A Study of Romiplostim to Prevent Low Platelet Counts in Children and Young Adults Receiving Chemotherapy for Solid Tumors

A Single Arm Open-Label Pilot Study of Prophylactic Romiplostim Use Compared to Benchmark Rate in the Prevention of Chemotherapy Induced Thrombocytopenia in Pediatric Solid Tumors Patients Undergoing Myelosuppressive Chemotherapy

The purpose of this study is to find out whether romiplostim can help prevent low platelet counts caused by N8 or EFT chemotherapy, reduce the number of platelet transfusions required during chemotherapy, and prevent treatment delays due to low platelet counts.

Study Overview

• Status: Terminated
• Conditions: Solid Tumor; Solid Carcinoma; Solid Tumor, Childhood
• Intervention / Treatment: Drug: Romiplostim

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
    • Middletown, New Jersey, United States, 07748
      • Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
    • Montvale, New Jersey, United States, 07645
      • Memorial Sloan Kettering Bergen (Limited Protocol Activities)
  • New York
    • Commack, New York, United States, 11725
      • Memorial Sloan Kettering Cancer Center @ Suffolk - Commack (Limited Protocol Activities)
    • Harrison, New York, United States, 10604
      • Memorial Sloan Kettering Westchester (Limited Protocol Activities)
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • Uniondale, New York, United States, 11553
      • Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Documented diagnosis of a primary solid tumor. Patients must have histological verification of malignancy at MSKCC.
• Male and female patients aged 1-21 years with a primary solid tumor undergoing treatment with the pre-defined chemotherapy regimens of EFT, MAP, D9803. Prior to enrollment patient could have been undergoing induction therapy with a similarly myelosuppressive regimen as long as they will be continuing with EFT, MAP, D9803 at the time of study enrollment.
• Patients undergoing treatment with MAP chemotherapy w ho have had ≥ 1 platelet transfusion during induction stage of treatment.
• Total Bilirubin (sum of conjugated + unconjugated) ≤ 3 times institutional upper limit of normal (ULN) for age and ALT/AST ≤ 3 times institutional ULN for age.

• Normal cardiac function:

  • Shortening fraction greater than or equal to 28% by echocardiogram OR Left ventricular ejection fraction (LVEF) greater than or equal to 50% on technetium- 99m pertechnetate radionuclide cineangiography (MUGA) or echocardiogram.
  • Screening ECG with corrected QT (QTc) interval of < 470 msec.
  • Timing of cardiac assessment: We will utilize the most recent EKG/ECHO when assessing cardiac function. See section 9.0 for additional details.
• Adequate renal function, defined as an estimated Creatinine Clearance or GFR >40ml/min or an normal creatine for age (see below)

Serum Creatinine by age:

Age (years) <6: Maximum Serum Creatinine (mg/dL), Male 0.8, Female 0.8 Age (years) 6 to <10: Maximum Serum Creatinine (mg/dL), Male 1, Female 1 Age (years) 10 to <13: Maximum Serum Creatinine (mg/dL), Male 1.2, Female 1.2 Age (years) 13 to <16: Maximum Serum Creatinine (mg/dL), Male 1.5, Female 1.4 Age (years) >16: Maximum Serum Creatinine (mg/dL), Male 1.7, Female 1.4

These threshold creatine values were derived from the Scwartz formula estimating GFR, utilizing child length and statured published by the CDC.

Exclusion Criteria:

• Patients with history of hematologic malignancies or allogenic/autogenic stem cell transplant.

• Patients with a currently known predisposition to a myeloid stem cell disorder, myeloid leukemia, and/or bone marrow failure syndrome including, but not limited to:

  • Aplastic anemia
  • Ataxia telangiectasia
  • Bloom syndrome
  • Congenital amegakaryocytic thrombocytopenia
  • Cyclic neutropenia
  • Diamond Blackfan anemia
  • Dyskeratosis congenita
  • Familial AML/MDS syndromes (including ANKRD26, CEBPA, DDX41, ETV6, GATA2, RUNX1, SRP72)
  • Fanconi anemia
  • Kostmann disease
  • Li-Fraumeni syndrome
  • Neurofibromatosis
  • Nijmegen breakage syndrome
  • Noonan syndrome
  • Paroxysmal nocturnal hemoglobinuria
  • Pearson syndrome
  • Poland syndrome
  • Rothmund-Thomson syndrome
  • Severe congenital neutropenia
  • Thrombocytopenia absent radii syndrome
  • Trisomy 8
  • Trisomy 21
  • WHIM syndrome
  • Wiskott Aldrich syndrome
  • Xeroderma pigmentosa
• Secondary malignancy in the past 5 years.
• Patients who have previously undergone up-front chemotherapy and have relapsed or progressed through therapy.
• Patients who have received 4 or more cycles of induction chemotherapy for their current malignancy prior to time of enrollment.
• Previous use of romiplostim, eltrombopag, recombinant human TPO, or any other TPO receptor agonist, or any investigational platelet producing agent.
• Patients receiving other investigational agents are not eligible for study entry.

History of uncontrolled arrhythmias, clinically significant electrocardiogram (ECG) abnormalities, active heart failure or pericardial disease.

• Patients with current or prior venous thrombotic event or arterial thrombotic event at time of enrollment will be ineligible for this study.
• Pregnant women/lactating mothers.
• Patients unwilling to use effective contraception method, which includes abstinence.
• Patients with an inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Pediatric Participants; Male and female patients aged 1-21 years with a primary solid tumor undergoing treatment with the pre-defined chemotherapy regimens of EFT, MAP or D9803.

Drug: Romiplostim; Participants will receive weekly doses of romiplostim, beginning with cycle 4. The initial romiplostim dose will be 10 mcg/kg, and subsequent doses w ill vary based on chemotherapy regimen for a target of platelet count > 75,000- 200,000/mcL. Participants will continue romiplostim until completion of MAP or D9803, as defined above. Maximum romiplostim dose is 10 mcg/kg. Participants will be followed until 6 months after the last dose of romiplostim.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Number of Platelet Transfusions During the Studied Portions of the EFT or D9803 Cycles	The primary purpose of this study is to evaluate whether romiplostim administration can decrease the total number of platelet transfusions required during the treatment courses of EFT or D9803 when compared to the benchmark rate.	up to 6 months

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Investigators: Principal Investigator: Michael Ortiz, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2020
• Primary Completion (Actual): March 29, 2023
• Study Completion (Actual): March 29, 2023

Study Registration Dates

• First Submitted: December 11, 2020
• First Submitted That Met QC Criteria: December 11, 2020
• First Posted (Actual): December 17, 2020

Study Record Updates

• Last Update Posted (Actual): November 18, 2023
• Last Update Submitted That Met QC Criteria: October 31, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Memorial Sloan Kettering Cancer Center; Solid tumor; romiplostim; primary solid tumor; Solid tumor, childhood; Childhood solid tumor; Pediatric Solid Tumors; 20-467
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: 20-467

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No