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Studying the Effect of Levocarnitine in Protecting the Liver From Chemotherapy for Leukemia or Lymphoma

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ClinicalTrials.gov Identifier: NCT05602194
Recruitment Status : Recruiting
First Posted : November 2, 2022
Last Update Posted : May 16, 2024
Sponsor:
Information provided by (Responsible Party):
Children's Oncology Group

Tracking Information
First Submitted Date  ICMJE October 18, 2022
First Posted Date  ICMJE November 2, 2022
Last Update Posted Date May 16, 2024
Actual Study Start Date  ICMJE August 24, 2023
Estimated Primary Completion Date December 31, 2027   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 25, 2023)
Incidence of conjugated hyperbilirubinemia >3 mg/dL during induction therapy [ Time Frame: During induction therapy (up-to 35-days after initiating induction chemotherapy) ]
For patients assigned to arms A and B, the investigators will separately estimate the proportion of patients who experience conjugated hyperbilirubinemia > 3mg/dL during induction chemotherapy by arm along with corresponding 95% confidence intervals.
Original Primary Outcome Measures  ICMJE
 (submitted: October 28, 2022)
Incidence of conjugated hyperbilirubinemia >3 mg/dL during induction therapy [ Time Frame: During induction therapy (up-to ~35-days after treatment starting induction chemotherapy) ]
For patients assigned to arms A and B, the proportion having conjugated hyperbilirubinemia > 3mg/dL during induction chemotherapy will be estimated along with 95% confidence intervals.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 25, 2023)
  • Incidence of grade >= 3 alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevations during induction therapy [ Time Frame: During induction therapy (up-to 35-days after initiating induction chemotherapy) ]
    For patients assigned to arms A and B, the investigators will separately estimate the proportion of patients who experience grade >= 3 alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevations during induction chemotherapy by arm along with corresponding 95% confidence intervals.
  • Incidence of minimal residual disease (MRD) positivity (MRD >= 0.01%) [ Time Frame: At end of induction chemotherapy (up-to 35-days after initiating induction chemotherapy), and at end of consolidation chemotherapy (up-to day 56 days after initiating induction chemotherapy) ]
    For patients assigned to arms A and B, the proportion having MRD positivity at the end of induction chemotherapy will be estimated separately by arm along with corresponding 95% confidence intervals. For patients assigned to arms A and B, the proportion having MRD positivity at the end of consolidation chemotherapy will be estimated separately by arm along with corresponding 95% confidence intervals (only patients with end of consolidation MRD evaluated and who did not get placed on the rescue arm C will be included).
Original Secondary Outcome Measures  ICMJE
 (submitted: October 28, 2022)
  • Incidence of grade >= 3 alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevations during induction therapy [ Time Frame: Up to 35 days (induction phase) ]
    For patients assigned to arms A and B, the proportion having >= 3 ALT or AST elevations during induction chemotherapy will be estimated along with 95% confidence intervals.
  • Minimal residual disease (MRD) positivity [ Time Frame: At end of induction chemotherapy and at end of consolidation chemotherapy (up-to day ~56 after initiation induction chemotherapy) ]
    For patients assigned to arms A and B, the proportion having MRD positivity at the end of induction chemotherapy will be estimated along with 95% confidence intervals. For patients assigned to arms A and B, the proportion having MRD positivity at the end of consolidation chemotherapy will be estimated along with 95% confidence intervals.
Current Other Pre-specified Outcome Measures
 (submitted: August 31, 2023)
  • Incidence of CTCAE grade >= 4 adverse events during induction chemotherapy [ Time Frame: Up to 35 days (induction phase) ]
    For patients assigned to arms A and B, the proportion experiencing CTCAE grade >=4 adverse events by the end of induction chemotherapy will be estimated along with 95% confidence intervals.
  • Incidence of daunorubicin, vincristine, and/or asparaginase chemotherapy dose reductions during induction chemotherapy [ Time Frame: Up to 35 days (induction phase) ]
    For patients assigned to arms A and B, the proportion receiving a dose reduction during induction chemotherapy relative to planned doses at the beginning of induction chemotherapy for daunorubicin, vincristine, and/or asparaginase will be estimated along with 95% confidence intervals
  • Percentage of planned dose given for daunorubicin, vincristine, and/or asparaginase during induction chemotherapy [ Time Frame: Up to 35 days (induction phase) ]
    For patients assigned to arms A and b, the median percent planned dose given during induction will also be calculated as well as 95% confidence intervals.
  • Peak levels during induction of conjugated bilirubin [ Time Frame: Up to 35 days (induction phase) ]
    For patients assigned to arms A and B, the investigators will calculate median peak conjugated bilirubin as well as corresponding 95% confidence intervals.
