Eltrombopag vs Standard Front Line Management for Newly Diagnosed Immune Thrombocytopenia (ITP) in Children

A Phase III Study of Eltrombopag vs Standard Front Line Management for Newly Diagnosed Immune Thrombocytopenia in Children

Sponsors

Lead Sponsor: Baylor College of Medicine

Collaborator: Boston Children's Hospital
University of California, San Francisco

Source Baylor College of Medicine
Brief Summary

This is an investigator initiated, multicenter, open label, randomized phase 3 study for subjects with newly diagnosed ITP from ages 1 to less than 18 years old.

Detailed Description

This is a prospective, open label, randomized, two-arm, multi-center Phase 3 trial.

Patients with newly diagnosed ITP are randomized 2:1 to receive the experimental treatment, eltrombopag, or investigator's choice of 3 standard therapies. The primary objective is to determine if the proportion of patients with platelet response is significantly greater in patients treated with eltrombopag compared to those treated with standard therapies.

Overall Status Recruiting
Start Date May 2, 2019
Completion Date November 30, 2024
Primary Completion Date May 1, 2022
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Proportion of patients with a platelet response 12 weeks
Secondary Outcome
Measure Time Frame
Bleeding Score 1 year
Number of rescue therapies 12 weeks
Platelet response 12 weeks
Need for treatment 6 months
Treatment response 1 year
Number of 2nd line therapies 52 weeks
Regulatory T-Cells 1 year
KIT Scores 1 year
Hockenberry Fatigue Scale-Parent 1 year
Blood Iron values 1 year
Safety evaluations 1 year
Enrollment 162
Condition
Intervention

Intervention Type: Drug

Intervention Name: Eltrombopag

Description: Starting dose for eltrombopag will be based on manufacturer recommendations, and drug will be titrated to effect per guidelines. Children 1 to 5 years: Initial: 25 mg once daily Children ≥6 years and Adolescents: Initial: 50 mg once daily (25 mg once daily for patients of East-Asian ethnicity [e.g., Chinese, Japanese, Korean, Taiwanese]) Dose should be titrated based on platelet response. Maximum dose: 75 mg once daily.

Arm Group Label: Eltrombopag

Intervention Type: Drug

Intervention Name: Steroids

Description: Prednisone/Prednisolone 4mg/kg/day (Max 120 mg/day) x 4 day

Arm Group Label: Standard first-line therapy

Intervention Type: Drug

Intervention Name: IVIG

Description: IVIG 1 g/kg x1 (no steroids for pre-medication or adjunctive therapy)

Arm Group Label: Standard first-line therapy

Intervention Type: Drug

Intervention Name: Rho(D) Immune Globulin

Description: Anti-D globulin 75 mcg/kg x1 (no steroids for pre-medication or adjunctive therapy)

Arm Group Label: Standard first-line therapy

Eligibility

Criteria:

Inclusion Criteria:

- Age: 1- <18 years

- Newly diagnosed ITP (<3 months from diagnosis (first abnormal platelet count), per international working group definition17)

- Platelets <30 x 10^9/L at screening

- Requires pharmacologic treatment from the perspective of the treating clinician.

Need to treat is at the discretion of the investigator, but there should be clinical equipoise about the use of eltrombopag vs standard treatment options (patients should not, in the opinion of the investigator, require concomitant therapy at time of enrollment).

- Treatment options include one of three standard therapies, (IVIg, steroids, or Anti-D). For example, if patient has previously shown no response to IVIg or steroids and is Rh-negative, patient would not be eligible for study.

- Patient population includes both:

1. Upfront treatment: Patient within 10 days of ITP diagnosis who has not received previous treatment OR

2. Treatment failure: Patients who have failed standard management (observation or treatment with one or more first-line agents)

- Failure of observation: no platelet recovery (>30 x 10^9/L) with observation >10 days from diagnosis, with need to treat

- Poor response to first-line agent (platelets remain <30 x10^9/L)

- Initial response to first-line agent, but response wanes and platelets fall below 30 x10^9/L

Exclusion Criteria:

- Severe bleeding: Buchanan Overall Grade 4 or 5 bleeding, or severe bleeding requiring emergent treatment at the discretion of the provider. (e.g., intracranial hemorrhage, pulmonary hemorrhage, bleeding with ongoing need for pRBC transfusion)

- Prior treatment with TPO-RA (eltrombopag or romiplostim)

- Known secondary ITP (due to lupus, CVID, ALPS)

- Known HIV (or history of HIV positivity) or Hepatitis C (screening not required if no clinical suspicion)

- Evans Syndrome: positive direct Coombs with evidence of active hemolysis (elevated lactate dehydrogenase (LDH) or reticulocyte count not attributable to recent treatment or bleeding)

- Any Malignancy

- History of stem cell transplant or solid organ transplant

- aspartate aminotransferase (AST) or ALT >2 x upper limit of normal (ULN)

- Total bilirubin >1.5 × ULN

- Subjects with liver cirrhosis (as determined by the investigator)

- Creatinine >2.5 × ULN

- Known active or uncontrolled infections not responding to appropriate therapy

- On anticoagulation or anti-platelet agents

- Known thrombophilic risk factors. Exception: Subjects for whom the potential benefits of participating in the study outweigh the potential risks of thromboembolic events, as determined by the investigator.

- Baseline ophthalmic problems that may potentiate cataract development

- Impaired cardiac function, such as:

- Known prolonged QTc, with corrected QTc >450 msec

- Other clinically significant cardio-vascular disease (e.g., uncontrolled hypertension, history of labile hypertension),

- History of known structural abnormalities (e.g. cardiomyopathy).

- History or current diagnosis of cardiac disease indicating significant risk of safety for patients participating in the study such as uncontrolled or significant cardiac disease, including any of the following:

- Recent myocardial infarction (within last 6 months),

- Uncontrolled congestive heart failure,

- Unstable angina (within last 6 months),

- Clinically significant (symptomatic) cardiac arrhythmias (e.g., sustained ventricular tachycardia, and clinically significant second or third degree AV block without a pacemaker.)

- Long QT syndrome, family history of idiopathic sudden death, congenital long QT syndrome or additional risk factors for cardiac repolarization abnormality, as determined by the investigator.

- Known immediate or delayed hypersensitivity reaction to eltrombopag or its excipient.

- Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study. Women of childbearing potential (have achieved menarche) must have a negative serum or urine pregnancy test and agree to use basic methods of contraception (if sexually active) or maintain abstinence for the duration of the study. Basic contraception methods include:

- Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception

- Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment

- Male sterilization (at least 6 months prior to screening). The vasectomized male partner should be the sole partner for that subject

- Barrier methods of contraception: Condom or Occlusive cap. For the UK: with spermicidal foam/gel/film/cream/ vaginal suppository

- Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception. In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment.

- Male patients who are sexually active and do not agree to abstinence or to use a condom during intercourse while taking eltrombopag, and for 7 days after stopping treatment.

- History of alcohol/drug abuse

- Presence of a medical condition that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.

- Concurrent participation in an investigational study within 30 days prior to enrollment or within 5-half-lives of the investigational product, whichever is longer. Note: parallel enrollment in a non-therapeutic trial such as disease registry or biology study is permitted.

Other Eligibility Criteria Considerations All patients and/or their parents or legal guardians must sign a written informed consent (and assent when applicable)

- Patients and/or parents who are unable to read English at a grade 2 level will be excluded from the patient-reported outcome component of the study. They will not be excluded from all other aspects of the study

Gender: All

Minimum Age: 1 Year

Maximum Age: 18 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Jenny Despotovic, DO Principal Investigator Baylor College of Medicine/Texas Children's Hospital
Overall Contact

Last Name: Jenny Despotovic, DO

Phone: 832-822-4302

Email: [email protected]

Location
Facility: Status: Contact: Contact Backup:
Phoenix CHildren's Hospital | Phoenix, Arizona, 85016, United States Recruiting Joanna Gendreau, MD 602-933-0920 [email protected]
Arkansas Children's Hospital | Little Rock, Arkansas, 72202, United States Recruiting Shelley Crary, MD 501-364-4194 [email protected] Shelley Crary, MD Principal Investigator
UCSF Benioff Children's Hospital | San Francisco, California, 94158, United States Recruiting Kristin Shimano, MD 415-476-4901 [email protected] Kristin Shimano, MD Principal Investigator
University of Florida College of Medicine | Gainesville, Florida, 32610, United States Recruiting Vandy Black, MD 352-273-9120 [email protected] Vandy Black, MD Principal Investigator
Ann & Robert H. Lurie Children's Hospital of Chicago | Chicago, Illinois, 60611, United States Recruiting Alexis Thompson, MD 312-227-4834 [email protected] Alexis Thompson, MD Principal Investigator
Riley Hospital for Children-Indiana University | Indianapolis, Indiana, 46202, United States Recruiting Kerry Hege, MD 317-944-9684 [email protected] Kerry Hege, MD Principal Investigator
Boston Children's Hospital | Boston, Massachusetts, 02115, United States Recruiting Rachael Grace, MD 617-355-8246 [email protected] Rachael Grace, MD Principal Investigator
Columbia University Irving Medical Center | New York, New York, 10032, United States Recruiting Cindy Neunert, MD 212-305-9770 [email protected] Cindy Neunert, MD Principal Investigator
Weill Cornell Medical College | New York, New York, 10065, United States Recruiting Shipra Kaiker 212-746-3400 [email protected] Shipra Kaiker, MD Principal Investigator
Duke University Medical Center | Durham, North Carolina, 27710, United States Recruiting Jennifer Rothman, MD 919-684-3401 [email protected] Jennifer Rothman, MD Principal Investigator
Nationwide Children's Hospital | Columbus, Ohio, 43205, United States Recruiting Melissa Rose, MD 614-722-3551 [email protected] Meilssa Rose, MD Principal Investigator
The Children's Hospital of Philadelphia | Philadelphia, Pennsylvania, 19104, United States Recruiting Michele Lambert, MD 215-590-4667 [email protected] Michele Lambert, MD Principal Investigator
Texas Children's Hospital | Houston, Texas, 77030, United States Recruiting Jenny Despotovic, DO 832-822-4302 [email protected] Jenny Despotovic, DO Principal Investigator
Location Countries

United States

Verification Date

October 2020

Responsible Party

Type: Principal Investigator

Investigator Affiliation: Baylor College of Medicine

Investigator Full Name: Jenny Despotovic

Investigator Title: Associate Professor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Eltrombopag

Type: Experimental

Description: Patients randomized to eltrombopag will be treated for 12 weeks, with the possibility to continue therapy for up to 1 year depending on response.

Label: Standard first-line therapy

Type: Active Comparator

Description: Subjects randomized to the standard therapy arm will receive one of three treatments at the discretion of the treating physician. Patients who previously failed standard management prior to study entry must be treated with a different agent than their original failed agent. e.g. Patient who failed steroids could receive either IVIg or anti-D if randomized to the standard treatment arm. Standard therapy will be administered as commercially available drug. Investigator may choose amongst the following: IVIg: IVIG 1 g/kg x1 (no steroids for pre-medication or adjunctive therapy) Steroids: Prednisone/Prednisolone 4 mg/kg/day (Max 120 mg/day) x 4 days Rho(D) Immune Globulin: Anti-D globulin 75 mcg/kg x1 (no steroids for pre-medication or adjunctive therapy)

Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov