Studying the Effect of Levocarnitine in Protecting the Liver From Chemotherapy for Leukemia or Lymphoma
Purpose
This phase III trial compares the effect of adding levocarnitine to standard chemotherapy versus (vs.) standard chemotherapy alone in protecting the liver in patients with leukemia or lymphoma. Asparaginase is part of the standard of care chemotherapy for the treatment of acute lymphoblastic leukemia (ALL), lymphoblastic lymphoma (LL), and mixed phenotype acute leukemia (MPAL). However, in adolescent and young adults (AYA) ages 15-39 years, liver toxicity from asparaginase is common and often prevents delivery of planned chemotherapy, thereby potentially compromising outcomes. Some groups of people may also be at higher risk for liver damage due to the presence of fat in the liver even before starting chemotherapy. Patients who are of Japanese descent, Native Hawaiian, Hispanic or Latinx may be at greater risk for liver damage from chemotherapy for this reason. Carnitine is a naturally occurring nutrient that is part of a typical diet and is also made by the body. Carnitine is necessary for metabolism and its deficiency or absence is associated with liver and other organ damage. Levocarnitine is a drug used to provide extra carnitine. Laboratory and real-world usage of the dietary supplement levocarnitine suggests its potential to prevent or reduce liver toxicity from asparaginase. The overall goal of this study is to determine whether adding levocarnitine to standard of care chemotherapy will reduce the chance of developing severe liver damage from asparaginase chemotherapy in ALL, LL and/or MPAL patients.
Conditions
- B Acute Lymphoblastic Leukemia
- B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1
- B Acute Lymphoblastic Leukemia, BCR-ABL1-Like
- Lymphoblastic Lymphoma
- Mixed Phenotype Acute Leukemia
- T Acute Lymphoblastic Leukemia
Eligibility
- Eligible Ages
- Between 15 Years and 40 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- >= 15 and < 40 years at time of diagnosis - Newly diagnosed B-ALL, T-ALL, lymphoblastic lymphoma (LLy), or mixed-phenotype acute leukemia/lymphoma (MPAL) - Note: Philadelphia chromosome (PH)+ and PH-like acute leukemia are eligible (use of tyrosine kinase inhibitors [TKI] or CRLF2- targeted concomitant medication must be documented, if used) - Conjugated bilirubin =< 1.5 x upper limit of normal (ULN) for age, regardless of baseline bilirubin (within 7 days prior to enrollment), and - Serum glutamate pyruvate transaminase (SGPT) (ALT) =< 225 U/L (=< 5x ULN) (within 7 days prior to enrollment), and - Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L and serum glutamic oxaloacetic transaminase (SGOT) (AST) to 50 U/L regardless of baseline - SGOT (AST) =< 250 U/L (=< 5x ULN) (within 7 days prior to enrollment) - Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L and SGOT (AST) to 50 U/L regardless of baseline - For patients receiving ursodiol prior to enrollment, laboratory values must meet above criteria off ursodiol for 7 days - PEDIATRIC PATIENTS (AGE 15-17 years): - A 24-hour urine creatinine clearance >= 30 mL/min/1.73 m^2 (within 7 days prior to enrollment) OR - A glomerular filtration rate (GFR) >= 30 mL/min/1.73 m^2. GFR must be performed using one of the following methods (within 7 days prior to enrollment): - 1. Estimated GFR (eGFR) >= 30 mL/min/1.73 m^2. - An online calculator is available through the National Kidney Foundation at https://www.kidney.org/professionals/kdoqi/gfr_calculatorped - 2. Measured GFR >= 30 mL/min/1.73 m^2 (any age). If measured GFR is used, it must be performed using direct measurement with a nuclear blood sampling method or small molecule clearance method (iothalamate or other molecule per institutional standard). - ADULT PATIENTS (AGE 18 YEARS OR OLDER): Creatinine clearance >= 30 mL/min, as estimated by the Cockcroft and Gault formula or a 24-hour urine collection (within 7 days prior to enrollment). Estimated creatinine clearance is based on actual body weight - An online calculator is available through the National Kidney Foundation at https://www.kidney.org/professionals/kdoqi/gfr_calculatorcoc - Berlin-Frankfurt-Munich (BFM), Children's Oncology Group (COG), or C10403-based Induction regimen and must be inclusive of >= 1 dose of pegaspargase or calaspargase pegol, and - First dose of asparaginase must be planned within the first week of induction therapy, and - Dose of pegaspargase or calaspargase pegol must be >= 1,000 IU/ m^2 (dose-capping permitted per primary regimen) - Note: Co-enrollment on a therapeutic consortia trial is not required - All patients and/or their parents or legal guardians must sign a written informed consent - All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria
- Down syndrome - Known inherited or autoimmune liver disease impacting conjugated bilirubin (e.g., Alagille syndrome, primary sclerosing cholangitis, other) - Known biopsy (or imaging) proven severe liver fibrosis (Batts-Ludwig >= stage 3) - Unable to tolerate oral formulation of study drug at enrollment - Patients who received chemotherapy or treatment for a prior malignancy are not eligible - The following are permitted: steroid prophase, hydroxyurea, or other cytoreduction prior to initiation of Induction chemotherapy (must be documented) and chemotherapy for current diagnosis (i.e. initiation of Induction therapy within enrollment window). Chemotherapy prior to enrollment for treatment of a non-malignancy (e.g., steroid or methotrexate for autoimmune disease) is also permitted and must be documented - Female patients who are pregnant since fetal toxicities and teratogenic effects in humans are unknown for study drug. A pregnancy test is required for female patients of childbearing potential - Lactating females who plan to breastfeed their infants - Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- Parallel with the option to cross over to Arm C to begin levocarnitine rescue
- Primary Purpose
- Supportive Care
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Arm A (levocarnitine, standard of care chemotherapy) |
Patients receive levocarnitine PO or IV as a bolus over 2 to 3 minutes or by infusion (over 10 to 30 minutes or per institutional standard) starting prior to standard of care induction chemotherapy with pegaspargase or calaspargase pegol and continued through the earlier of the last day of Induction phase (i.e., day prior to start of next phase) or Induction day 35. Patients may also undergo blood sample collection during screening and on study. |
|
|
Active Comparator Arm B (standard of care chemotherapy) |
Patients receive standard of care induction chemotherapy with pegaspargase or calaspargase pegol on study. Patients may also undergo blood sample collection during screening and on study. |
|
|
Experimental Arm C (rescue levocarnitine) |
Patients in Arms A and B who develop conjugated hyperbilirubinemia > 3 mg/dL during induction may receive levocarnitine rescue PO or IV as a bolus dose over 2 to 3 minutes or by infusion (over 10 to 30 minutes or per institutional standard) until resolution of conjugated hyperbilirubinemia =< 3 mg/dL (or start of consolidation or the next treatment phase, whichever occurs first). |
|
Recruiting Locations
Providence Alaska Medical Center
Anchorage, Alaska 99508
Anchorage, Alaska 99508
Kingman Regional Medical Center
Kingman, Arizona 86401
Kingman, Arizona 86401
Banner University Medical Center - Tucson
Tucson, Arizona 85719
Tucson, Arizona 85719
Arkansas Children's Hospital
Little Rock, Arkansas 72202-3591
Little Rock, Arkansas 72202-3591
Contact:
Site Public Contact
501-364-7373
Site Public Contact
501-364-7373
Kaiser Permanente-Anaheim
Anaheim, California 92806
Anaheim, California 92806
PCR Oncology
Arroyo Grande, California 93420
Arroyo Grande, California 93420
Kaiser Permanente-Bellflower
Bellflower, California 90706
Bellflower, California 90706
Kaiser Permanente Downey Medical Center
Downey, California 90242
Downey, California 90242
Contact:
Site Public Contact
626-564-3455
Site Public Contact
626-564-3455
City of Hope Comprehensive Cancer Center
Duarte, California 91010
Duarte, California 91010
Kaiser Permanente-Fontana
Fontana, California 92335
Fontana, California 92335
Loma Linda University Medical Center
Loma Linda, California 92354
Loma Linda, California 92354
Contact:
Site Public Contact
909-558-4050
Site Public Contact
909-558-4050
Miller Children's and Women's Hospital Long Beach
Long Beach, California 90806
Long Beach, California 90806
Contact:
Site Public Contact
562-933-5600
Site Public Contact
562-933-5600
Children's Hospital Los Angeles
Los Angeles, California 90027
Los Angeles, California 90027
Contact:
Site Public Contact
323-361-4110
Site Public Contact
323-361-4110
Kaiser Permanente Los Angeles Medical Center
Los Angeles, California 90027
Los Angeles, California 90027
Valley Children's Hospital
Madera, California 93636
Madera, California 93636
UCSF Benioff Children's Hospital Oakland
Oakland, California 94609
Oakland, California 94609
Stanford Cancer Institute Palo Alto
Palo Alto, California 94304
Palo Alto, California 94304
Kaiser Permanente-San Diego Mission
San Diego, California 92108
San Diego, California 92108
Kaiser Permanente-San Diego Zion
San Diego, California 92120
San Diego, California 92120
UCSF Medical Center-Mission Bay
San Francisco, California 94158
San Francisco, California 94158
Children's Hospital Colorado
Aurora, Colorado 80045
Aurora, Colorado 80045
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Denver, Colorado 80218
Denver, Colorado 80218
Alfred I duPont Hospital for Children
Wilmington, Delaware 19803
Wilmington, Delaware 19803
Children's National Medical Center
Washington, District of Columbia 20010
Washington, District of Columbia 20010
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida 33908
Fort Myers, Florida 33908
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
Hollywood, Florida 33021
Hollywood, Florida 33021
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida 32207
Jacksonville, Florida 32207
Miami Cancer Institute
Miami, Florida 33176
Miami, Florida 33176
Contact:
Site Public Contact
786-596-2000
Site Public Contact
786-596-2000
AdventHealth Orlando
Orlando, Florida 32803
Orlando, Florida 32803
Sacred Heart Hospital
Pensacola, Florida 32504
Pensacola, Florida 32504
Tampa General Hospital
Tampa, Florida 33606
Tampa, Florida 33606
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida 33607
Tampa, Florida 33607
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia 30329
Atlanta, Georgia 30329
Memorial Health University Medical Center
Savannah, Georgia 31404
Savannah, Georgia 31404
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii 96826
Honolulu, Hawaii 96826
Contact:
Site Public Contact
808-983-6090
Site Public Contact
808-983-6090
Saint Luke's Cancer Institute - Boise
Boise, Idaho 83712
Boise, Idaho 83712
Northwestern University
Chicago, Illinois 60611
Chicago, Illinois 60611
University of Illinois
Chicago, Illinois 60612
Chicago, Illinois 60612
Contact:
Site Public Contact
312-355-3046
Site Public Contact
312-355-3046
University of Chicago Comprehensive Cancer Center
Chicago, Illinois 60637
Chicago, Illinois 60637
Advocate Children's Hospital-Oak Lawn
Oak Lawn, Illinois 60453
Oak Lawn, Illinois 60453
Contact:
Site Public Contact
847-723-7570
Site Public Contact
847-723-7570
Advocate Children's Hospital-Park Ridge
Park Ridge, Illinois 60068
Park Ridge, Illinois 60068
Southern Illinois University School of Medicine
Springfield, Illinois 62702
Springfield, Illinois 62702
Contact:
Site Public Contact
217-545-7929
Site Public Contact
217-545-7929
Riley Hospital for Children
Indianapolis, Indiana 46202
Indianapolis, Indiana 46202
Contact:
Site Public Contact
800-248-1199
Site Public Contact
800-248-1199
Ascension Saint Vincent Indianapolis Hospital
Indianapolis, Indiana 46260
Indianapolis, Indiana 46260
Blank Children's Hospital
Des Moines, Iowa 50309
Des Moines, Iowa 50309
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa 52242
Iowa City, Iowa 52242
Contact:
Site Public Contact
800-237-1225
Site Public Contact
800-237-1225
University of Kansas Cancer Center
Kansas City, Kansas 66160
Kansas City, Kansas 66160
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas 66205
Westwood, Kansas 66205
University of Kentucky/Markey Cancer Center
Lexington, Kentucky 40536
Lexington, Kentucky 40536
Contact:
Site Public Contact
859-257-3379
Site Public Contact
859-257-3379
Norton Children's Hospital
Louisville, Kentucky 40202
Louisville, Kentucky 40202
Ochsner Medical Center Jefferson
New Orleans, Louisiana 70121
New Orleans, Louisiana 70121
Maine Children's Cancer Program
Scarborough, Maine 04074
Scarborough, Maine 04074
Sinai Hospital of Baltimore
Baltimore, Maryland 21215
Baltimore, Maryland 21215
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland 21287
Baltimore, Maryland 21287
C S Mott Children's Hospital
Ann Arbor, Michigan 48109
Ann Arbor, Michigan 48109
Contact:
Site Public Contact
800-865-1125
Site Public Contact
800-865-1125
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan 48109
Ann Arbor, Michigan 48109
Bronson Battle Creek
Battle Creek, Michigan 49017
Battle Creek, Michigan 49017
Children's Hospital of Michigan
Detroit, Michigan 48201
Detroit, Michigan 48201
Michigan State University Clinical Center
East Lansing, Michigan 48824
East Lansing, Michigan 48824
Contact:
Site Public Contact
517-975-9547
Site Public Contact
517-975-9547
Corewell Health Grand Rapids Hospitals - Butterworth Hospital
Grand Rapids, Michigan 49503
Grand Rapids, Michigan 49503
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan 49503
Grand Rapids, Michigan 49503
Trinity Health Grand Rapids Hospital
Grand Rapids, Michigan 49503
Grand Rapids, Michigan 49503
Bronson Methodist Hospital
Kalamazoo, Michigan 49007
Kalamazoo, Michigan 49007
West Michigan Cancer Center
Kalamazoo, Michigan 49007
Kalamazoo, Michigan 49007
Ascension Borgess Cancer Center
Kalamazoo, Michigan 49009
Kalamazoo, Michigan 49009
Ascension Borgess Hospital
Kalamazoo, Michigan 49048
Kalamazoo, Michigan 49048
Trinity Health Muskegon Hospital
Muskegon, Michigan 49444
Muskegon, Michigan 49444
Corewell Health Lakeland Hospitals - Niles Hospital
Niles, Michigan 49120
Niles, Michigan 49120
Contact:
Site Public Contact
616-391-1230
Site Public Contact
616-391-1230
Cancer and Hematology Centers of Western Michigan - Norton Shores
Norton Shores, Michigan 49444
Norton Shores, Michigan 49444
Corewell Health Reed City Hospital
Reed City, Michigan 49677
Reed City, Michigan 49677
Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
Saint Joseph, Michigan 49085
Saint Joseph, Michigan 49085
Corewell Health Lakeland Hospitals - Saint Joseph Hospital
Saint Joseph, Michigan 49085
Saint Joseph, Michigan 49085
Munson Medical Center
Traverse City, Michigan 49684
Traverse City, Michigan 49684
University of Michigan Health - West
Wyoming, Michigan 49519
Wyoming, Michigan 49519
Mayo Clinic in Rochester
Rochester, Minnesota 55905
Rochester, Minnesota 55905
Contact:
Site Public Contact
855-776-0015
Site Public Contact
855-776-0015
University of Mississippi Medical Center
Jackson, Mississippi 39216
Jackson, Mississippi 39216
Contact:
Site Public Contact
601-815-6700
Site Public Contact
601-815-6700
Children's Mercy Hospitals and Clinics
Kansas City, Missouri 64108
Kansas City, Missouri 64108
Mercy Hospital Saint Louis
Saint Louis, Missouri 63141
Saint Louis, Missouri 63141
Contact:
Site Public Contact
314-251-7066
Site Public Contact
314-251-7066
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska 68114
Omaha, Nebraska 68114
Contact:
Site Public Contact
402-955-3949
Site Public Contact
402-955-3949
University of Nebraska Medical Center
Omaha, Nebraska 68198
Omaha, Nebraska 68198
Carson Tahoe Regional Medical Center
Carson City, Nevada 89703
Carson City, Nevada 89703
Comprehensive Cancer Centers of Nevada - Henderson
Henderson, Nevada 89052
Henderson, Nevada 89052
Comprehensive Cancer Centers of Nevada-Horizon Ridge
Henderson, Nevada 89052
Henderson, Nevada 89052
OptumCare Cancer Care at Seven Hills
Henderson, Nevada 89052
Henderson, Nevada 89052
Comprehensive Cancer Centers of Nevada-Southeast Henderson
Henderson, Nevada 89074
Henderson, Nevada 89074
GenesisCare USA - Henderson
Henderson, Nevada 89074
Henderson, Nevada 89074
Las Vegas Urology - Green Valley
Henderson, Nevada 89074
Henderson, Nevada 89074
Urology Specialists of Nevada - Green Valley
Henderson, Nevada 89074
Henderson, Nevada 89074
OptumCare Cancer Care at Charleston
Las Vegas, Nevada 89102
Las Vegas, Nevada 89102
University Medical Center of Southern Nevada
Las Vegas, Nevada 89102
Las Vegas, Nevada 89102
Hope Cancer Care of Nevada
Las Vegas, Nevada 89103
Las Vegas, Nevada 89103
Radiation Oncology Centers of Nevada Central
Las Vegas, Nevada 89106
Las Vegas, Nevada 89106
Urology Specialists of Nevada - Central
Las Vegas, Nevada 89106
Las Vegas, Nevada 89106
GenesisCare USA - Las Vegas
Las Vegas, Nevada 89109
Las Vegas, Nevada 89109
Sunrise Hospital and Medical Center
Las Vegas, Nevada 89109
Las Vegas, Nevada 89109
Urology Specialists of Nevada - Southwest
Las Vegas, Nevada 89113
Las Vegas, Nevada 89113
Radiation Oncology Centers of Nevada Southeast
Las Vegas, Nevada 89119
Las Vegas, Nevada 89119
Ann M Wierman MD LTD
Las Vegas, Nevada 89128
Las Vegas, Nevada 89128
Comprehensive Cancer Centers of Nevada - Northwest
Las Vegas, Nevada 89128
Las Vegas, Nevada 89128
GenesisCare USA - Vegas Tenaya
Las Vegas, Nevada 89128
Las Vegas, Nevada 89128
Las Vegas Urology - Cathedral Rock
Las Vegas, Nevada 89128
Las Vegas, Nevada 89128
Las Vegas Urology - Smoke Ranch
Las Vegas, Nevada 89128
Las Vegas, Nevada 89128
OptumCare Cancer Care at MountainView
Las Vegas, Nevada 89128
Las Vegas, Nevada 89128
Urology Specialists of Nevada - Northwest
Las Vegas, Nevada 89128
Las Vegas, Nevada 89128
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
Las Vegas, Nevada 89135
Las Vegas, Nevada 89135
Comprehensive Cancer Centers of Nevada - Town Center
Las Vegas, Nevada 89144
Las Vegas, Nevada 89144
Comprehensive Cancer Centers of Nevada-Summerlin
Las Vegas, Nevada 89144
Las Vegas, Nevada 89144
Summerlin Hospital Medical Center
Las Vegas, Nevada 89144
Las Vegas, Nevada 89144
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada 89148
Las Vegas, Nevada 89148
GenesisCare USA - Fort Apache
Las Vegas, Nevada 89148
Las Vegas, Nevada 89148
OptumCare Cancer Care at Fort Apache
Las Vegas, Nevada 89148
Las Vegas, Nevada 89148
Comprehensive Cancer Centers of Nevada - Central Valley
Las Vegas, Nevada 89169
Las Vegas, Nevada 89169
Hope Cancer Care of Nevada-Pahrump
Pahrump, Nevada 89048
Pahrump, Nevada 89048
Renown Regional Medical Center
Reno, Nevada 89502
Reno, Nevada 89502
Saint Mary's Regional Medical Center
Reno, Nevada 89503
Reno, Nevada 89503
Radiation Oncology Associates
Reno, Nevada 89509
Reno, Nevada 89509
Hackensack University Medical Center
Hackensack, New Jersey 07601
Hackensack, New Jersey 07601
Contact:
Site Public Contact
551-996-2897
Site Public Contact
551-996-2897
Newark Beth Israel Medical Center
Newark, New Jersey 07112
Newark, New Jersey 07112
Saint Joseph's Regional Medical Center
Paterson, New Jersey 07503
Paterson, New Jersey 07503
Presbyterian Hospital
Albuquerque, New Mexico 87106
Albuquerque, New Mexico 87106
University of New Mexico Cancer Center
Albuquerque, New Mexico 87106
Albuquerque, New Mexico 87106
Albany Medical Center
Albany, New York 12208
Albany, New York 12208
Contact:
Site Public Contact
518-262-5513
Site Public Contact
518-262-5513
Montefiore Medical Center-Einstein Campus
Bronx, New York 10461
Bronx, New York 10461
Montefiore Medical Center-Weiler Hospital
Bronx, New York 10461
Bronx, New York 10461
Children's Hospital at Montefiore
Bronx, New York 10467
Bronx, New York 10467
Montefiore Medical Center - Moses Campus
Bronx, New York 10467
Bronx, New York 10467
NYU Langone Hospital - Long Island
Mineola, New York 11501
Mineola, New York 11501
The Steven and Alexandra Cohen Children's Medical Center of New York
New Hyde Park, New York 11040
New Hyde Park, New York 11040
Contact:
Site Public Contact
718-470-3460
Site Public Contact
718-470-3460
NYP/Weill Cornell Medical Center
New York, New York 10065
New York, New York 10065
Contact:
Site Public Contact
212-746-1848
Site Public Contact
212-746-1848
Stony Brook University Medical Center
Stony Brook, New York 11794
Stony Brook, New York 11794
Contact:
Site Public Contact
800-862-2215
Site Public Contact
800-862-2215
New York Medical College
Valhalla, New York 10595
Valhalla, New York 10595
Contact:
Site Public Contact
914-594-3794
Site Public Contact
914-594-3794
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina 27599
Chapel Hill, North Carolina 27599
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina 28203
Charlotte, North Carolina 28203
Contact:
Site Public Contact
800-804-9376
Site Public Contact
800-804-9376
Wake Forest University Health Sciences
Winston-Salem, North Carolina 27157
Winston-Salem, North Carolina 27157
Contact:
Site Public Contact
336-713-6771
Site Public Contact
336-713-6771
Sanford Broadway Medical Center
Fargo, North Dakota 58122
Fargo, North Dakota 58122
Children's Hospital Medical Center of Akron
Akron, Ohio 44308
Akron, Ohio 44308
Contact:
Site Public Contact
330-543-3193
Site Public Contact
330-543-3193
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio 45229
Cincinnati, Ohio 45229
Rainbow Babies and Childrens Hospital
Cleveland, Ohio 44106
Cleveland, Ohio 44106
Contact:
Site Public Contact
216-844-5437
Site Public Contact
216-844-5437
Cleveland Clinic Foundation
Cleveland, Ohio 44195
Cleveland, Ohio 44195
Nationwide Children's Hospital
Columbus, Ohio 43205
Columbus, Ohio 43205
Dayton Children's Hospital
Dayton, Ohio 45404
Dayton, Ohio 45404
Contact:
Site Public Contact
800-228-4055
Site Public Contact
800-228-4055
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
Toledo, Ohio 43606
Toledo, Ohio 43606
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma 73104
Oklahoma City, Oklahoma 73104
Natalie Warren Bryant Cancer Center at Saint Francis
Tulsa, Oklahoma 74136
Tulsa, Oklahoma 74136
Contact:
Site Public Contact
918-494-2200
Site Public Contact
918-494-2200
Oregon Health and Science University
Portland, Oregon 97239
Portland, Oregon 97239
Geisinger Medical Center
Danville, Pennsylvania 17822
Danville, Pennsylvania 17822
Penn State Children's Hospital
Hershey, Pennsylvania 17033
Hershey, Pennsylvania 17033
Contact:
Site Public Contact
717-531-6012
Site Public Contact
717-531-6012
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania 19104
Philadelphia, Pennsylvania 19104
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania 15224
Pittsburgh, Pennsylvania 15224
Saint Francis Hospital
Greenville, South Carolina 29601
Greenville, South Carolina 29601
BI-LO Charities Children's Cancer Center
Greenville, South Carolina 29605
Greenville, South Carolina 29605
Contact:
Site Public Contact
864-241-6251
Site Public Contact
864-241-6251
Saint Francis Cancer Center
Greenville, South Carolina 29607
Greenville, South Carolina 29607
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota 57117-5134
Sioux Falls, South Dakota 57117-5134
East Tennessee Childrens Hospital
Knoxville, Tennessee 37916
Knoxville, Tennessee 37916
Contact:
Site Public Contact
865-541-8266
Site Public Contact
865-541-8266
The Children's Hospital at TriStar Centennial
Nashville, Tennessee 37203
Nashville, Tennessee 37203
Contact:
Site Public Contact
615-342-1919
Site Public Contact
615-342-1919
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee 37232
Nashville, Tennessee 37232
Contact:
Site Public Contact
800-811-8480
Site Public Contact
800-811-8480
Dell Children's Medical Center of Central Texas
Austin, Texas 78723
Austin, Texas 78723
Driscoll Children's Hospital
Corpus Christi, Texas 78411
Corpus Christi, Texas 78411
Medical City Dallas Hospital
Dallas, Texas 75230
Dallas, Texas 75230
Contact:
Site Public Contact
972-566-5588
Site Public Contact
972-566-5588
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas 75390
Dallas, Texas 75390
El Paso Children's Hospital
El Paso, Texas 79905
El Paso, Texas 79905
Cook Children's Medical Center
Fort Worth, Texas 76104
Fort Worth, Texas 76104
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas 77030
Houston, Texas 77030
M D Anderson Cancer Center
Houston, Texas 77030
Houston, Texas 77030
Covenant Children's Hospital
Lubbock, Texas 79410
Lubbock, Texas 79410
UMC Cancer Center / UMC Health System
Lubbock, Texas 79415
Lubbock, Texas 79415
Contact:
Site Public Contact
806-775-8590
Site Public Contact
806-775-8590
Children's Hospital of San Antonio
San Antonio, Texas 78207
San Antonio, Texas 78207
Methodist Children's Hospital of South Texas
San Antonio, Texas 78229
San Antonio, Texas 78229
University of Texas Health Science Center at San Antonio
San Antonio, Texas 78229
San Antonio, Texas 78229
University of Virginia Cancer Center
Charlottesville, Virginia 22908
Charlottesville, Virginia 22908
Inova Fairfax Hospital
Falls Church, Virginia 22042
Falls Church, Virginia 22042
Children's Hospital of The King's Daughters
Norfolk, Virginia 23507
Norfolk, Virginia 23507
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia 23298
Richmond, Virginia 23298
Carilion Children's
Roanoke, Virginia 24014
Roanoke, Virginia 24014
Valley Medical Center
Renton, Washington 98055
Renton, Washington 98055
Seattle Children's Hospital
Seattle, Washington 98105
Seattle, Washington 98105
Contact:
Site Public Contact
866-987-2000
Site Public Contact
866-987-2000
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington 99204
Spokane, Washington 99204
Mary Bridge Children's Hospital and Health Center
Tacoma, Washington 98405
Tacoma, Washington 98405
Madigan Army Medical Center
Tacoma, Washington 98431
Tacoma, Washington 98431
North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
Yakima, Washington 98902
Yakima, Washington 98902
Aurora Cancer Care-Southern Lakes VLCC
Burlington, Wisconsin 53105
Burlington, Wisconsin 53105
Aurora Saint Luke's South Shore
Cudahy, Wisconsin 53110
Cudahy, Wisconsin 53110
Aurora Health Care Germantown Health Center
Germantown, Wisconsin 53022
Germantown, Wisconsin 53022
Aurora Cancer Care-Grafton
Grafton, Wisconsin 53024
Grafton, Wisconsin 53024
Aurora BayCare Medical Center
Green Bay, Wisconsin 54311
Green Bay, Wisconsin 54311
Aurora Cancer Care-Kenosha South
Kenosha, Wisconsin 53142
Kenosha, Wisconsin 53142
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
Madison, Wisconsin 53718
Madison, Wisconsin 53718
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin 53792
Madison, Wisconsin 53792
Aurora Bay Area Medical Group-Marinette
Marinette, Wisconsin 54143
Marinette, Wisconsin 54143
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Milwaukee, Wisconsin 53209
Milwaukee, Wisconsin 53209
Aurora Saint Luke's Medical Center
Milwaukee, Wisconsin 53215
Milwaukee, Wisconsin 53215
Children's Hospital of Wisconsin
Milwaukee, Wisconsin 53226
Milwaukee, Wisconsin 53226
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Milwaukee, Wisconsin 53233
Milwaukee, Wisconsin 53233
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Oshkosh, Wisconsin 54904
Oshkosh, Wisconsin 54904
Aurora Cancer Care-Racine
Racine, Wisconsin 53406
Racine, Wisconsin 53406
Vince Lombardi Cancer Clinic-Sheboygan
Sheboygan, Wisconsin 53081
Sheboygan, Wisconsin 53081
Aurora Medical Center in Summit
Summit, Wisconsin 53066
Summit, Wisconsin 53066
Vince Lombardi Cancer Clinic-Two Rivers
Two Rivers, Wisconsin 54241
Two Rivers, Wisconsin 54241
Aurora Cancer Care-Milwaukee West
Wauwatosa, Wisconsin 53226
Wauwatosa, Wisconsin 53226
Aurora West Allis Medical Center
West Allis, Wisconsin 53227
West Allis, Wisconsin 53227
More Details
- NCT ID
- NCT05602194
- Status
- Recruiting
- Sponsor
- Children's Oncology Group
Detailed Description
PRIMARY OBJECTIVE: I. To determine in a randomized manner whether the addition of levocarnitine prophylaxis to asparaginase-containing regimens will decrease the incidence of conjugated hyperbilirubinemia (> 3 mg/dL) during ALL induction therapy for adolescents and young adults (adolescents and young adults [AYAs], age 15-39 years). SECONDARY OBJECTIVES: I. To examine the impact of levocarnitine prophylaxis on differences in the incidence of grade >= 3 alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevations during ALL Induction. II. To compare rates of minimal residual disease (MRD) positivity at end of Induction and describe MRD+ by end of consolidation (EOC) in those receiving ALL induction chemotherapy with and without levocarnitine. EXPLORATORY OBJECTIVES: I. To compare rates of toxicity and associated dose reductions for chemotherapy administered with and without concomitant levocarnitine supplementation. II. To compare across study arms the peak levels during Induction of conjugated and total bilirubin, AST, ALT, and duration of conjugated hyperbilirubinemia from onset > 3 mg/dL to =< 3 mg/dL. III. To describe the efficacy of levocarnitine prophylaxis to reduce the incidence and/or severity of early patient-reported chemotherapy-induced peripheral neuropathy. IV. To describe the three-year event-free and overall survival (EFS/OS) in those treated with and without levocarnitine prophylaxis. V. To examine the association of age with asparaginase activity and asparaginase-associated hepatotoxicity during induction. VI. To examine the association of body-mass-index (BMI) percentile (or absolute BMI for young adults) with asparaginase activity and asparaginase-associated hepatotoxicity during induction. VII. To describe adherence by self-report and pill-count to oral levocarnitine in patients randomized to the intervention arm. VIII. To examine the association of plasma levels of carnitine and related markers with the efficacy of levocarnitine supplementation. IX. To determine the impact of inherited genetic variation on hepatoxicity and levocarnitine efficacy. OUTLINE: Patients are randomized to 1 of 2 arms (arm A vs. B). ARM A: Patients receive levocarnitine orally (PO) or intravenously (IV) as a bolus over 2 to 3 minutes or by infusion (over 10 to 30 minutes or per institutional standard) starting prior to standard of care induction chemotherapy with pegaspargase or calaspargase pegol and continued through the earlier of the last day of Induction phase (i.e., day prior to start of next phase) or Induction day 35. Patients may also undergo blood sample collection during screening and on study. ARM B: Patients receive standard of care induction chemotherapy with pegaspargase or calaspargase pegol on study. Patients may also undergo blood sample collection during screening and on study. ARM C (RESCUE): Patients in Arms A and B who develop conjugated hyperbilirubinemia > 3 mg/dL during induction may receive levocarnitine rescue PO or IV as a bolus dose over 2 to 3 minutes or by infusion (over 10 to 30 minutes or per institutional standard) until resolution of conjugated hyperbilirubinemia =< 3 mg/dL (or start of consolidation or the next treatment phase, whichever occurs first).