Adoptive Transfer of Haplo-identical DLI for AML and MDS
Safety and Efficacy of Chemotherapy Combined With Adoptive Transfer of Human Leukocyte Antigen (HLA)-Haploidentical Donor Lymphocyte Infusion (DLI) in Older Patients With Righ-Risk Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)
調査の概要
研究の種類
入学 (実際)
段階
- フェーズ2
- フェーズ 1
連絡先と場所
研究場所
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-
North Carolina
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Durham、North Carolina、アメリカ、27710
- Duke University Medical Center
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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:
- Subjects must have their diagnosis of high-risk AML or high-risk MDS confirmed by pathologic review of bone marrow biopsy according to WHO guidelines
Patients will be defined as high risk AML and thus eligible if they meet one or more of the following criteria:
- Secondary AML (from underlying MDS or therapy related)
- Presence of complex cytogenetic abnormalities (3 or more cytogenetic abnormalities), all monosomies, del 5q, del 7q, inv3, t(3;3), t(6;9), t(9;22), abn 11q23 (excluding t(9;11))
- Fms-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) mutation positive
- Age ≥ 65 years given poor outcomes even with favorable cytogenetics
- Patients will be defined as high risk MDS and thus eligible if they have a MD Anderson Comprehensive Cancer MDS Risk Score ≥9
- Subjects must have Eastern Cooperative Oncology Group (ECOG) Performance status of 0,1,or 2; if ECOG 2, they must also have a Charlson comorbidity index of ≤5.
- Subjects must be 55 years of age or older
- Subjects should have a 3-5/6 HLA-matched related haploidentical donor who is evaluated and deemed able to provide DLI.
- Patient should be able to provide informed consent
- Subjects must have a multigated acquisition (MUGA) and /or ECHO or cardiac magnetic resonance imaging (MRI). The required minimum standards include MUGA or ECHO or cardiac MR showing an ejection fraction( EF) of 40%. Those with an EF 40-49% must also have a cardiologist consult and assist with management.
- Pulmonary function tests (PFTs) with diffusing capacity of lung for carbon monoxide (DLCO) are conditional for subjects at the discretion of the physician. The required minimum standards for those who have PFTs include DLCO of 40%. Those with DLCO of 40-49% must have a pulmonologist consult and assist with management.
- Subjects of all genders and races are eligible
Exclusion Criteria:
- Pregnant or lactating women.
- Patients with other major medical or psychiatric illnesses which the treating physician feels could seriously compromise tolerance to this protocol
- Patients with known active central nervous system (CNS) disease
- Patients with acute promyelocytic leukemia (FAB M3)
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：Idarubicin + Cytarabine + DLI
Chemotherapy combined with adoptive transfer of HLA-haploidentical donor lymphocyte infusion (DLI)
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Eligible subjects will receive induction chemotherapy with idarubicin (12 mg/m2 intravenously for 3 days) and cytarabine (100 mg/m2 intravenously for 7 days) starting Day 1 and ending Day 7. Patients 80 years or older will only receive 2 and 5 days of idarubicin and cytarabine respectively starting Day 1 and ending Day 5. Subjects who experience no remission or partial remission will receive a second course of the identical induction chemotherapy. Cytarabine (100 mg/m2 intravenously for 7 days) starting Day 1 and ending Day 7. Patients 80 years or older will only receive 2 and 5 days of idarubicin and cytarabine respectively starting Day 1 and ending Day 5. Subjects who achieve a complete remission (CR) will receive 2 further courses of cytarabine postremission chemotherapy (consolidation) at 1.0 g/m2 for 6 dosages followed by HLA-mismatched DLI after the second consolidation. HLA-mismatched DLI will be administered Day 9, approximately 24-48 hours following completion of chemotherapy at a dose of 1x10^8 cluster of differentiation 3 (CD3+) cells; however, due to logistics of planning infusions with staffing, donor availability, weekends/holidays, etc., it may be necessary to postpone cell infusion up to 96 hours. Given the time constraints presented by the need to start induction chemotherapy as soon as possible, in some cases, it may not be logistically possible to administer cells with induction. In these cases, patients would just receive standard induction chemotherapy and cells would be administered after consolidation 1 in addition to consolidation 2 Subjects who achieve a CR will receive 2 further courses of cytarabine postremission chemotherapy (consolidation) at 1.0 g/m2 for 6 dosages followed by HLA-mismatched DLI after the second consolidation. |
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 Subjects With Unacceptable Toxicity
時間枠：up to 8 weeks after last cell infusion
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Unacceptable toxicity is defined as: i. Grade III or IV acute GVHD (aGVHD) of the gut or liver or Grade IV aGVHD of the skin lasting > 7 days; ii. Grade IV Common Terminology Criteria for Adverse Events (CTCAE) toxicity attributable to DLI (e.g. infusion reaction, as opposed to Grade IV CTCAE toxicity from chemotherapy) and lasting >7 days iii. Treatment-related mortality (TRM) |
up to 8 weeks after last cell infusion
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Disease Free Survival
時間枠：one year following adoptive transfer
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1 year disease free survival rate following adoptive transfer
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one year following adoptive transfer
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Overall Survival
時間枠：2 years after completing therapy
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Number of participants alive 2 years after completing adoptive transfer therapy.
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2 years after completing therapy
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Percentage of Subjects With Acute GVHD
時間枠：8 weeks after last cell infusion
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Grade III or IV aGVHD of the gut or liver or Grade IV aGVHD of the skin lasting > 7 days
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8 weeks after last cell infusion
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Percentage of Subjects With Unacceptable Toxicity
時間枠：8 weeks after the last cell infusion
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Grade IV CTCAE toxicity attributable to DLI (e.g.
infusion reaction, as opposed to Grade IV CTCAE toxicity from chemotherapy) and lasting >7 days, Grade III or IV aGVHD of the gut or liver or Grade IV aGVHD of the skin lasting > 7 days, or death
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8 weeks after the last cell infusion
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Rate of Efficacy
時間枠：2 years after completing therapy
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Efficacy as measured by the number of subjects with a complete remission.
Responses were evaluated according to standard criteria defined by the National Comprehensive Cancer Network Guidelines for AML (www.nccn.org).
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2 years after completing therapy
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Number of Participants With Immune Recovery
時間枠：up to 2 years after completing therapy
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Immune recovery determined by measurements of cytokine profiles, lymphocyte and natural killer (NK) enumeration and flow-based assays, measured prior to induction, prior to each round of consolidation, 8 weeks after the last cycle of consolidation, and every 3 months after treatment for up to 2 years
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up to 2 years after completing therapy
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Number of Days to Hematopoietic Recovery
時間枠：2 years after completion of therapy
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Hematopoietic recovery as measured by the date of the first of three consecutive laboratory values where the absolute neutrophil count (ANC) ≥ 500/μl , the date of the first of three consecutive laboratory values obtained on different days where the platelet count was > 20,000/μl without transfusion.
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2 years after completion of therapy
|
協力者と研究者
スポンサー
捜査官
- 主任研究者：Anthony Sung, MD、Duke University
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
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- Pro00043247
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