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

Solid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04671901
• Other study ID #: 20-467
• Status: Terminated
• Phase: Phase 2
• Start date: December 10, 2020
• Est. completion date: March 29, 2023

Study information

• Verified date: March 2023
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: March 29, 2023
• Est. primary completion date: March 29, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 21 Years

Eligibility

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.

Related Conditions & MeSH terms

• Neoplasms
• Solid Carcinoma
• Solid Tumor
• Solid Tumor, Childhood

Intervention

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.

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)	Basking Ridge	New Jersey
United States	Memorial Sloan Kettering Cancer Center @ Suffolk - Commack (Limited Protocol Activities)	Commack	New York
United States	Memorial Sloan Kettering Westchester (Limited Protocol Activities)	Harrison	New York
United States	Memorial Sloan Kettering Monmouth (Limited Protocol Activities)	Middletown	New Jersey
United States	Memorial Sloan Kettering Bergen (Limited Protocol Activities)	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Memorial Sloan Kettering Nassau (Limited Protocol Activities)	Uniondale	New York

Sponsors (1)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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

External Links

•   Memorial Sloan Kettering Cancer Center