成人T細胞白血病リンパ腫（ATL）に対する通常の併用化学療法（「EPOCH」）への抗がん剤レナリドマイドの追加の試験
HTLV関連成人T細胞白血病リンパ腫（ATLL）に対するEPOCH化学療法と組み合わせたレナリドマイドの第1相試験
This phase I trial studies the side effects and best dose of lenalidomide when given together with usual combination chemotherapy (etoposide, prednisone, vincristine sulfate [Oncovin], cyclophosphamide, and doxorubicin hydrochloride [hydroxydaunorubicin hydrochloride], or "EPOCH") in treating adult T-cell leukemia-lymphoma. Lenalidomide may help shrink or slow the growth of adult T-cell leukemia-lymphoma. Drugs used in chemotherapy, such as etoposide, vincristine, cyclophosphamide, and doxorubicin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Anti-inflammatory drugs such as prednisone lower the body's immune response and are used with other drugs in the treatment of some types of cancer. Giving lenalidomide and the usual combination chemotherapy may work better in treating adult T-cell leukemia-lymphoma compared to the usual combination chemotherapy alone.
調査の概要
状態
詳細な説明
PRIMARY OBJECTIVE:
I. To determine the safest and most tolerable dose and schedule of lenalidomide to combine with etoposide, prednisone, vincristine sulfate (Oncovin), cyclophosphamide, and doxorubicin hydrochloride (hydroxydaunorubicin hydrochloride) (EPOCH) chemotherapy in adult T-cell leukemia-lymphoma (ATL/ATLL).
SECONDARY OBJECTIVES:
I. To observe and record anti-tumor activity. II. To determine if lenalidomide and EPOCH activity results in significant improvement in remission rates, duration of remissions, and overall survival (OS) as compared to historical controls.
III. To determine if lenalidomide and EPOCH activity correlates with T-cell receptor (TCR) pathway gene mutational spectrum.
IV. To determine effects of lenalidomide and EPOCH on human T-cell leukemia virus type 1 (HTLV-1) proviral deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) loads.
V. To determine effects of lenalidomide and EPOCH on HTLV-1 clonality.
OUTLINE: This is a dose-escalation study of lenalidomide followed by a dose-expansion study.
INDUCTION THERAPY: Patients receive lenalidomide orally (PO) once daily (QD) on days 1-14 of 21 day cycles or days 1-21 or 1-28 of 28 day cycles. Patients receive doxorubicin hydrochloride intravenously (IV) continuously on days 1-4, vincristine sulfate IV continuously on days 1-4, etoposide IV continuously on days 1-4, prednisone PO on days 1-5, and cyclophosphamide IV over 1-4 hours on day 5. Treatment repeats every 21 or 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Patients with complete response (CR), partial response (PR), or stable disease (SD) may receive up to 2 additional cycles of lenalidomide, doxorubicin hydrochloride, vincristine sulfate, etoposide, prednisone, and cyclophosphamide at the discretion of the investigator and/or up to an additional 2 years of lenalidomide in the absence of disease progression or unacceptable toxicity.
Patients undergo bone marrow biopsy at baseline and as clinically indicated. Patients undergo positron emission tomography/computed tomography (PET/CT) or CT, tissue and blood sample collection throughout the trial and multigated acquistion scan (MUGA) and echocardiogram (ECHO) at screening.
After completion of study treatment, patients are followed up for 2 years from end of induction. Patients who do not continue on lenalidomide maintenance are followed every 3 months for up to 2 years from the end of induction, progression, withdrawal, or until death, whichever occurs first.
研究の種類
入学 (推定)
段階
- フェーズ 1
連絡先と場所
研究場所
-
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Georgia
-
Atlanta、Georgia、アメリカ、30322
- 募集
- Emory University Hospital/Winship Cancer Institute
-
コンタクト：
- Site Public Contact
- 電話番号：404-778-1868
-
主任研究者：
- Pamela B. Allen
-
Atlanta、Georgia、アメリカ、30308
- 募集
- Emory University Hospital Midtown
-
コンタクト：
- Site Public Contact
- 電話番号：888-946-7447
-
主任研究者：
- Pamela B. Allen
-
-
Missouri
-
City of Saint Peters、Missouri、アメリカ、63376
- 募集
- Siteman Cancer Center at Saint Peters Hospital
-
コンタクト：
- Site Public Contact
- 電話番号：800-600-3606
- メール：info@siteman.wustl.edu
-
主任研究者：
- Lee Ratner
-
Creve Coeur、Missouri、アメリカ、63141
- 募集
- Siteman Cancer Center at West County Hospital
-
コンタクト：
- Site Public Contact
- 電話番号：800-600-3606
- メール：info@siteman.wustl.edu
-
主任研究者：
- Lee Ratner
-
St Louis、Missouri、アメリカ、63110
- 募集
- Washington University School of Medicine
-
コンタクト：
- Site Public Contact
- 電話番号：800-600-3606
- メール：info@siteman.wustl.edu
-
主任研究者：
- Lee Ratner
-
St Louis、Missouri、アメリカ、63129
- 募集
- Siteman Cancer Center-South County
-
コンタクト：
- Site Public Contact
- 電話番号：800-600-3606
- メール：info@siteman.wustl.edu
-
主任研究者：
- Lee Ratner
-
-
New Jersey
-
Basking Ridge、New Jersey、アメリカ、07920
- 募集
- Memorial Sloan Kettering Basking Ridge
-
主任研究者：
- Steven M. Horwitz
-
コンタクト：
- Site Public Contact
- 電話番号：212-639-7592
-
Middletown、New Jersey、アメリカ、07748
- 募集
- Memorial Sloan Kettering Monmouth
-
主任研究者：
- Steven M. Horwitz
-
コンタクト：
- Site Public Contact
- 電話番号：212-639-7592
-
Montvale、New Jersey、アメリカ、07645
- 募集
- Memorial Sloan Kettering Bergen
-
主任研究者：
- Steven M. Horwitz
-
コンタクト：
- Site Public Contact
- 電話番号：212-639-7592
-
-
New York
-
Commack、New York、アメリカ、11725
- 募集
- Memorial Sloan Kettering Commack
-
主任研究者：
- Steven M. Horwitz
-
コンタクト：
- Site Public Contact
- 電話番号：212-639-7592
-
Harrison、New York、アメリカ、10604
- 募集
- Memorial Sloan Kettering Westchester
-
主任研究者：
- Steven M. Horwitz
-
コンタクト：
- Site Public Contact
- 電話番号：212-639-7592
-
Mineola、New York、アメリカ、11501
- 一時停止
- NYU Langone Hospital - Long Island
-
New York、New York、アメリカ、10032
- 募集
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
-
主任研究者：
- Jennifer E. Amengual
-
コンタクト：
- Site Public Contact
- 電話番号：212-342-5162
- メール：cancerclinicaltrials@cumc.columbia.edu
-
New York、New York、アメリカ、10065
- 募集
- Memorial Sloan Kettering Cancer Center
-
主任研究者：
- Steven M. Horwitz
-
コンタクト：
- Site Public Contact
- 電話番号：212-639-7592
-
New York、New York、アメリカ、10065
- 一時停止
- NYP/Weill Cornell Medical Center
-
New York、New York、アメリカ、10016
- 一時停止
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
-
Uniondale、New York、アメリカ、11553
- 募集
- Memorial Sloan Kettering Nassau
-
主任研究者：
- Steven M. Horwitz
-
コンタクト：
- Site Public Contact
- 電話番号：212-639-7592
-
-
Ohio
-
Columbus、Ohio、アメリカ、43210
- 募集
- Ohio State University Comprehensive Cancer Center
-
コンタクト：
- Site Public Contact
- 電話番号：800-293-5066
- メール：Jamesline@osumc.edu
-
主任研究者：
- Jonathan E. Brammer
-
-
Virginia
-
Richmond、Virginia、アメリカ、23298
- 募集
- VCU Massey Comprehensive Cancer Center
-
主任研究者：
- Bruce O. Hough
-
コンタクト：
- Site Public Contact
- 電話番号：804-628-6430
- メール：CTOclinops@vcu.edu
-
-
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:
-
Patients must have histologically or cytologically confirmed CD2+, CD3+, or CD4+ acute, lymphoma or poor-risk chronic subtypes of ATLL including previously untreated or previously treated individuals who have received no more than 1 previous cycle of EPOCH, cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP), or cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide (CHOPE)
-
Patients previously treated with azidothymidine (AZT), interferon (IFN), bexarotene, or mogamulizumab are eligible. Patients with stable disease at high risk of relapse from prior non-combination chemotherapy containing treatment are eligible to participate
-
Documentation of HTLV infection by enzyme-linked immunosorbent assay (ELISA) in individuals with confirmation of HTLV-1 infection (by immunoblot or polymerase chain reaction [PCR]) or a consistent clinical picture (including two of three of: 1) CD4+ leukemia or lymphoma, 2) hypercalcemia, and/or 3) Japanese, Caribbean, or South American birthplace) is required for enrollment. Confirmation of HTLV-1 infection is required to continue the subject on protocol after the first cycle of therapy. Patients will be enrolled based on reports from local or referral labs (e.g., Mayo Clinic or LabCorp). Confirmation will be performed by Ratner Lab at Washington University, retrospectively, but this is not a Clinical Laboratory Improvement Amendments (CLIA) assay and is not reimbursed by insurance
-
Age ≥ 18 years
- Because no dosing or adverse event (AE) data are currently available on the use of lenalidomide in combination with EPOCH in patients < 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials
-
Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
-
Absolute neutrophil count >= 1,000/mm^3 unless decreased due to bone marrow (BM) involvement with lymphoma
-
Platelets >= 100,000/mm^3 unless decreased due to BM involvement with lymphoma
-
Total bilirubin =< 1.5 x institutional upper limit of normal (ULN), if potentially due to lymphoma, in the dose-expansion cohort, the first cycle may be given without lenalidomide and if transaminitis and bilirubinemia improves to meet parameters, participant may be enrolled
-
Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2 x institutional ULN, if potentially due to lymphoma, in the dose-expansion cohort, the first cycle may be given without lenalidomide and if transaminitis and bilirubinemia improve to meet parameters, participant may be enrolled
-
Creatinine =< institutional ULN OR glomerular filtration rate (GFR) >= 60 mL/min/1.73 m^2 for participants with creatinine levels above institutional normal
-
Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
-
For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
-
Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
-
Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
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Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy
-
Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
-
Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
-
Patients must have a life expectancy > 12 weeks
-
Patients must have no serious active infection requiring therapy at the time of study entry
-
Patients must not require the concurrent use of chemotherapy, interferon, zidovudine, arsenic, radiation therapy, or other specific anti-tumor therapy, during the course of this study
-
The effects of lenalidomide on the developing human fetus are unknown. Immunodulatory derivative (immunomodulatory imide drug [IMiD]) agents as well as other therapeutic agents used in this trial are known to be teratogenic. Females of child-bearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10-14 days prior to, and again within 24 hours of starting lenalidomide, and must either commit to continued abstinence from heterosexual intercourse or begin two acceptable methods of birth control, one highly effective method and one additional effective method at the same time, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. All patients must be counselled at a minimum of every 28 days about pregnancy precautions and risk of fetal exposure. Should a woman become pregnant or suspect she is pregnant while she or her partner are participating in this study, she should inform her treating physician immediately. FCBP must use adequate contraception for at least 28 days after discontinuation from study. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for at least 28 days after discontinuation from study
-
Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a legally-authorized representative (LAR) and/or family member available will also be eligible
Exclusion Criteria:
- Patients that have received prior IMiDs for treatment of ATLL
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
- Patients who have not recovered to grade 1 or better from AEs due to prior anti-cancer therapy (not including cycle 1 of EPOCH, CHOP, or CHOPE if received off protocol) within 14 days prior to enrollment, with the exception of alopecia
- Patients who are receiving any other investigational agents or have received them within 14 days prior to enrollment
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to lenalidomide or other agents used in study. Anaphylactic reactions including death have been reported with cyclophosphamide. Possible cross-sensitivity with other alkylating agents can occur
- Patients unable to take aspirin or prophylactic doses of low molecular weight heparin or direct oral anticoagulants
- Patients with urinary outflow obstruction (contraindication for cyclophosphamide)
- Patients with any form of demyelinating disease should not be given vincristine sulfate injection
- Patients with uncontrolled intercurrent illness
- Patients with psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women are excluded from this study because lenalidomide is an IMiD agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with lenalidomide, breastfeeding should be discontinued if the mother is treated with lenalidomide. These potential risks may also apply to other agents used in this study
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：Treatment (lenalidomide, EPOCH)
See Detailed Description. |
Given IV
他の名前：
Given IV
他の名前：
Given PO
他の名前：
Given PO
他の名前：
Undergo bone marrow biopsy
他の名前：
Given IV
他の名前：
Undergo ECHO
他の名前：
Undergo MUGA
他の名前：
Given IV
他の名前：
Undergo PET/CT
他の名前：
Undergo PET/CT or CT
他の名前：
Undergo tissue and blood sample collection
他の名前：
|
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 (MTD)
時間枠：Up to the end of induction therapy
|
Will determine the MTD for lenalidomide in combination with etoposide, prednisone, vincristine sulfate (Oncovin), cyclophosphamide, and doxorubicin hydrochloride (hydroxydaunorubicin hydrochloride) (EPOCH) chemotherapy. |
Up to the end of induction therapy
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Overall response rate
時間枠：Up to 2 years after completion of study treatment
|
Will be summarized using descriptive statistics. Binomial proportions and their 95% confidence intervals will be used to estimate the response rates of therapy. |
Up to 2 years after completion of study treatment
|
|
Duration of response
時間枠：From the time measurement criteria are met for complete response or partial response until the first date that recurrent or progressive disease is objectively documented, assessed up to 2 years after completion of study treatment
|
Will be summarized using descriptive statistics. The Kaplan-Meier method will be used to evaluate the response duration. |
From the time measurement criteria are met for complete response or partial response until the first date that recurrent or progressive disease is objectively documented, assessed up to 2 years after completion of study treatment
|
|
Progression-free survival
時間枠：Up to 2 years after completion of study treatment
|
Profession-free survival will be determined by the number of weeks from the time of initiation of therapy until there is evidence of tumor progression by acute T-cell leukemia (ATL) response criteria of Tuskasaki, 2009. |
Up to 2 years after completion of study treatment
|
|
Overall survival
時間枠：Up to 2 years after completion of study treatment
|
Over survival will be determined by the number of week of weeks from the time of initiation of therapy until death. |
Up to 2 years after completion of study treatment
|
|
T-cell receptor pathway gene mutational spectrum
時間枠：Up to 2 years after completion of study treatment
|
T-cell receptor pathway gene mutation will be determined by targeted next-generation sequence after hybridization to specific oligonucleotide capture probes corresponding to the sequence most commonly mutation in ATL as defined by Kataoka et al, 2015. |
Up to 2 years after completion of study treatment
|
|
Human T-cell leukemia virus type 1 (HTLV-1) proviral deoxyribonucleic acid and ribonucleic acid loads
時間枠：Up to 2 years after completion of study treatment
|
Analysis of variance methods will be used to evaluate the effects of treatment and time on the viral load measurements, as well as measurements of viral transcripts. |
Up to 2 years after completion of study treatment
|
|
HTLV-1 clonality
時間枠：Up to 2 years after completion of study treatment
|
HTLV-1 clonality will be determined by next generation sequence analysis of viral integration sites resulting in a distribution of the number of reads for each integration site plotted per integration site, as described by Gillet et al. 2011. |
Up to 2 years after completion of study treatment
|
|
Incidence of toxicities
時間枠：Up to the end of induction therapy
|
The incidence of toxicities will be estimated using the binomial proportion and its 95% confidence interval. |
Up to the end of induction therapy
|
協力者と研究者
捜査官
- 主任研究者：Lee Ratner、Yale University Cancer Center LAO
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
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
本研究に関する用語
追加の関連 MeSH 用語
- 新生物
- 免疫系疾患
- 感染症
- RNAウイルス感染症
- ウイルス病
- 組織型別の新生物
- 血液疾患
- レトロウイルス感染症
- 免疫不全症候群
- リンパ疾患
- リンパ増殖性疾患
- 免疫増殖性疾患
- 白血病、リンパ
- 白血病
- デルタレトロウイルス感染症
- 前駆細胞リンパ芽球性白血病-リンパ腫
- ヘミックおよびリンパ疾患
- リンパ腫
- 前駆T細胞リンパ芽球性白血病-リンパ腫
- HTLV-I感染症
- 有機化学物質
- 複素環化化合物、1リング
- 複素環化化合物
- 複素環化化合物、2リング
- 複素環化化合物、融合リング
- 調査手法
- 臨床検査技術
- 診断技術と手順
- 診断
- 外科的処置、手術
- 細胞学的技術
- 細胞診断
- 炭化水素
- 炭化水素、周期的
- 炭水化物
- カルボン酸
- アルカロイド
- ポドフィロトキシン
- テトラヒドロノフタレン
- ナフタレン
- 多環芳香族炭化水素
- 炭化水素、芳香
- 多環式化合物
- グルコシド
- グリコシド
- ピペリジン
- インドール
- 妊娠
- 妊娠
- ステロイド
- 融合リング化合物
- 診断技術、外科的
- 化学技術、分析
- スペクトル分析
- ホスホルアミドマスタード
- 窒素マスタード化合物
- マスタード化合物
- 炭化水素、ハロゲン化
- ホスホラミド
- 有機リン化合物
- 妊娠した
- ヴィンカアルカロイド
- セコロガニントリプタミンアルカロイド
- インドールアルカロイド
- インドリジジン
- インドリジン
- アントラサイクリン
- ナフテセン
- アミノグリコシド
- ダウノルビシン
- フタリミド
- フタル酸
- 酸、炭素環
- ピペリドン
- イソインドール
- レナリドミド
- プレドニン
- シクロホスファミド
- エトポシド
- ドキソルビシン
- ビンクリスチン
- 生検
- 標本処理
- 磁気共鳴分光法
- デルタコルテン
- プレシリデン
その他の研究ID番号
- NCI-2020-01535
- UM1CA186689 (米国 NIH グラント/契約)
- NCI-2020-01535 (レジストリ識別子：CTRP (Clinical Trial Reporting Program))
- 10335 (その他の識別子：CTEP)
- UM1CA186704 (米国 NIH グラント/契約)
- 10335 (その他の識別子：Yale University Cancer Center LAO)
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?
IPD プランの説明
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
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
米国で製造され、米国から輸出された製品。
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