- ICH GCP
- 미국 임상 시험 레지스트리
- 임상시험 NCT04301076
성인 T 세포 백혈병-림프종(ATL)에 대한 일반적인 조합 화학요법 치료("EPOCH")에 대한 항암제인 레날리도마이드의 추가 테스트
HTLV 관련 성인 T세포 백혈병-림프종(ATLL)에 대한 레날리도마이드와 EPOCH 화학요법의 병용에 대한 1상 연구
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.
연구 개요
상태
상세 설명
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.
연구 유형
등록 (추정된)
단계
- 1단계
연락처 및 위치
연구 장소
-
-
Georgia
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Atlanta, Georgia, 미국, 30322
- 모병
- Emory University Hospital/Winship Cancer Institute
-
연락하다:
- Site Public Contact
- 전화번호: 404-778-1868
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수석 연구원:
- Pamela B. Allen
-
Atlanta, Georgia, 미국, 30308
- 모병
- Emory University Hospital Midtown
-
연락하다:
- Site Public Contact
- 전화번호: 888-946-7447
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수석 연구원:
- Pamela B. Allen
-
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Missouri
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City of Saint Peters, Missouri, 미국, 63376
- 모병
- Siteman Cancer Center at Saint Peters Hospital
-
연락하다:
- Site Public Contact
- 전화번호: 800-600-3606
- 이메일: info@siteman.wustl.edu
-
수석 연구원:
- Lee Ratner
-
Creve Coeur, Missouri, 미국, 63141
- 모병
- Siteman Cancer Center at West County Hospital
-
연락하다:
- Site Public Contact
- 전화번호: 800-600-3606
- 이메일: info@siteman.wustl.edu
-
수석 연구원:
- Lee Ratner
-
St Louis, Missouri, 미국, 63110
- 모병
- Washington University School of Medicine
-
연락하다:
- Site Public Contact
- 전화번호: 800-600-3606
- 이메일: info@siteman.wustl.edu
-
수석 연구원:
- Lee Ratner
-
St Louis, Missouri, 미국, 63129
- 모병
- Siteman Cancer Center-South County
-
연락하다:
- Site Public Contact
- 전화번호: 800-600-3606
- 이메일: info@siteman.wustl.edu
-
수석 연구원:
- Lee Ratner
-
-
New Jersey
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Basking Ridge, New Jersey, 미국, 07920
- 모병
- Memorial Sloan Kettering Basking Ridge
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수석 연구원:
- Steven M. Horwitz
-
연락하다:
- Site Public Contact
- 전화번호: 212-639-7592
-
Middletown, New Jersey, 미국, 07748
- 모병
- Memorial Sloan Kettering Monmouth
-
수석 연구원:
- Steven M. Horwitz
-
연락하다:
- Site Public Contact
- 전화번호: 212-639-7592
-
Montvale, New Jersey, 미국, 07645
- 모병
- Memorial Sloan Kettering Bergen
-
수석 연구원:
- Steven M. Horwitz
-
연락하다:
- Site Public Contact
- 전화번호: 212-639-7592
-
-
New York
-
Commack, New York, 미국, 11725
- 모병
- Memorial Sloan Kettering Commack
-
수석 연구원:
- Steven M. Horwitz
-
연락하다:
- Site Public Contact
- 전화번호: 212-639-7592
-
Harrison, New York, 미국, 10604
- 모병
- Memorial Sloan Kettering Westchester
-
수석 연구원:
- Steven M. Horwitz
-
연락하다:
- Site Public Contact
- 전화번호: 212-639-7592
-
Mineola, New York, 미국, 11501
- 정지된
- NYU Langone Hospital - Long Island
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New York, New York, 미국, 10032
- 모병
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
-
수석 연구원:
- Jennifer E. Amengual
-
연락하다:
- Site Public Contact
- 전화번호: 212-342-5162
- 이메일: cancerclinicaltrials@cumc.columbia.edu
-
New York, New York, 미국, 10065
- 모병
- Memorial Sloan Kettering Cancer Center
-
수석 연구원:
- Steven M. Horwitz
-
연락하다:
- Site Public Contact
- 전화번호: 212-639-7592
-
New York, New York, 미국, 10065
- 정지된
- NYP/Weill Cornell Medical Center
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New York, New York, 미국, 10016
- 정지된
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
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Uniondale, New York, 미국, 11553
- 모병
- Memorial Sloan Kettering Nassau
-
수석 연구원:
- Steven M. Horwitz
-
연락하다:
- Site Public Contact
- 전화번호: 212-639-7592
-
-
Ohio
-
Columbus, Ohio, 미국, 43210
- 모병
- Ohio State University Comprehensive Cancer Center
-
연락하다:
- Site Public Contact
- 전화번호: 800-293-5066
- 이메일: Jamesline@osumc.edu
-
수석 연구원:
- Jonathan E. Brammer
-
-
Virginia
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Richmond, Virginia, 미국, 23298
- 모병
- VCU Massey Comprehensive Cancer Center
-
수석 연구원:
- Bruce O. Hough
-
연락하다:
- Site Public Contact
- 전화번호: 804-628-6430
- 이메일: CTOclinops@vcu.edu
-
-
참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
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
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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
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Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
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Absolute neutrophil count >= 1,000/mm^3 unless decreased due to bone marrow (BM) involvement with lymphoma
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Platelets >= 100,000/mm^3 unless decreased due to BM involvement with lymphoma
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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
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Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
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For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
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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
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
실험적: Treatment (lenalidomide, EPOCH)
See Detailed Description. |
Given IV
다른 이름들:
Given IV
다른 이름들:
Given PO
다른 이름들:
Given PO
다른 이름들:
Undergo bone marrow biopsy
다른 이름들:
Given IV
다른 이름들:
Undergo ECHO
다른 이름들:
Undergo MUGA
다른 이름들:
Given IV
다른 이름들:
Undergo PET/CT
다른 이름들:
Undergo PET/CT or CT
다른 이름들:
Undergo tissue and blood sample collection
다른 이름들:
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Maximum tolerated dose (MTD)
기간: 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
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Overall response rate
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
|
공동 작업자 및 조사자
수사관
- 수석 연구원: Lee Ratner, Yale University Cancer Center LAO
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
- 신생물
- 면역계 질환
- 감염
- RNA 바이러스 감염
- 바이러스 질환
- 조직학적 유형에 따른 신생물
- 혈액 질환
- 레트로바이러스과 감염
- 면역 결핍 증후군
- 림프계 질환
- 림프 증식 장애
- 면역증식성 장애
- 백혈병, 림프
- 백혈병
- 델타레트로바이러스 감염
- 전구 세포 림프구성 백혈병-림프종
- 헴 및 림프병
- 림프종
- 전구체 T세포 림프구성 백혈병-림프종
- HTLV-I 감염
- 유기 화학 물질
- 이종 사이 클릭 화합물, 1- 링
- 이종 사이 클릭 화합물
- 이종 사이 클릭 화합물, 2- 링
- 이종 사이 클릭 화합물, 융합 링
- 조사 기술
- 임상 실험실 기술
- 진단 기술 및 절차
- 진단
- 수술 절차, 수술
- 세포 학적 기술
- 세포 진단
- 탄화수소
- 탄화수소, 순환
- 탄수화물
- 카르 복실 산
- 알칼로이드
- Podophyllotoxin
- 테트라 하이드로 나프탈렌
- 나프탈렌
- 다 환식 방향족 탄화수소
- 탄화수소, 방향족
- 다 환식 화합물
- 글루코 시드
- 글리코 사이드
- 파이퍼 리딘
- 인돌
- Pretadienes
- 임신
- 스테로이드
- 융합 링 화합물
- 진단 기술, 수술
- 화학 기술, 분석
- 스펙트럼 분석
- 포스 포 아미드 머스타드
- 질소 머스타드 화합물
- 겨자 화합물
- 탄화수소, 할로겐화
- 포스 포 아미드
- 유기 인 화합물
- Pregnadienediols
- Vinca 알칼로이드
- Secologanin Tryptamine 알칼로이드
- 인돌 알칼로이드
- 인돌리 지딘
- 인도인
- 안트라 사이클린
- 나프 타센
- 아미노 글리코 시드
- Daunorubicin
- 프탈리 미드
- 프탈산
- 산, 카르 보 사이 클릭
- 파이퍼리돈
- Isoindoles
- 레날리도마이드
- 프레드니손
- 시클로포스파미드
- 에토포시드
- 독소루비신
- 빈크리스틴
- 생검
- 시편 처리
- 자기 공명 분광법
- Deltacortene
- 프레드 닐리 덴
기타 연구 ID 번호
- NCI-2020-01535
- UM1CA186689 (미국 NIH 보조금/계약)
- NCI-2020-01535 (레지스트리 식별자: CTRP (Clinical Trial Reporting Program))
- 10335 (기타 식별자: CTEP)
- UM1CA186704 (미국 NIH 보조금/계약)
- 10335 (기타 식별자: Yale University Cancer Center LAO)
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
IPD 계획 설명
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.
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
미국에서 제조되어 미국에서 수출되는 제품
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .