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

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT04671901

Collaborator

(none)

Enrollment

Locations

Arm

Anticipated Duration (Months)

4.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumor Solid Tumor, Childhood Solid Carcinoma	Drug: Romiplostim	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Dec 10, 2020

Anticipated Primary Completion Date :

Dec 10, 2022

Anticipated Study Completion Date :

Dec 10, 2022

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Total number of platelet transfusions during the studied portions of the EFT or D9803 cycles [up to 6 months]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 21 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memoral Sloan Kettering Basking Ridge (Limited Protocol Activities)	Basking Ridge	New Jersey	United States	07920
2	Memoral Sloan Kettering Monmouth (Limited Protocol Activities)	Middletown	New Jersey	United States	07748
3	Memorial Sloan Kettering Bergen (Limited Protocol Activities)	Montvale	New Jersey	United States	07645
4	Memorial Sloan Kettering Cancer Center @ Suffolk - Commack (Limited Protocol Activities)	Commack	New York	United States	11725
5	Memoral Sloan Kettering Westchester (Limited Protocol Activities)	Harrison	New York	United States	10604
6	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
7	Memorial Sloan Kettering Nassau (Limited Protocol Activities)	Uniondale	New York	United States	11553