Laboratory-Treated Lymphocyte Infusion After Haploidentical Donor Stem Cell Transplant
Delayed Infusion of Ex Vivo Anergized Peripheral Blood Mononuclear Cells Following CD34 Selected Peripheral Blood Stem Cell Transplantation From a Haploidentical Donor for Patients With Acute Leukemia and Myelodysplasia
RATIONALE: Giving total-body irradiation and chemotherapy, such as thiotepa and fludarabine, before a donor stem cell transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving methylprednisolone and antithymocyte globulin before transplant and peripheral blood cells that have been treated in the laboratory after transplant may stop this from happening.
PURPOSE: This phase I trial is studying the side effects and best dose of laboratory-treated peripheral blood cell infusion after donor stem cell transplant in treating patients with hematologic cancers or other diseases.
調査の概要
状態
詳細な説明
OBJECTIVES:
Primary
- Establish the feasibility of delayed infusion of ex vivo anergized donor peripheral blood mononuclear cells (PBMC) after CD34 (cluster designation 34)-selected megadose haploidentical hematopoietic stem cell transplantation (HSCT) in patients with hematopoietic cancers or other diseases.
- Determine the feasibility of collecting parental allogeneic stimulator cells to induce anergy to the nonshared donor-recipient haplotype in these patients.
- Determine the feasibility of collecting donor PBMC as a source of T cells for ex vivo anergization.
- Determine the number of transplanted individuals who meet the criteria for proceeding to delayed infusion of ex vivo anergized donor PBMC.
- Establish the safety of delayed infusion of ex vivo anergized donor PBMC by establishing the maximum number of donor T cells that can be infused without unacceptable graft-versus-host disease.
Secondary
- Evaluate, in vitro, the induction and specificity of alloantigen hyporesponsiveness in donor PBMC after ex vivo anergization.
- Assess, in vitro, the function of immune cells engrafted in these patients.
- Assess, in vitro, whether alloantigen hyporesponsive donor T cells are present in these patients.
- Develop, preliminarily, in vitro data on the extent of pathogen-specific immunity and its rate of recovery.
- Describe the patterns of opportunistic infections in these patients.
OUTLINE: This is a multicenter, dose-escalation study of ex vivo anergized allogeneic peripheral blood mononuclear cells (PBMC). Patients who are treated on any dose level except dose level 1 are stratified according to age (under 17 [pediatric] vs 17 and over [adult]).
- Myeloablative conditioning regimen: Patients undergo total-body irradiation twice daily on days -11 to -9. Patients also receive thiotepa IV over 4 hours on days -8 and -7, fludarabine phosphate IV over 30 minutes on days -7 to -3, and anti-thymocyte globulin IV over 8 hours and methylprednisolone IV over 15-30 minutes on days -6 to -3.
- Allogeneic peripheral blood stem cell transplantation (PBSCT): Patients undergo CD34-selected PBSCT on day 0.
- Ex vivo anergized allogeneic PBMC infusion: If cells have engrafted and patients are free of active uncontrolled infection and graft-vs-host disease, patients undergo allogeneic or autologous PBMC infusion on day 35 or 42.
Cohorts of 3-8 patients receive escalating doses of ex vivo anergized allogeneic PBMCs until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 5 or 3 of 8 patients experience dose-limiting toxicity.
After completion of study, patients are followed periodically for 2 years.
PROJECTED ACCRUAL: A total of 40 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
-
-
California
-
Los Angeles、California、アメリカ、90027-0700
- Childrens Hospital Los Angeles
-
-
Florida
-
Gainesville、Florida、アメリカ、32610
- University of Florida Health Science Center - Gainesville
-
-
Massachusetts
-
Boston、Massachusetts、アメリカ、02114
- Massachusetts General Hospital
-
Boston、Massachusetts、アメリカ、02115
- Children's Hospital Boston
-
Boston、Massachusetts、アメリカ、02115
- Dana Farber Cancer Institute
-
-
Texas
-
Houston、Texas、アメリカ、77030-4009
- M. D. Anderson Cancer Center at University of Texas
-
-
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:
Acute lymphocytic leukemia
In ≥ second complete remission (CR), defined as < 5% blasts in bone marrow (BM) and no active extramedullary disease OR in first CR with any of the following high risk features:
- History of induction failure
- Philadelphia chromosome positive
- t(4;11) by cytogenetic analysis
- Any infant with MLL rearrangements on cytogenetic analysis
- No relapse with isolated extramedullary disease after completion of prior treatment
Acute myeloid leukemia
- Failed induction therapy after < 3 courses
In ≥ second CR, defined as < 5% blasts in BM and no active extramedullary disease OR in first CR with any of the following high-risk features:
- History of induction failure = 5q- or monosomy 7 cytogenetic findings
Any of the following myelodysplastic syndromes:
- Refractory anemia (RA) with excess blasts (RAEB) with a high International Prognostic Scoring System (IPSS) score or score of intermediate-1(INT-1) or intermediate-2 (INT-2)
- RAEB in transformation with INT-1, INT-2, or high IPSS score
- RA with INT-2 score
Patients must have a healthy, related donor who is at least genotypically HLA-A, B, C, and DR haploidentical to the patient
- No suitably matched family donor defined by genotypic or phenotypic identity for ≥ 5/6 A, B, or DR loci
- No immediately available genotypically matched (6/6) unrelated marrow donor
- No immediately available umbilical cord blood donor with suitable cell dose after a search ≥ 2 months
- Patients whose medical condition is at high risk of deteriorating or whose disease is at high risk of progression during a donor search are eligible
- Has a parent with a haplotype that is disparate from that of the donor for the haplotype shared by the patient and parent, but not shared by the patient and donor OR patient is able to donate sufficient autologous cells by peripheral blood draw or unstimulated leukapheresis
- No active CNS disease
PATIENT CHARACTERISTICS:
- Room air O_2 saturation > 95% unless the lungs are involved with disease
- No clinical evidence of pulmonary insufficiency unless the lungs are involved with disease
- AST and ALT < 3 times upper limit of normal (ULN)*
- Bilirubin < 2.0 mg/dL*
- Creatinine < 2 times ULN OR creatinine clearance or glomerular filtration rate > 50% of the lower limit of normal
- LVEF > 45% OR shortening fraction > 20%
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No active infection, defined as absence of an infectious diagnosis or (in patients who have had a recent positive infectious diagnosis) the resolution of fever, documentation of negative cultures or antigen testing, continuation or completion of a course of appropriate therapy, and presence of stable to resolving clinical symptoms
- No evidence of HIV infection OR known HIV positivity NOTE: *Does not apply if liver is involved with disease
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior stem cell transplantation
- No other concurrent immunosuppressive therapy
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:administration of adoptive donor lymphocyte infusion
administration of donor lymphocytes made using costimulatory blockade ex vivo
|
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 |
---|---|---|
Feasibility of making and administering the adoptive T cell product
時間枠:from conditioning through administration of anergized cells on day 35-42
|
ability to collect sufficient cells, make anergized product with good viability, without contamination and infuse per study toxicity of the conditioning regimen, the likelihood of engraftment, and the subsequent percentage of individuals who would be eligible to receive aDLI were determined.
|
from conditioning through administration of anergized cells on day 35-42
|
Safety of administering the adoptive T cell product on day 35-42 post haploidentical transplant
時間枠:the period from aDLI infusion through D100
|
rates of graft failure with CD34 selected product, adverse and severe adverse reactions attributable to infusion of anergized donor cells, including fever, hypotension, acute graft vs host disease, organ dysfunction
|
the period from aDLI infusion through D100
|
Alloreactivity engendered by administering the adoptive T cell product
時間枠:from cell infusion through day 100
|
occurrence and severity of acute GVHD
|
from cell infusion through day 100
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Efficacy in restoring adaptive immunity
時間枠:from aDLI thorough 1 year
|
incidence of viral infection and type of immune reconstitution by phenotype and function of T cells
|
from aDLI thorough 1 year
|
協力者と研究者
捜査官
- スタディチェア:Eva Guinan, MD、Dana-Farber 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 (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
キーワード
- 不応性貧血
- 過剰な芽球を伴う難治性貧血
- 形質転換中の過剰な芽球を伴う難治性貧血
- de novo 骨髄異形成症候群
- 以前に治療された骨髄異形成症候群
- 二次性骨髄異形成症候群
- 11q23 (MLL) 異常を伴う成人急性骨髄性白血病
- inv(16)(p13;q22)を伴う成人急性骨髄性白血病
- t(15;17)(q22;q12)を伴う成人急性骨髄性白血病
- t(16;16)(p13;q22)を伴う成人急性骨髄性白血病
- t(8;21)(q22;q22)を伴う成人急性骨髄性白血病
- 続発性急性骨髄性白血病
- 寛解期の小児急性リンパ芽球性白血病
- 寛解期の小児急性骨髄性白血病
- 小児骨髄異形成症候群
- 寛解期の成人急性骨髄性白血病
- 寛解期の成人急性リンパ芽球性白血病
追加の関連 MeSH 用語
その他の研究ID番号
- 05-030
- P30CA006516 (米国 NIH グラント/契約)
- P01CA100265 (米国 NIH グラント/契約)
- MDA-2005-0695
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?
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。
メチルプレドニゾロンの臨床試験
-
Karolinska Institutet完了
-
Barbara Ann Karmanos Cancer InstituteNational Cancer Institute (NCI)募集びまん性大細胞型B細胞リンパ腫 | 高悪性度B細胞リンパ腫 | 二重発現リンパ腫 | MYCおよびBCL2またはBCL6再構成を伴う高悪性度B細胞リンパ腫 | MYC、BCL2、および BCL6 再構成を伴う高悪性度 B 細胞性リンパ腫アメリカ