not receive DLI as trial treatment
|
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 |
時間枠 |
|---|---|
|
Progression-free survival at 1 year post-transplant
時間枠：during the study and end of study
|
during the study and end of study
|
二次結果の測定
結果測定 |
時間枠 |
|---|---|
|
Proportion of patients attaining multi-lineage full donor chimerism in peripheral blood
時間枠：End of study
|
End of study
|
|
Incidence of infection requiring inpatient treatment
時間枠：during the study and end of study
|
during the study and end of study
|
|
Rate of reconstitution of T-cell subsets and viral-specific immunity
時間枠：End of study
|
End of study
|
|
Cumulative incidence of non-relapse mortality at 1 year
時間枠：End of study
|
End of study
|
|
Overall survival and non-relapse mortality
時間枠：End of study
|
End of study
|
|
Incidence, grade, or pattern of graft-versus-host disease
時間枠：during the study and end of study
|
during the study and end of study
|
協力者と研究者
捜査官
- 主任研究者：Ronjon Chakraverty, Professor、University College Hospital London; UCL Cancer Institute
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 (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 (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
本研究に関する用語
キーワード
- 非ホジキンリンパ腫
- ホジキンリンパ腫
- ワルデンシュトレームマクログロブリン血症
- ステージ III グレード 1 濾胞性リンパ腫
- ステージ III グレード 2 濾胞性リンパ腫
- ステージ IV グレード 1 濾胞性リンパ腫
- ステージ IV グレード 2 濾胞性リンパ腫
- 骨髄異形成症候群
- 再発性グレード 1 濾胞性リンパ腫
- 再発性グレード 2 濾胞性リンパ腫
- 再発小リンパ球性リンパ腫
- III期小リンパ球性リンパ腫
- IV期小リンパ球性リンパ腫
- 難治性慢性リンパ性白血病
- III期慢性リンパ性白血病
- IV期慢性リンパ性白血病
- 移植片対宿主病
- 急性骨髄性白血病
- Chronic (Pro-)lymphocytic leukaemia
- Plasma cell myeloma
- Acute lymphoblastic leukaemia
- Chronic myelomonocytic leukaemia
追加の関連 MeSH 用語
その他の研究ID番号
- UCL/10/0241
- UCL-10/0241 (その他の識別子：Sponsor)
- LRF-09041 (その他の助成金/資金番号：Leukaemia & Lymphoma Research)
- EU-21081 (その他の識別子)
- CRUK-UCL-PROT4 (その他の識別子：Cancer Research UK & UCL Cancer Trials Centre)
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。