Study to Assess Compliance With Long-Term Mercaptopurine Treatment in Young Patients With Acute Lymphoblastic Leukemia in Remission

NCT ID: NCT00268528

Last Updated: 2020-07-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

720 participants

Study Classification

OBSERVATIONAL

Study Start Date

2005-05-30

Study Completion Date

2020-06-30

Brief Summary

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This clinical trial is assessing compliance with long-term mercaptopurine treatment in young patients with acute lymphoblastic leukemia in remission. Assessing why young patients who have acute lymphoblastic leukemia may not take their medications as prescribed may help identify ways to assist them in taking their medications more consistently and may improve long-term treatment outcomes.

Detailed Description

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PRIMARY OBJECTIVES:

I. To determine and compare adherence to maintenance mercaptopurine (6-MP) in a cohort of children with acute lymphoblastic leukemia (ALL) from four different ethnic and racial groups (Caucasians, African-Americans, Hispanics, and Asians) receiving maintenance/continuation chemotherapy, using the following assessments: serial red cell 6-MP metabolites (6-thioguanine \[6TGN\] and methyl thioinosine monophosphate \[TIMP\]); frequency of 6-MP dosing using an electronic pill monitoring system (Microelectromechanical Systems \[MEMS\]?); self-report of adherence to 6-MP by questionnaire.

II. To determine the impact of adherence to 6-MP (measured using 6TGN, methyl \[Me\]TIMP, MEMS? and self-report data independently) on event-free-survival (EFS) in the entire cohort, after adjusting for known predictors of disease outcome.

III. Define a critical level of adherence (measured independently by 6TGN, MeTIMP, MEMS?, self-report) that has a significant impact on EFS for the entire cohort.

IV. Describe prevalence of adherence to 6-MP by ethnicity (6TGN, MeTIMP, MEMS?, Self-report).

V. Describe behavioral and socio-demographic predictors of adherence using the questionnaire data.

VI. Describe the pill-taking practices in this cohort using the MEMS? data. VII. To evaluate the impact of adherence on ethnic/racial difference in EFS.

SECONDARY OBJECTIVES:

I. To assess the concordance among 6TGN and MeTIMP levels, electronic pill monitoring, and self-reported adherence in the ethnic/racial groups.

OUTLINE:

Patients receive an electronic pill monitoring system comprising an empty MEMS? medication bottle with TrackCap? child resistant (CR). The mercaptopurine prescription is filled using this system. Beginning on day 1 of the third or later course of maintenance therapy, patients take all doses of mercaptopurine from the MEMS? medication bottle with TrackCap? CR for at least 169 days. The MEMS? TrackCap? CR is mailed to the Coordinating Center at the end of study. Patients also receive methotrexate orally (PO) as indicated by their individual chemotherapy regimen.

NOTE: \*Study closed to accrual for Caucasian and Hispanic patients as of 8/14/2009.

After completion of study, patients are followed up every 6 months for 5 years and then annually for up to 10 years.

Conditions

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Childhood Acute Lymphoblastic Leukemia in Remission

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Health service research (electronic pill monitoring system)

Patients receive an electronic pill monitoring system comprising an empty MEMS\^? medication bottle with TrackCap? CR. The mercaptopurine prescription is filled using this system. Beginning on day 1 of the third or later course of maintenance therapy, patients take all doses of mercaptopurine from the MEMS\^? medication bottle with TrackCap? CR for at least 169 days. The MEMS\^? TrackCap? CR is mailed to the Coordinating Center at the end of study. Patients also receive methotrexate PO as indicated by their individual chemotherapy regimen.

