Cyclophosphamide Plus T-Cell Transplantation for Patients With Hematologic Malignancies
Cyclophosphamide Plus Transplantation of Partially HLA-mismatched (Haploidentical), CD8+ T Cell-depleted Peripheral Blood Cells for Patients With Myelodysplastic Syndrome, Acute Myeloid Leukemia, Lymphoma, or Myeloproliferative Disorders
RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of abnormal blood cells, either by killing the cells or by stopping them from dividing. Giving cyclophosphamide together with donor lymphocytes that have been treated in the laboratory may be an effective treatment for myelodysplastic syndromes or myeloproliferative disorders.
PURPOSE: This clinical trial is studying the best dose of donor lymphocytes when given together with cyclophosphamide in treating patients with myelodysplastic syndromes or myeloproliferative disorders.
調査の概要
詳細な説明
OBJECTIVES:
- Determine the maximum tolerated dose of allogeneic CD8-positive T-cell-depleted, haploidentical donor lymphocytes when given after cyclophosphamide in patients with myelodysplastic syndromes or myeloproliferative disorders.
OUTLINE: Patients receive cyclophosphamide on days 1 and 2. Patients then undergo infusion of allogeneic T-cell depleted donor lymphocytes on day 3.
Cohorts of patients receive escalating doses of CD8-positive T-cell-depleted haploidentical donor lymphocytes until the maximum tolerated dose is determined.
PROJECTED ACCRUAL: A total of 44 patients will be accrued for this study.
研究の種類
入学 (実際)
段階
- フェーズ 1
連絡先と場所
研究場所
-
-
Maryland
-
Baltimore、Maryland、アメリカ、21231-2410
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
-
-
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
DISEASE CHARACTERISTICS:
Diagnosis of 1 of the following:
Myelodysplastic syndromes (MDS)
- International Prognostic Scoring System (IPSS) score ≥ intermediate-2
- Chronic myelomonocytic leukemia
- Acute myeloid leukemia arising from MDS
Must have failed or are ineligible for or intolerant to treatment with azacitidine
- Patients with normal marrow cytogenetics or an isolated 5q- abnormality must have failed or are ineligible for or intolerant to treatment with lenalidomide
- Patients who are HLA-DR15-positive must have failed or are ineligible for pharmacologic immunosuppression (e.g., anti-thymocyte globulin, cyclosporine, steroids)
- No presence of cytotoxic antibodies against donor lymphocytes
- No HLA-identical donor available OR ineligible for HLA-identical allogeneic bone marrow transplantation
HLA partially mismatched (haploidentical) related donor available
- First-degree related donor, including half-siblings or first cousins
- Inherited recombinant haplotype from parents allowed if donor shares ≥ 1 HLA antigen at each of the HLA-A, -B, and DR loci
PATIENT CHARACTERISTICS:
- ECOG performance status (PS) 0-1 OR Karnofsky PS 80-100%
- Bilirubin < 3.0 mg/dL
- AST and ALT ≤ 4 times upper limit of normal
- Creatinine < 3.0 mg/dL
- LVEF > 35%
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Recovered from prior therapy
- No prior transfusions from donor
- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) or radiotherapy
- No other concurrent investigational drugs
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：Cyclophosphamide + T cells
Conditioning regimen with cyclophosphamide followed by donor T cells on Day 0.
|
50 mg/kg/day intravenously (IV) on Days -2 and -1.
他の名前：
CD8-depleted T cells given IV on Day 0. Dose levels are as follows (all doses in cells/kg): Dose level 1: 1E5 CD4+ cells and less than 3.2E3 CD8+ cells Dose level 2: 1E6 CD4+ cells and less than 3.2E4 CD8+ cells Dose level 3: 1E7 CD4+ cells and less than 3.2E5 CD8+ cells Dose level 4: 5E7 CD4+ cells and less than 1.6E6 CD8+ cells |
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 |
|---|---|---|
|
Maximum tolerated dose of haploidentical donor lymphocytes
時間枠：60 days
|
Maximum dose in cells per kilogram that did not cause dose-limiting toxicity (defined as grade 3-5 non-hematologic toxicity, death within 60 days related to protocol treatment, aplasia related to treatment, or grade 3-4 graft-vs-host-disease).
|
60 days
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Disease response
時間枠：Up to 6 months
|
Percentage of participants who had a complete remission after protocol treatment.
|
Up to 6 months
|
|
Duration of response
時間枠：Up to 6 months
|
Median length of response (in months) of participants who had a complete remission after protocol treatment.
|
Up to 6 months
|
協力者と研究者
捜査官
- スタディチェア：Yvette L. Kasamon, MD、Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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 (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
- J0551
- P30CA006973 (米国 NIH グラント/契約)
- R21CA121588 (米国 NIH グラント/契約)
- NA_00000901 (その他の識別子：JHMIRB)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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