Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Rare Diseases

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Childhood Acute Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Lymphosarcoma

Lipid Regulating Agents

All Drugs and Chemicals

Atorvastatin

Hydroxymethylglutaryl-CoA Reductase Inhibitors

Anticholesteremic Agents

Hypolipidemic Agents

Antimetabolites

Enzyme Inhibitors

6-Months Atorvastatin Therapy; 40mg oral, once daily

6-Months Placebo (sugar pill); oral, once daily

6-Months of Atorvastatin (Lipitor); 40mg, oral, once daily.

6-Months of placebo (sugar) pill; oral, once daily

Sugar Pill (Placebo)

Aaron S Kelly, Ph.D.

Adult survivors of childhood cancer are at high risk of developing cardiovascular disease. Therapies used to treat many cancers, such as chemotherapy and radiation, likely cause damage to the surface of the artery wall called the endothelial layer, leading to the induction of atherosclerosis and eventual cardiovascular disease. HMG coenzyme A reductase inhibitors, or statins, improve endothelial function independent of cholesterol-lowering. In addition, statins have been shown to reduce arterial stiffness and slow arterial thickening. Despite strong evidence supporting the vascular benefits of statins in many different patient populations, these medications have never been studied in cancer survivors. Therefore, the overall objective of this study is to evaluate the effects of statin therapy on vascular health in young adult survivors of childhood cancer.

Twenty-four young adult (age 18-39 years old) survivors of childhood acute lymphoblastic leukemia (ALL) or non-Hodgkin's lymphoma (NHL) will be enrolled in a six-month randomized, double-blind (participants and investigators), placebo-controlled pilot clinical trial comparing the effects of atorvastatin versus placebo on endothelial function and other measures of vascular health.

Our primary objective is to evaluate the effects of 6-months of statin therapy on conduit artery endothelial function in young adult survivors of childhood cancer. The investigators hypothesize that, compared to placebo, atorvastatin will significantly increase brachial artery flow-mediated dilation in survivors of childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma.

Adult survivors of childhood cancer are at seven times the risk of dying from cardiovascular disease compared to the general population. The increased risk is thought to be the result of the therapies used to treat the cancer such as chemotherapy and radiation. These therapies likely cause damage to the endothelial cells, which line the arterial wall and, when function properly, offer protection from atherosclerosis. Young adult survivors of childhood ALL have reduced endothelial function, or endothelial dysfunction, compared to healthy controls. Endothelial dysfunction is considered an early manifestation of atherosclerosis and therefore is an ideal target of therapy in order to reduce the risk of cardiovascular disease. Interventions that improve endothelial function in young adult survivors of childhood cancer may be beneficial in terms of mitigating the medium- and long-term risk of developing this chronic disease.

HMG coenzyme A reductase inhibitors, or statins, are widely used for cardiovascular disease risk reduction. These medications are primarily used to reduce levels of total- and low-density lipoprotein (LDL) -cholesterol. Meta-analyses have consistently demonstrated that statin therapy improves endothelial function in a wide array of patient populations. Beyond their well-described vascular benefits, statins are an attractive therapeutic option for cardiovascular disease risk reduction due to their strong safety profile.

Despite the clear potential for endothelial function improvement and cardiovascular risk reduction, statin therapy has never been evaluated in survivors of childhood cancer. Although statins have been well-studied in other patient populations at risk for cardiovascular disease, there is strong justification for evaluation in cancer survivors since the mechanisms responsible for the vascular problems in these individuals (treatment-induced vascular toxicity) differ from traditional atherosclerosis. Therefore, the objective of the current study is to assess the ability of statin therapy to improve endothelial function, arterial stiffness, and arterial thickening in young adult survivors of childhood cancer. The focus of the study will be on survivors of hematologic malignancies, acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL), since the former has been shown to be associated with endothelial impairments and both cancers share common treatment exposures (chemotherapy and radiation), which is likely the primary factor responsible for endothelial dysfunction in these individuals.

Twenty-four young adult (age 18-39 years old) survivors of childhood acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL)will be enrolled in a six-month randomized, double-blind (participants and investigators), placebo-controlled pilot clinical trial comparing the effects of atorvastatin versus placebo on endothelial function and other measures of vascular health. Following baseline testing, subjects will be randomly assigned (1:1) to either atorvastatin or placebo. Participants will return at 1-month and 3-months for assessment of safety (blood draw and adverse event assessment) and medication compliance and at 6-months for assessment of safety, medication compliance, and reassessment of baseline variables.

Statin Therapy in Young Adult Survivors of Childhood Cancer

Pilot Study of Statin Therapy in Young Adult Survivors of Childhood Cancer

At this time we have no plan to share the IPD.

Carotid Artery Compliance is a measure of arterial stiffness. Higher arterial stiffness places persons at higher risk for CVD.

University of Minnesota

6-Months Atorvastatin Therapy; 40mg oral, once daily

Atorvastatin: 6-Months of Atorvastatin (Lipitor); 40mg, oral, once daily.

6-Months Placebo (sugar pill); oral, once daily

Sugar Pill (Placebo): 6-Months of placebo (sugar) pill; oral, once daily

Total

Age, Categorical

Age, Continuous

Gender

United States

Region of Enrollment

Cameron Naughton

Physician withdrawals, loss to follow-up, drug compliance \<70%, unrelated injury, and self-withdrawal reduced number analyzed. Also, participant movement during FMD assessment and/or poor ultrasound image quality due to difficult brachial artery anatomy or poor circulation led to some unusable data and thus lowered the analyzable sample size.

Change From Baseline in Brachial Artery Flow-Mediated Dilation at 6-months

Discrepant sample sizes are due to lack of reliability of measures. If measures were unreliable they were excluded.

Change From Baseline in Carotid Artery Compliance at 6-Months

Change From Baseline in Carotid Artery Distensibility at 6-Months

Change From Baseline in Pulse Wave Velocity at 6-Months

Change From Baseline in Augmentation Index at 6-Months

Change From Baseline in Carotid Intima-Media Thickness at 6-Months

Overall Study

Symptoms and General Pathology

Digestive System Diseases

Necrosis

Crohn Disease

Inflammatory Bowel Diseases

Intestinal Diseases

Gastroenteritis

Gastrointestinal Diseases

Pediatric Crohn's Disease

Antiemetics

Dermatologic Agents

Gastrointestinal Agents

Antineoplastic Agents

Antirheumatic Agents

Reproductive Control Agents

Micronutrients

Hematinics

Central Nervous System Depressants

Vitamins

Other Dietary Supplements

Ondansetron

Methotrexate

Folic Acid

Vitamin B Complex

Benzocaine

Folic Acid Antagonists

Immunosuppressive Agents

Immunologic Factors

Folinic Acid

Folate

Vitamin B9

Tannic Acid

Methotrexate (10, 12.5, or 15 mg), once weekly. Weight-based dosing. Ondansetron (4 mg), twice weekly, 1 hour prior to methotrexate dose and the morning after methotrexate dose.

Folic Acid (1 mg) daily

Placebo for methotrexate, once weekly. Placebo for ondansetron, twice weekly, 1 hour prior to methotrexate placebo dose and the morning after methotrexate placebo dose.

Folic Acid (1 mg) daily

1. Oral methotrexate (MTX): The weekly dose will be 15 mg for children ≥ 40kg, 12.5 mg for children 30 to \<40 kg, and 10 mg for children 20 to \<30 kg.
2. A twice per week, 4mg dose of ondansetron will be provided as pre-treatment to prevent nausea (study provider may opt-out of this component based on clinical judgement).
3. A 1 mg dose of folic acid per day will be provided. This will help to reduce the risk of side effects in the MTX group.

Drug kits will contain a 3 month supply of each medication. Refills will be provided every 3 months until week 156 unless there is a failure to induce and maintain remission, development of unacceptable toxicity, pregnancy in a female participant, or failure of the participant to attend scheduled study visits.

1. Placebo for methotrexate: The weekly dose will mimic that of methotrexate.
2. Placebo for ondansetron: The weekly dose will mimic that of ondansetron (study provider may opt-out of this component based on clinical judgement).
3. A 1 mg dose of folic acid per day will be provided to maintain blinding.

Drug kits will contain a 3 month supply of each medication. Refills will be provided every 3 months until week 156 unless there is a failure to induce and maintain remission, development of unacceptable toxicity, pregnancy in a female participant, or failure of the participant to attend scheduled study visits.

Sugar pill (placebo)

Michael D Kappelman, MD

The purpose of this study is to determine whether adding low dose methotrexate to anti -TNF therapy is more effective than treatment with anti-TNF therapy alone in inducing and maintaining steroid-free remission for children with Crohn's Disease.

Overall study duration: 6 years Multi-center study: up to 42 centers

Number of subjects: 425 Duration of treatment for each subject: up to 156 weeks (3 years)

The primary endpoint is percent of patients who experienced treatment failure over time.

Low Dose Oral Methotrexate in Pediatric Crohn's Disease Patients Initiating Anti-Tumor Necrosis Factor (Anti-TNF) Therapy

A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Pragmatic Clinical Trial To Evaluate The Effectiveness Of Low Dose Oral Methotrexate In Patients With Pediatric Crohn's Disease Initiating Anti-TNF Therapy

Treatment failure is defined as follows:

1. Failure to achieve remission (short pediatric Crohn's disease activity index \[SPCDAI\] \< 15) by the week 26 visit;
2. If study initiated on steroids, failure to complete steroid taper by week 16;
3. Short pediatric Crohn's disease activity index (SPCDAI) ≥ 15 attributed to active Crohn's disease, at two or more consecutive visits beyond the week 26 visit. Elevated SPCDAI (≥ 15) due to a non-Inflammatory Bowel Disease (IBD) reason does not count toward this outcome;
4. Hospitalization for active Inflammatory Bowel Disease or abdominal surgery after week 25;
5. Use of oral prednisone or prednisolone, enteral release budesonide, or intravenous (IV) methylprednisolone for over 10 weeks cumulatively, beyond week 16;
6. Discontinuation of anti-TNF agent and/or study drug for lack of effectiveness or toxicity.

T-scores are a continuous variable. The mean in the general population is 50 (SD=10). Scores above 50 represent higher than average pain interference and scores below 50 represent lower than average pain interference. Minimal important differences (MIDs) for many PROMIS domains are in the range of 2 to 6.

The investigators will compare the mean of PROMIS Pain Interference T-scores at week 52 between the treatment groups.

T-scores are a continuous variable. The mean in the general population is 50 (SD=10). Scores above 50 represent higher than average pain interference and scores below 50 represent lower than average pain interference. Minimal important differences (MIDs) for many PROMIS domains are in the range of 2 to 6.

The investigators will compare the mean of PROMIS Pain Interference T-scores at week 104 between the treatment groups

T-scores are a continuous variable. The mean in the general population is 50 (SD=10). Scores above 50 represent higher than average fatigue and scores below 50 represent lower than average fatigue. Minimal important differences (MIDs) for many PROMIS domains are in the range of 2 to 6.

The investigators will compare the mean of PROMIS Fatigue T-scores at week 52 between the treatment groups

T-scores are a continuous variable. The mean in the general population is 50 (SD=10). Scores above 50 represent higher than average fatigue and scores below 50 represent lower than average fatigue. Minimal important differences (MIDs) for many PROMIS domains are in the range of 2 to 6.

The investigators will compare the mean of PROMIS Fatigue T-scores at week 104 between the treatment groups

Percent of patients with positive anti-TNF antibody will be compared between the two treatment groups using the chi-squared test.

Patient-Centered Outcomes Research Institute

ImproveCareNow (ICN)

The Leona M. and Harry B. Helmsley Charitable Trust

Children's Hospital Medical Center, Cincinnati

Grifols Diagnostics Solutions, Inc

National Institutes of Health (NIH)

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

University of North Carolina, Chapel Hill

Methotrexate (10, 12.5, or 15 mg), once weekly. Weight-based dosing. Ondansetron (4 mg), twice weekly, 1 hour prior to methotrexate dose and the morning after methotrexate dose.

Folic Acid (1 mg) daily

Methotrexate: 1) Oral methotrexate (MTX): The weekly dose will be 15 mg for children ≥ 40kg, 12.5 mg for children 30 to \<40 kg, and 10 mg for children 20 to \<30 kg. 2) A twice per week, 4mg dose of ondansetron will be provided as pre-treatment to prevent nausea (study provider may opt-out of this component based on clinical judgement). 3) A 1 mg dose of folic acid per day will be provided. This will help to reduce the risk of side effects in the MTX group.

Drug kits will contain a 3 month supply of each medication. Refills will be provided every 3 months until week 156 unless there is a failure to induce and maintain remission, development of unacceptable toxicity, pregnancy in a female participant, or failure of the participant to attend scheduled study visits.

Placebo for methotrexate, once weekly. Placebo for ondansetron, twice weekly, 1 hour prior to methotrexate placebo dose and the morning after methotrexate placebo dose.

Folic Acid (1 mg) daily

Sugar pill (placebo): 1) Placebo for methotrexate: The weekly dose will mimic that of methotrexate. 2) Placebo for ondansetron: The weekly dose will mimic that of ondansetron (study provider may opt-out of this component based on clinical judgement). 3) A 1 mg dose of folic acid per day will be provided to maintain blinding.

Drug kits will contain a 3 month supply of each medication. Refills will be provided every 3 months until week 156 unless there is a failure to induce and maintain remission, development of unacceptable toxicity, pregnancy in a female participant, or failure of the participant to attend scheduled study visits.

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Infliximab

Adalimumab

Tumor Necrosis Factor (TNF) Inhibitor at Baseline

Modified Intent to Treat population presented.

Michael Kappelman, MD, MPH

Percent of Participants Experiencing Treatment Failure

Population includes those who completed surveys.

Mean Patient Reported Outcome Measurement and Information System (PROMIS ) Pain Interference T-score-52 Weeks

Mean Patient Reported Outcome Measurement and Information System (PROMIS ) Pain Interference T-score-week 104

Mean PROMIS (Patient Reported Outcome Measurement and Information System) Fatigue T Score-week 52

Mean PROMIS (Patient Reported Outcome Measurement and Information System) Fatigue T Score-week 104

Analysis includes participants who provided a blood sample.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Statin Therapy in Young Adult Survivors of Childhood Cancer	NCT01733953	Cardiovascular ... Childhood ALL Childhood NHL	Atorvastatin Sugar Pill (Pla...	18 Years - 39 Years	University of Minnesota
Low Dose Oral Methotrexate in Pediatric Crohn's Disease Patients Initiating Anti-Tumor Necrosis Factor (Anti-TNF) Therapy	NCT02772965	Pediatric Crohn...	Methotrexate Sugar pill (pla...	- 20 Years	University of North Carolina, Chapel Hill

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