  • Peak levels during induction of total bilirubin [ Time Frame: Up to 35 days (induction phase) ]
    For patients assigned to arms A and B, the investigators will calculate median peak ALT as well as corresponding 95% confidence intervals.
  • Peak levels of AST during induction chemotherapy [ Time Frame: Up to 35 days (induction phase) ]
    For patients assigned to arms A and B, the investigators will calculate median peak ALT as well as corresponding 95% confidence intervals.
  • Peak levels of ALT during induction chemotherapy [ Time Frame: Up to 35 days (induction phase) ]
    For patients assigned to arms A and B, the investigators will calculate median peak ALT as well as corresponding 95% confidence intervals.
  • Days of conjugated hyperbilirubinemia (> 3 mg/dL) to <=3 mg/dL during induction [ Time Frame: Up to 35 days (induction phase) ]
    For patients assigned to arms A, B, and C, the investigators will calculate the median days from onset of conjugated hyperbilirubinemia as well as 95% confidence intervals.
  • Severity of patient-reported chemotherapy induced peripheral neuropathy (CIPN) as measured by the 11-question Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-NTX) survey [ Time Frame: Up to 35 days (induction phase) ]
    The 11-question FACT/GOG-NTX survey will be used to assess patient reported CIPN, where a higher score indicates more severe CIPN. For patients on arms A and B, a median and corresponding 95% confidence interval will be estimated and reported.
  • Event free survival (EFS) [ Time Frame: The time from randomization to first event (relapse, second malignant neoplasm, remission or death) or date of last contact for those who are disease-free, assessed up to 3 years ]
    For EFS analysis, 3-year EFS probabilities and corresponding 95% CI will be estimated for Arms A and B, separately, using the Kaplan Meier method. A log-rank test will be used to compare EFS between Arm A versus Arm B (Arm C patients will not contribute to this analysis after they start levocarnitine rescue). Additional EFS analyses comparing Arms A versus B will also be performed using Cox regression models adjusted for "levocarnitine rescue" (i.e., Arm C patients/time) as a time-varying covariate. Hazard ratio and the corresponding 95%CI will be reported for each arm.
  • Overall survival (OS) [ Time Frame: Time from study entry to death or date of last contact for those alive at last contact, assessed up to 3 years ]
    For OS analysis, 3-year OS probabilities and corresponding 95% CI will be estimated for Arms A and B, separately, using the Kaplan Meier method.
  • Asparaginase activity [ Time Frame: Days 8, 15, and 22 ]
    Spearman's correlation coefficients and corresponding 95% confidence intervals will be reported comparing asparaginase activity to age and BMI.
  • Association of body-mass-index (BMI) percentile (or absolute BMI for young adults) with asparaginase activity and asparaginase-associated hepatotoxicity during induction therapy [ Time Frame: Days 8, 15, and 22 ]
    The association of BMI percentile with asparaginase activity will be assessed using Spearman's correlation. Logistic regression will be used to separately assess the relationship of BMI (considered as a continuous variable and an ordinal variable) and asparaginase activity with hepatotoxicity (conjugated hyperbilirubinemia, ALT) dichotomized as conjugated hyperbilirubinemia >3 versus =< 3 mg/dl and CTCAE grade >= 3 versus < 3 AST or ALT, respectively. Analyses will be performed separately for asparaginase activity measured on Days ~8, 15, and 22 and for Arms A and B.
  • Adherence to oral levocarnitine during induction chemotherapy measured by percentage of pills returned relative to those prescribed [ Time Frame: Up to 35 days (induction phase) ]
    Descriptive statistics (mean (sd) or median (range) as appropriate) will be used to summarize adherence to levocarnitine tablets during induction in AYA patients randomized to the intervention Arm A as assessed by self-report (% doses compliant) and pill-counts (% pills returned). The percentage of doses compliant will be calculated as: the number of reported missed doses / total prescribed doses for the entire induction period. And the percentage of pills returned will be calculated as the number of pills returned / (number of pills dispensed - number of pills prescribed not taken [i.e., for prescribed dose reductions for toxicity for the entire induction period]).
  • Adherence to oral levocarnitine measured by percentage dose compliance (% doses reported taken relative to prescribed) [ Time Frame: Up to 35 days (induction phase) ]
    The investigators will report the median percentage dose compliance across patients assigned to arm A as well as a 95% confidence interval.
  • Mean plasma levels of carnitine [ Time Frame: Up to 3 years ]
    The Investigators will calculate mean plasma levels of carnitine at baseline and at steady state for patients in arms A and B who do and do not experience conjugated hyperbilirubinemia >3 mg/dL and will calculate corresponding 95% confidence intervals.