Compliance Monitoring

Intervention Type BEHAVIORAL

Receive an electronic pill monitoring system comprising an empty MEMS medication bottle with TrackCap

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Mercaptopurine

Intervention Type DRUG

Given PO

Methotrexate

Intervention Type DRUG

Given PO

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Study of Socioeconomic and Demographic Variables

Intervention Type OTHER

Receive an electronic pill monitoring system comprising an empty MEMS medication bottle with TrackCap

Interventions

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Compliance Monitoring

Receive an electronic pill monitoring system comprising an empty MEMS medication bottle with TrackCap

Intervention Type BEHAVIORAL

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Mercaptopurine

Given PO

Intervention Type DRUG

Methotrexate

Given PO

Intervention Type DRUG

Questionnaire Administration

Ancillary studies

Intervention Type OTHER

Study of Socioeconomic and Demographic Variables

Receive an electronic pill monitoring system comprising an empty MEMS medication bottle with TrackCap

Intervention Type OTHER

Other Intervention Names

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3H-Purine-6-thiol 6 MP 6 Thiohypoxanthine 6 Thiopurine 6-Mercaptopurine 6-Mercaptopurine Monohydrate 6-MP 6-Purinethiol 6-Thiopurine 6-Thioxopurine 6H-Purine-6-thione, 1,7-dihydro- (9CI) 7-Mercapto-1,3,4,6-tetrazaindene Alti-Mercaptopurine Azathiopurine BW 57-323H Flocofil Ismipur Leukerin Leupurin Mercaleukim Mercaleukin Mercaptina Mercaptopurinum Mercapurin Mern NCI-C04886 Puri-Nethol Purimethol Purine, 6-mercapto- Purine-6-thiol (8CI) Purine-6-thiol, monohydrate Purinethiol Purinethol U-4748 WR-2785 Abitrexate Alpha-Methopterin Amethopterin Brimexate CL 14377 CL-14377 Emtexate Emthexat Emthexate Farmitrexat Fauldexato Folex Folex PFS Lantarel Ledertrexate Lumexon Maxtrex Medsatrexate Metex Methoblastin Methotrexate LPF Methotrexate Methylaminopterin Methotrexatum Metotrexato Metrotex Mexate Mexate-AQ MTX Novatrex Rheumatrex Texate Tremetex Trexeron Trixilem WR-19039

Eligibility Criteria

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Inclusion Criteria

* Diagnosis of ALL in first remission, irrespective of risk stratification; enrollment on a Children's Oncology Group (COG) therapeutic study for ALL is not required, but the treatment plan must meet the criteria in this protocol
* Belongs to one of the four following ethnic/racial categories: African-American, Asian, Caucasian, or Hispanic; below please find definitions for these categories

* African-American: includes patients who are African-American or of sub-Saharan black African ancestry
* Asian: patients of Asian ancestry, including the following: Asian Indian (subcontinent), Chinese, Japanese, Korean, Native Hawaiian, Guamanian or Chamorro, Pacific Islander, Filipino, Vietnamese, Samoan, Hmong, Cambodian, Thai, Laotian, or Other Asian races
* Caucasian: includes White or light-skinned patients of European, North African, or Middle Eastern ancestry
* Hispanic: patients of Hispanic ethnicity, including the following: Mexican, Mexican American, Chicano, Cuban, Puerto Rican, or Other Spanish/Hispanic/Latino ethnicity
* Receiving self- or parent/caregiver-administered oral anti-metabolite chemotherapy during the maintenance/continuation phase of therapy; patients are eligible if their treatment plan calls for the following doses of 6-MP and methotrexate (MTX) during the maintenance/continuation phase: 6-MP ? 75 mg/m\^2/day orally; MTX 20 mg/m\^2/week orally;\*\* (modification of 6-MP or MTX dosing based on laboratory or clinical parameters is acceptable)

* For guidance regarding if and when a patient being treated on or according to a specific COG (or legacy group) protocol is eligible, please refer to ?AALL03N1 Eligibility by Protocol Tool,? available in the study data forms packet on the COG website
* Has completed at least 24 weeks of maintenance/continuation chemotherapy, and is scheduled to receive at least 24 more weeks of maintenance/continuation chemotherapy\*\*

* For guidance regarding if and when a patient being treated on or according to a specific COG (or legacy group) protocol is eligible, please refer to ?AALL03N1 Eligibility by Protocol Tool,? available in the study data forms packet on the COG website
* Written informed consent from the patient and/or the patient?s legally authorized guardian, obtained prior to registration and any study-related procedures, and in accordance with institutional policies approved by the United States (U.S) Department of Health and Human Services

Exclusion Criteria

* Patients of multi-ethnic/multi-racial backgrounds are not eligible for this study; while patients of multi-ethnic/multi-racial ancestry (e.g., Caucasian/Japanese, Hawaiian/Puerto Rican) are not eligible, patients of mixed ancestry within a race/ethnicity (e.g., Japanese/Chinese = Asian or Korean/Japanese/Hawaiian = Asian or Mexican/Puerto Rican = Hispanic) may participate as long as they fall under the general classification of "African-American," "Asian," "Caucasian," or "Hispanic"
Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Children's Oncology Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Smita Bhatia

Role: PRINCIPAL_INVESTIGATOR

Children's Oncology Group

Locations

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Children's Hospital of Alabama

Birmingham, Alabama, United States

Site Status

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, United States

Site Status

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

Kaiser Permanente Downey Medical Center

Downey, California, United States

Site Status

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status

Loma Linda University Medical Center

Loma Linda, California, United States

Site Status

Miller Children's and Women's Hospital Long Beach

Long Beach, California, United States

Site Status

Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

Mattel Children's Hospital UCLA

Los Angeles, California, United States

Site Status

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

Valley Children's Hospital

Madera, California, United States

Site Status

Children's Hospital and Research Center at Oakland

Oakland, California, United States

Site Status

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, United States

Site Status

University of California Davis Comprehensive Cancer Center

Sacramento, California, United States

Site Status

Rady Children's Hospital - San Diego

San Diego, California, United States

Site Status

UCSF Medical Center-Parnassus

San Francisco, California, United States

Site Status

Harbor-University of California at Los Angeles Medical Center

Torrance, California, United States

Site Status

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status

University of Connecticut

Farmington, Connecticut, United States

Site Status

Connecticut Children's Medical Center

Hartford, Connecticut, United States

Site Status

Yale University

New Haven, Connecticut, United States

Site Status

Alfred I duPont Hospital for Children

Wilmington, Delaware, United States

Site Status

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, United States

Site Status

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status

Lee Memorial Health System

Fort Myers, Florida, United States

Site Status

University of Florida Health Science Center - Gainesville

Gainesville, Florida, United States

Site Status

Memorial Regional Hospital/Joe DiMaggio Children's Hospital

Hollywood, Florida, United States

Site Status

Nemours Children's Clinic-Jacksonville

Jacksonville, Florida, United States

Site Status

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, United States

Site Status

Miami Cancer Institute

Miami, Florida, United States

Site Status

AdventHealth Orlando

Orlando, Florida, United States

Site Status

Nemours Children's Clinic - Orlando

Orlando, Florida, United States

Site Status

Nemours Children's Clinic - Pensacola

Pensacola, Florida, United States

Site Status

Sacred Heart Hospital

Pensacola, Florida, United States

Site Status

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, United States

Site Status

Saint Joseph's Hospital/Children's Hospital-Tampa

Tampa, Florida, United States

Site Status

Children's Healthcare of Atlanta - Egleston

Atlanta, Georgia, United States

Site Status

Augusta University Medical Center

Augusta, Georgia, United States

Site Status

University of Hawaii Cancer Center

Honolulu, Hawaii, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

University of Illinois

Chicago, Illinois, United States

Site Status

Loyola University Medical Center

Maywood, Illinois, United States

Site Status

Advocate Children's Hospital-Oak Lawn

Oak Lawn, Illinois, United States

Site Status

Advocate Lutheran General Hospital

Park Ridge, Illinois, United States

Site Status

Indiana University/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Site Status

Saint Vincent Hospital and Health Care Center

Indianapolis, Indiana, United States

Site Status

Blank Children's Hospital

Des Moines, Iowa, United States

Site Status

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, United States

Site Status

Tulane University Health Sciences Center

New Orleans, Louisiana, United States

Site Status

Children's Hospital New Orleans

New Orleans, Louisiana, United States

Site Status

Eastern Maine Medical Center

Bangor, Maine, United States

Site Status

C S Mott Children's Hospital

Ann Arbor, Michigan, United States

Site Status

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Ascension Saint John Hospital

Detroit, Michigan, United States

Site Status

Hurley Medical Center

Flint, Michigan, United States

Site Status

Helen DeVos Children's Hospital at Spectrum Health

Grand Rapids, Michigan, United States

Site Status

Spectrum Health at Butterworth Campus

Grand Rapids, Michigan, United States

Site Status

Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, United States

Site Status

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

University of Missouri - Ellis Fischel

Columbia, Missouri, United States

Site Status

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

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University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

Nevada Cancer Research Foundation CCOP

Las Vegas, Nevada, United States

Site Status

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Saint Barnabas Medical Center

Livingston, New Jersey, United States

Site Status

Newark Beth Israel Medical Center

Newark, New Jersey, United States

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Saint Joseph's Regional Medical Center

Paterson, New Jersey, United States

Site Status

Overlook Hospital

Summit, New Jersey, United States

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University of New Mexico Cancer Center

Albuquerque, New Mexico, United States

Site Status

Brooklyn Hospital Center

Brooklyn, New York, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

NYU Winthrop Hospital

Mineola, New York, United States

Site Status

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, United States

Site Status

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, United States

Site Status

Stony Brook University Medical Center

Stony Brook, New York, United States

Site Status

State University of New York Upstate Medical University

Syracuse, New York, United States

Site Status

Montefiore Medical Center - Moses Campus

The Bronx, New York, United States

Site Status

New York Medical College

Valhalla, New York, United States

Site Status

Mission Hospital Inc-Memorial Campus

Asheville, North Carolina, United States

Site Status

Novant Health Presbyterian Medical Center

Charlotte, North Carolina, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Site Status

Children's Hospital Medical Center of Akron

Akron, Ohio, United States

Site Status

Rainbow Babies and Childrens Hospital

Cleveland, Ohio, United States

Site Status

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

Dayton Children's Hospital

Dayton, Ohio, United States

Site Status

The Toledo Hospital/Toledo Children's Hospital

Toledo, Ohio, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Natalie Warren Bryant Cancer Center at Saint Francis

Tulsa, Oklahoma, United States

Site Status

Legacy Emanuel Hospital and Health Center

Portland, Oregon, United States

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Lehigh Valley Hospital - Muhlenberg

Bethlehem, Pennsylvania, United States

Site Status

Geisinger Medical Center

Danville, Pennsylvania, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

Prisma Health Richland Hospital

Columbia, South Carolina, United States

Site Status

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota, United States

Site Status

T C Thompson Children's Hospital

Chattanooga, Tennessee, United States

Site Status

East Tennessee Childrens Hospital

Knoxville, Tennessee, United States

Site Status

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Texas Tech University Health Sciences Center-Amarillo

Amarillo, Texas, United States

Site Status

Dell Children's Medical Center of Central Texas

Austin, Texas, United States

Site Status

Driscoll Children's Hospital

Corpus Christi, Texas, United States

Site Status

Medical City Dallas Hospital

Dallas, Texas, United States

Site Status

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, United States

Site Status

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, United States

Site Status

Covenant Children's Hospital

Lubbock, Texas, United States

Site Status

Methodist Children's Hospital of South Texas

San Antonio, Texas, United States

Site Status

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

Scott and White Memorial Hospital

Temple, Texas, United States

Site Status

Primary Children's Hospital

Salt Lake City, Utah, United States

Site Status

University of Vermont and State Agricultural College

Burlington, Vermont, United States

Site Status

Inova Fairfax Hospital

Falls Church, Virginia, United States

Site Status

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, United States

Site Status

Seattle Children's Hospital

Seattle, Washington, United States

Site Status

Providence Sacred Heart Medical Center and Children's Hospital

Spokane, Washington, United States

Site Status

Madigan Army Medical Center

Tacoma, Washington, United States

Site Status

West Virginia University Charleston Division

Charleston, West Virginia, United States

Site Status

Saint Vincent Hospital Cancer Center Green Bay

Green Bay, Wisconsin, United States

Site Status

Marshfield Medical Center-Marshfield

Marshfield, Wisconsin, United States

Site Status

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Princess Margaret Hospital for Children

Perth, Western Australia, Australia

Site Status

University of Alberta Hospital

Edmonton, Alberta, Canada

Site Status

British Columbia Children's Hospital

Vancouver, British Columbia, Canada

Site Status

IWK Health Centre

Halifax, Nova Scotia, Canada

Site Status

Kingston Health Sciences Centre

Kingston, Ontario, Canada

Site Status

Children's Hospital

London, Ontario, Canada

Site Status

Victoria Hospital

London, Ontario, Canada

Site Status

Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

The Montreal Children's Hospital of the MUHC

Montreal, Quebec, Canada

Site Status

Allan Blair Cancer Centre

Regina, Saskatchewan, Canada

Site Status

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, Canada

Site Status

Countries

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United States Australia Canada

References

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Wadhwa A, Chen Y, Hageman L, Hoppmann A, Angiolillo A, Dickens DS, Neglia JP, Ravindranath Y, Ritchey AK, Termuhlen A, Wong FL, Landier W, Bhatia S. Poverty and relapse risk in children with acute lymphoblastic leukemia: a Children's Oncology Group study AALL03N1 report. Blood. 2023 Jul 20;142(3):221-229. doi: 10.1182/blood.2023019631.

Reference Type DERIVED
PMID: 37070673 (View on PubMed)

Yang JJ, Landier W, Yang W, Liu C, Hageman L, Cheng C, Pei D, Chen Y, Crews KR, Kornegay N, Wong FL, Evans WE, Pui CH, Bhatia S, Relling MV. Inherited NUDT15 variant is a genetic determinant of mercaptopurine intolerance in children with acute lymphoblastic leukemia. J Clin Oncol. 2015 Apr 10;33(11):1235-42. doi: 10.1200/JCO.2014.59.4671. Epub 2015 Jan 26.

Reference Type DERIVED
PMID: 25624441 (View on PubMed)

Bhatia S, Landier W, Hageman L, Kim H, Chen Y, Crews KR, Evans WE, Bostrom B, Casillas J, Dickens DS, Maloney KW, Neglia JP, Ravindranath Y, Ritchey AK, Wong FL, Relling MV. 6MP adherence in a multiracial cohort of children with acute lymphoblastic leukemia: a Children's Oncology Group study. Blood. 2014 Oct 9;124(15):2345-53. doi: 10.1182/blood-2014-01-552166. Epub 2014 May 14.

Reference Type DERIVED
PMID: 24829202 (View on PubMed)

Other Identifiers

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NCI-2009-00305

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000459748

Identifier Type: -

Identifier Source: secondary_id

07-462

Identifier Type: -

Identifier Source: secondary_id

AALL03N1

Identifier Type: OTHER

Identifier Source: secondary_id

COG-AALL03N1

Identifier Type: OTHER

Identifier Source: secondary_id

AALL03N1

Identifier Type: OTHER

Identifier Source: secondary_id

R01CA096670

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10CA095861

Identifier Type: NIH

Identifier Source: secondary_id

View Link

AALL03N1

Identifier Type: -

Identifier Source: org_study_id

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