  • Impact inherited genetic variation on hepatoxicity and levocarnitine efficacy [ Time Frame: Up to 3 years ]
    This aim will use specimens banked for future research to describe the association of candidate genes (PNPLA3, SOD2, GST family, other) with conjugated hyperbilirubinemia >3 mg/dL and CTCAE Grade ≥3 AST or ALT elevations between treatment arms. Analyses will include ethnic and racial differences, with ancestry determined by self-report and complementary admixture mapping. The association of observed genetic differences with oxidant stress markers (e.g., protein oxidation, lipid peroxidation, total oxidant capacity) pre- and post-asparaginase will be assessed. In general, a multivariable logistic regression model will be used to examine the association between the occurrence of the primary endpoint and the genetic variant of interest, inclusive of covariates: age, obesity, and treatment versus control arm (1:1).
Original Other Pre-specified Outcome Measures
 (submitted: October 28, 2022)
  • Incidence of CTCAE grade >= 4 adverse events during induction chemotherapy [ Time Frame: Up to 35 days (induction phase) ]
    For patients assigned to arms A and B, the proportion experiencing CTCAE grade >=4 adverse events by the end of induction chemotherapy will be estimated along with 95% confidence intervals.
  • Incidence of daunorubicin, vincristine, and/or asparaginase chemotherapy dose reductions during induction chemotherapy [ Time Frame: Up to 35 days (induction phase) ]
    For patients assigned to arms A and B, the proportion receiving a dose reduction during induction chemotherapy relative to planned doses at the beginning of induction chemotherapy for daunorubicin, vincristine, and/or asparaginase will be estimated along with 95% confidence intervals.
  • Percentage of planned dose given for daunorubicin, vincristine, and/or asparaginase during induction chemotherapy [ Time Frame: Up to 35 days (induction phase) ]
    For patients assigned to arms A and b, the median percent planned dose given during induction will also be calculated as well as 95% confidence intervals.
  • Peak levels during induction of conjugated bilirubin [ Time Frame: Up to 35 days (induction phase) ]
    For patients assigned to arms A and B, the investigators will calculate median peak conjugated bilirubin as well as corresponding 95% confidence intervals.
  • Peak levels of total bilirubin during induction chemotherapy [ Time Frame: Up to 35 days (induction phase) ]
    For patients assigned to arms A and B, the investigators will calculate median peak total bilirubin as well as corresponding 95% confidence intervals.
  • Peak levels of AST during induction chemotherapy [ Time Frame: Up to 35 days (induction phase) ]
    For patients assigned to arms A and B, the investigators will calculate median peak AST as well as corresponding 95% confidence intervals.
  • Peak levels of ALT during induction chemotherapy [ Time Frame: Up to 35 days (induction phase) ]
    For patients assigned to arms A and B, the investigators will calculate median peak ALT as well as corresponding 95% confidence intervals.
  • Days of conjugated hyperbilirubinemia (>3 mg/dL) to <=3 mg/dL during induction [ Time Frame: Up to 35 days (induction phase) ]
    For patients assigned to arms A, B, and C, the investigators will calculate the median days from onset of conjugated hyperbilirubinemia as well as 95% confidence intervals.
  • Severity of patient-reported chemotherapy induced peripheral neuropathy (CIPN) as measured by the 11-question Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-NTX) survey [ Time Frame: Up to 35 days (induction phase) ]
    The 11-question FACT/GOG-NTX survey will be used to assess patient reported CIPN, where a higher score indicates more severe CIPN. For patients on arms A and B, a median and corresponding 95% confidence interval will be estimated and reported.
  • Event free survival (EFS) [ Time Frame: The time from randomization to first event (relapse, second malignant neoplasm, remission or death) or date of last contact for those who are disease-free, assessed up to 3 years ]
    For EFS analysis, 3-year EFS probabilities and corresponding 95% CI will be estimated for Arms A and B, separately, using the Kaplan Meier method.
  • Overall survival (OS) [ Time Frame: Time from study entry to death or date of last contact for those alive at last contact, assessed up to 3 years ]
    For OS analysis, 3-year OS probabilities and corresponding 95% CI will be estimated for Arms A and B, separately, using the Kaplan Meier method.
  • Asparaginase activity [ Time Frame: Days 8, 15, and 22 ]
    Spearman's correlation coefficients and corresponding 95% confidence intervals will be reported comparing asparaginase activity to age and BMI.
  • Adherence to oral levocarnitine during induction chemotherapy measured by percentage of pills returned relative to those prescribed [ Time Frame: Up to 35 days (induction phase) ]
    The investigators will report the median percentage of tables returned at the end of induction chemotherapy across patients assigned to arm A as well as a 95% confidence interval.
  • Adherence to oral levocarnitine measured by percentage dose compliance (% doses reported taken relative to prescribed) [ Time Frame: Up to 35 days (induction phase) ]
    The investigators will report the median percentage dose compliance across patients assigned to arm A as well as a 95% confidence interval.
  • Mean plasma levels of carnitine [ Time Frame: up to 35 days (induction phase) ]
    The investigators will calculate mean plasma levels of carnitine at baseline and at steady state for patients in arms A and B who do and do not experience conjugated hyperbilirubinemia >3 mg/dL and will calculate corresponding 95% confidence intervals.
 
Descriptive Information
Brief Title  ICMJE Studying the Effect of Levocarnitine in Protecting the Liver From Chemotherapy for Leukemia or Lymphoma
Official Title  ICMJE A Randomized Trial of Levocarnitine Prophylaxis to Prevent Asparaginase-Associated Hepatotoxicity in Adolescents and Young Adults Receiving Acute Lymphoblastic Leukemia Therapy
Brief Summary This phase III trial compares the effect of adding levocarnitine to standard chemotherapy 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.
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) prior to 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 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 supplementation until resolution of conjugated hyperbilirubinemia =< 3 mg/dL (or start of consolidation or the next treatment phase, whichever occurs first).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Condition  ICMJE
  • 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
Intervention  ICMJE
  • Procedure: Biospecimen Collection
    Undergo blood sample collection
    Other Names:
    • Biological Sample Collection
    • Biospecimen Collected
    • Specimen Collection
  • Drug: Calaspargase Pegol
    Given standard of care calaspargase pegol
    Other Names:
    • Asparaginase (Escherichia coli Isoenzyme II), Conjugate with alpha-(((2,5-Dioxo-1-pyrrolidinyl)oxy)carbonyl)-omega-methoxypoly(oxy-1,2-ethanediyl)
    • Asparlas
    • Calaspargase Pegol-mknl
    • EZN-2285
    • SC-PEG E. Coli L-Asparaginase
    • Succinimidyl Carbonate Monomethoxypolyethylene Glycol E. coli L-Asparaginase
  • Dietary Supplement: Levocarnitine
    Given PO or IV
    Other Names:
    • Carnitor
    • L-carnitine
  • Drug: Pegaspargase
    Given standard of care pegaspargase
    Other Names:
    • L-Asparaginase with Polyethylene Glycol
    • Oncaspar
    • Oncaspar-IV
    • PEG-Asparaginase
    • PEG-L-Asparaginase
    • PEG-L-Asparaginase (Enzon - Kyowa Hakko)
    • PEGLA
    • Polyethylene Glycol L-Asparaginase
    • Polyethylene Glycol-L-Asparaginase
  • Other: Quality-of-Life Assessment
    Ancillary studies
    Other Name: Quality of Life Assessment
Study Arms  ICMJE
  • Experimental: Arm A (levocarnitine, standard of care chemotherapy)
    Patients receive levocarnitine PO or IV prior to standard of care induction chemotherapy with pegaspargase or calaspargase pegol on study. Patients may also undergo blood sample collection during screening and on study.
    Interventions:
    • Procedure: Biospecimen Collection
    • Drug: Calaspargase Pegol
    • Dietary Supplement: Levocarnitine
    • Drug: Pegaspargase
    • Other: Quality-of-Life Assessment
  • 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.
    Interventions:
    • Procedure: Biospecimen Collection
    • Drug: Calaspargase Pegol
    • Drug: Pegaspargase
    • Other: Quality-of-Life Assessment
  • 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 supplementation until resolution of conjugated hyperbilirubinemia =< 3 mg/dL (or start of consolidation or the next treatment phase, whichever occurs first).
    Intervention: Dietary Supplement: Levocarnitine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 28, 2022)
440
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2027
Estimated Primary Completion Date December 31, 2027   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
  • 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)
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 15 Years to 40 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05602194
Other Study ID Numbers  ICMJE ACCL1931
NCI-2022-08058 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
ACCL1931 ( Other Identifier: Children's Oncology Group )
COG-ACCL1931 ( Other Identifier: DCP )
ACCL1931 ( Other Identifier: CTEP )
U24CA196173 ( U.S. NIH Grant/Contract )
UG1CA189955 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Children's Oncology Group
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Children's Oncology Group
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Etan Orgel Children's Oncology Group
PRS Account Children's Oncology Group
Verification Date May 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP